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CELLULAR AND MOLECULAR MEDICINE

2010 Annual Report

“Cell and Molecular Biology, Genetics, and Genomics

for Understanding Human Disease”

Cellular and Molecular Medicine East

The Palade Laboratories

Skaggs School of Pharmacy Leichtag Biomedical Research Natural Sciences Building

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Message from the Chair

This second Annual Report of the Department of Cellular and Molecular Medicine (CMM) highlights achievements and key events in 2010.

The great cell biologists of the 19th century, including Rudolph Virchow, the German physician widely known as the father of pathology, and the French physiologist Claude Bernard established the pivotal idea that individual cells function autonomously, while being part of the whole organism. Virchow added in his famous book Cellular Pathology that "All diseases are reducible to active or passive disturbances in cells." And more than 50 years ago E. B. Wilson proposed that "The key to every biological problem must finally be sought in the cell." CMM continues its course in following in those traditions. Cell and molecular biology, coupled with biochemistry and structural biology, has become the central core of Biomedical Research, with direct impact on clinical medicine.

Stem cell biology, at the forefront of much of recent excitement linking biology and medicine, rightfully is anchored at UCSD within CMM. Consistent with this, recent growth in CMM, partnered with Larry Goldstein (Professor in CMM and the Director of the UCSD Stem Cell Center), has emphasized stem cell biology. In the past three years growth has included Gene Yeo, Alysson Muotri, Maike Sander, and David Traver. In 2010, we were very pleased to have recruited George Sen (who arrived in December) as a new Assistant Professor. Sen’s interests are in mechanisms that govern epidermal stem cell self-renewal and differentiation, especially epigenetic regulators that he has identified with modern genomic approaches.

CMM also has a central focus on the explosive advances in the last decade in tools of genetics and genomics. CMM Professors Al La Spada and Bruce Hamilton are leaders of UCSD’s Institute of Genomic Medicine. Already with the most concentrated focus at UCSD in genetics and genomics – including Professors Chris Glass (recruited in 1990), Xiang-Dong Fu (recruited in 1992), Richard Kolodner (recruited in 1997) and Bing Ren (recruited in 2001), Associate Professor Bruce Hamilton (recruited in 1997) and Professor Al La Spada (recruited in 2009), we successfully recruited Assistant Professor Jonathan Sebat (who joined us in December, 2009). Sebat, who has made field leading discoveries of copy number variation in autism and schizophrenia, has continued his blazing pace of discovery. And at a very young age has been named the first Chief of the Beyster Center for Molecular Genomics of Neuropsychiatric Diseases at UCSD.

Areas classically within cell biology remain a core of CMM, which was very pleased in 2010 to recruit Kevin Corbett as its newest Assistant Professor. Corbett, an accomplished structural biologist now with Steve Harrison’s group at Harvard Medical School, is now focused on the structure of the centromere and its attached kinetochore. CMM believes that he adds an important new dimension to ongoing interests in centromeres, mitosis and cytokinesis, and synergies with current CMM faculty (especially Karen Oegema, Arshad Desai and me) are anticipated. Corbett is expected to join the department in summer, 2011.

With the newest additions, the Department now stands at over 325 (25 primary faculty, 10 faculty with primary appointments in other departments, 115 postdoctoral scholars, 47 graduate students, 81 research staff, and 49 administrative staff). We have major roles in teaching in both the medical student and graduate student curricula, especially in molecular cell biology and genetics and genomics. We continue to host what we believe to be the most vibrant seminar series at UCSD in the biological/medical disciplines.

I will close by highlighting three key events of 2010. First, the George Palade Symposium – held on January 28, 2010 – celebrated George’s long contributions to science and UCSD. Second, CMM – especially Christopher Glass and Connie Holm – played a major role in the redesign of the Medical School Curriculum, the first major overhaul in the Medical School’s 42 year history. Long overdue, CMM strongly supported updating the curriculum to better prepare our students for medicine in the twenty first century. Third, and perhaps the most remarkable outcome of 2010, CMM’s entrepreneurial faculty have been even more successful in competing for grant support despite the United States’ and the University of California’s continuing financial crisis. Indeed, CMM faculty increased outside grant support by an amazing 39% (from $26 million to $36 million). !

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Table of Contents

Message from the Chair 1

News & Highlights from 2010 3

CMM Faculty 8

Faculty Honors & Awards 10

Overview 11

The 2010 CMM Faculty 12

New and Ongoing Research Initiatives 29

CMM Contracts and Grant 2010 32

Exceptional Awards to CMM Faculty 32

CMM Faculty compete for $4 million (year 2) from President Obama’s ARRA Stimulus 34

CMM Faculty Research Funding 35

2010 CMM/LICR Seminar Series 36

CMM Staff 38

Business Office Operations

Postdoctoral Fellows in CMM 39

Graduate Students in CMM 43

Photos 45

George Palade Symposium 45

CMM Faculty Dinner reception 48

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News & Highlights from 2010

• The George Palade Symposium: celebrating the life and accomplishments of CMM’s Founder, Nobel Laureate George Palade, January 28, 2010

• CMM’s external grant funding jumps 39% in 2010: CMM faculty awarded $4 million for 2nd year from Obama’s ARRA Stimulus

• Christopher Glass, Connie Holm, Al La Spada and Don Cleveland lead CMM’s contribution to complete overhaul of the medical school curriculum!

• CMM’s Xiang-Dong Fu, Peter Novick and Yishi Jin are three of seven UCSD faculty elected Fellows of the American Association for the Advancement of Science (AAAS)

• CMM’s Jeff Esko receives an honorary degree from the Univ. of Uppsala

• Alysson Muotri’s team creates model of autistic neurons from induced pluripotent stem cells !

• George Sen and Kevin Corbett: New faculty recruited to CMM

• Don Cleveland’s group initiates a gene silencing clinical trial to treat inherited ALS

• Construction of UCSD’s Stem Cell Program, headed by CMM’s Larry Goldstein, is highlighted on CBS Evening News

• Team lead by CMM’s Alysson Muotri is awarded $5.8 million from CIRM for early stem cell translational research studies

• Arshad Desai and Karen Oegema join CMM’s Professorial Ranks

• CMM’s Jonathan Sebat named the First Chief of the Beyster Center for Molecular Genomics of Neuropsychiatric Diseases at UCSD

• Maike Sander along with Karl Willert awarded $5 million for diabetes research from the Beta Cell Biology Consortium!

• Larry Goldstein and Don Cleveland lead an $11 million effort funded by CIRM to develop a stem cell-derived, cell replacement therapy for ALS

• Ajit Varki’s career accomplishments highlighted by the American Society for Biochemistry and Molecular Biology (ASBMB) !

• CMM’s Al La Spada identifies NnA proteins to play central role in catastrophic neuronal death in mice, flies and perhaps people

• CMM’s Pascal Gagneux featured in Atlantic Monthly for discoveries in fertility!

• Alysson Muotri’s team identifies autistic neurons with jumping genes in the brain!

• Christopher Glass identifies cholesterol-lowering statins boost bacteria-killing cells!

• CMM’s Larry Goldstein authors a new book: “Stem Cells for Dummies”

• Al La Spada’s efforts demonstrate mutations in beta-synuclein promote neurodegeneration!

• David Traver identifies dendritic antigen-presenting cells in zebrafish!

• Arshad Desai and Karen Oegema identify specialized chromosome segregation pathway in eggs !

• Shankar Subramaniam named Distinguished Scientist at the San Diego Supercomputer center, June 2010

• CIRM Awards $1.5 Million grant to Alysson Muotri for development of autistic neuron models!

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THE GEORGE PALADE SYMPOSIUM

On January 28, 2010, the School of Medicine and the Department of Cellular and Molecular Medicine (CMM) hosted a full day event commemorating the life and work of George Palade, former Dean for Scientific Affairs and co-founder of CMM. The program included three Nobel laureates Gunter Blobel of Rockefeller University; Roger Kornberg of Stanford, and Joseph Goldstein of Univ. of Texas-Southwestern, as well as Peter Walter of UCSF; Randy Schekman of UC-Berkeley; former CMM faculty member Scott Emr, now of Cornell; James Spudich of Stanford; and our own Peter Novick, the founding holder of the George Palade Endowed Chair. Many former students, postdocs, colleagues and personal friends of George Palade and Marilyn Farquhar were in attendance. A video of the presentations and reception photos are on the CMM website.

CMM’S EXTERNAL GRANT FUNDING JUMPS 39% IN 2010: CMM FACULTY AWARDED $4 MILLION FROM OBAMA’S ARRA STIMULUS

Despite a declining funding climate, CMM’s entrepreneurial faculty successfully increased the department’s external funding by $10 million, a whopping 39%. Exceptional awards include a $11 million CIRM Disease Team grant, $5.8 million CIRM stem cell award, and $5 million from the Beta Cell Biology Consortium for Type 1 diabetes. Included in this 39% increase in overall external funding to CMM faculty in 2010 were $4 million from President Obama’s American Recovery and Reinvestment Act (ARRA) stimulus funding,

CHRISTOPHER GLASS, CONNIE HOLM, AL LA SPADA AND DON CLEVELAND LED CMM’s CONTRIBUTION TO A COMPLETE OVERHAUL OF THE MEDICAL SCHOOL CURRICULUM

CMM played a significant role in the complete restructuring of the Medical school curriculum, marking the first major curricular revision since the founding of the medical school 42 years ago. The new curriculum features a greatly increased emphasis on active learning and independent study, preparing students for careers in which they must constantly keep abreast of rapidly appearing medical advances. An emphasis on clinical relevance provides a context

for learning, and a foundation of modern biology provides a framework from which to interpret new drug mechanisms and medical discoveries. Connie Holm, along with Don Cleveland, developed the cellular biology/molecular biology thread, and Al La Spada led the overhaul of the genetics/genomics thread. Connie Holm was Course Director for “Foundations of Human Biology,” the first course of the new curriculum and one in which cell biology, molecular biology, and genetics were integrated in a meaningful clinical context. Lecture hours were greatly reduced and replaced with small group interactions. Problem-based learning sessions allowed small teams of students to work through clinical scenarios, identifying gaps in their own knowledge and working collaboratively to rectify them. In a siminar vein, Christopher Glass directed the development of the new Endocrinology, Reproduction and Metabolism Course. Part one of the course is given to first year medical students and second year pharmacy students, using lectures, small groups and clinically oriented problem-based learning exercises to present basic principles of hormone action, reproduction and metabolism. Part two of the course is given to second year medical students and third year pharmacy students and focuses on diseases of the endocrine and reproductive systems.

CMM’S XIANG-DONG FU, PETER NOVICK AND YISHI JIN ARE THREE OF SEVEN UCSD FACULTY ELECTED FELLOWS OF THE AMERICAN ASSOCIATION FOR THE ADVANCEMENT OF SCIENCE (AAAS)

Professors Xiang-Dong Fu, Yishi Jin and Peter Novick became CMM’s newest Fellows of the American Association for the Advancement of Science (AAAS). AAAS members are elected by their colleagues for “efforts toward advancing science applications that are deemed scientifically or socially distinguished.” AAAS is the world’s largest general scientific society. CMM was delighted this year that three of the seven faculty elected from UCSD are from CMM.

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CMM’S JEFF ESKO RECEIVES AN HONORARY DEGREE FROM UNIVERSITY OF UPPSALA

Jeff Esko was presented with the honorary Doctor of Medicine (Honoris causa) degree from the University of Uppsala, Sweden.

ALYSSON MUOTRI’S TEAM CREATES MODEL OF AUTISTIC NEURONS FROM INDUCED PLURIPOTENT STEM CELLS

In work published in Cell in November, Alysson Muotri and his team used induced pluripotent stem cells from patients with Rett syndrome to create functional neurons that provide the first human cellular model for studying the development of autism spectrum disorder (ASD) and could be used as a tool for drug screening, diagnosis and personalized treatment.

GEORGE SEN AND KEVIN CORBETT: NEW FACULTY RECRUITED TO CMM

CMM undertook a national search and successfully recruited two new Assistant Professors. George Sen, recruited from Stanford in conjunction with the Division of Dermatology in the Department of Medicine, joined us from Stanford in December, 2010. Recruitment of George, with his pioneering work in genomics and epigenetics of skin stem cells, reinforces CMM’s commitment to genetics and genomics and UCSD’s expanded stem cell program. Kevin Corbett, now with Steve Harrison in Biological Chemistry at Harvard, has been recruited jointly by CMM and the Ludwig Institute for Cancer Research. Kevin’s interests, use of structural biological approaches to understand centromeres and their associated kinetochores, complement the strengths of CMM’s Oegema, Desai and Cleveland. Kevin is scheduled to arrive at UCSD in the summer of 2011.

DON CLEVELAND’S GROUP INITIATES A GENE SILENCING CLINICAL TRIAL TO TREAT INHERITED ALS

Don Cleveland’s team, in partnership with Isis Pharmaceuticals, initiated a Phase I clinical trial using a gene silencing therapy for treatment of an inherited form of the fatal motor neuron disease Amyotrophic Lateral Sclerosis (ALS), more familiarly known as Lou Gehrig’s disease. Cleveland’s group had previously demonstrated that the disease causing mutation in

superoxide dismutase produces an acquired toxicity of the mutant protein, while reduction in normal levels is well tolerated, at least in mice. Thus, the strategy now in trial is infusion into the cerebral spinal fluid of an antisense DNA oligonucleotide to suppress synthesis of the mutant protein. This trial represents the first antisense drug designed to inhibit the production of a gene within the nervous system.

CONSTRUCTION OF UCSD’S STEM CELL PROGRAM, HEADED BY CMM’S LARRY GOLDSTEIN, IS HIGHLIGHTED ON CBS EVENING NEWS

In March 2010, the Sanford Consortium for Regenerative Medicine, headed by Larry Goldstein, broke ground for the 145,000 square foot building on land owned by UC San Diego. The four organizations that will do research in what has been dubbed a “collaboratory” are UCSD, Salk, Sanford-Burnham and the Scripps Research Institute. Billed as the first center of its kind in California, the stem cell facility was highlighted on the CBS Evening News. It will include a 16,000 square foot vivarium and an enclosed area for observing plant and animal life for research. It will also have a 4,000 square foot auditorium, laboratories, and imaging centers.

TEAM LEAD BY ALYSSON MUOTRI AND CATRIONA JAMIESON RECEIVES $5.8 MILLION AWARD FROM CIRM FOR EARLY TRANSLATIONAL STEM CELL RESEARCH STUDIES

Two scientists at the University of California, San Diego School of Medicine – CMM’s Alysson Muotri, PhD and Catriona Jamieson, MD, PhD – have received $5.8 million in grants from the California Institute for Regenerative Medicine (CIRM) for stem cell research. The grants are part of $67 million in Early Translation II Awards announced by CIRM today, which are designed to move research from lab to the clinic.

ARSHAD DESAI AND KAREN OEGEMA JOIN CMM’S PROFESSORIAL RANKS

Arshad Desai and Karen Oegema were promoted to the rank of full professor in July 2010. Both received recognition for their outstanding contributions to understanding cytokinesis and chromosome segregation.

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CMM’S JONATHAN SEBAT NAMED THE FIRST CHIEF OF BEYSTER CENTER FOR MOLECULAR GENOMICS OF NEUROPSYCHIATRIC DISEASES AT UCSD

Jonathan Sebat, Assistant Professor in CMM, was named the first Chief of the Beyster Center for Molecular Genomics of Neuropsychiatric Diseases at UCSD. He will head the new Center focused on advancing the understanding and management of mental illness.

MAIKE SANDER AWARDED $5 MILLION FOR DIABETES RESEARCH FROM THE BETA CELL BIOLOGY CONSORTIUM

Maike Sander, MD, Associate Professor of CMM and Pediatrics, was awarded nearly $5 million grant from the Beta Cell Biology Consortium to develop a stem cell therapy for type 1 diabetes. The grant is shared with Karl Willert, PhD, CMM Assistant Professor and Director of the UCSD Human Stem Cell Core Facility.

LARRY GOLDSTEIN AND DON CLEVELAND LEAD AN $11 MILLION EFFORT FUNDED BY CIRM TO DEVELOP A STEM CELL DERIVED, CELL REPLACEMENT THERAPY FOR ALS

In June 2010, Larry Goldstein and Don Cleveland, along with Martin Marsala of Anesthesiology and Sam Pfaff of the Salk Institute, have received an $11 million award from the California Institute of Regenerative Medicine for the development of a cell replacement therapy for ALS. The approach will use spinal injection of stem cell-derived precursors of astryocytes, essential support cells of the motor neurons whose death leads to the fatal paralysis characteristic of ALS.

AJIT VARKI’S CAREER HIGHLIGHTED BY ASBMB

In its Science Focus section, the American Society for Biochemistry and Molecular Biology (ASBMB) highlighted the career accomplishments of Ajit Varki. The article complemented Varki on how his use of biochemistry, molecular biology and genetics of sialic acids has answered broader questions about human origins, disease and evolution.

LA SPADA IDENTIFIES NnA PROTEINS TO PLAY CENTRAL ROLE IN CATASTROPHIC NEURON DEATH IN MICE, FLIES AND PERHAPS PEOPLE

In work published in Neuron, CMM Professor Al La Spada’s team identified a key player in the dramatic loss of neurons in mice and fly models, a discovery that could help illuminate the role of mitochondrial dysfunction in human neurodegenerative disorders, such as Parkinson’s disease. They found that the loss of Nna proteins caused by a defective Nna gene alters the energy flow within nerve cells, resulting in severe mitochondrial abnormalities that may be linked to massive cell death.

PASCAL GAGNEUX FEATURED IN ATLANTIC MONTHLY FOR RESEARCH IN FERTILITY

The work of Pascal Gagneux, Assistant Professor in CMM and Associate Director of the Center for Academic Research and Training in Anthropology (CARTA), was featured in an article in Atlantic Monthly. The article focused on his analysis of the differences between human and chimp sperm - especially the sugars that adorn the sperms’ surfaces and let them bind to cells in the walls of the uterus or a fallopian tube – as a means to unlock one of the riddles of human infertility: does sperm sometimes have components that undermine its ability to fertilize an egg.

ALYSSON MUOTRI’S TEAM IDENTIFIES AUTISTIC NEURONS WITH JUMPING GENES IN THE BRAIN

With few exceptions, jumping genes - restless bits of DNA that can move freely about the genome - are forced to stay put. In patients with Rett syndrome, however, a mutation in the MeCP2 gene mobilizes so-called L1 retrotransposons in brain cells, reshuffling their genomes and possibly contributing to the symptoms of the disease when they find their way into active genes. Findings by Alysson Muotri’s team, along with colleagues at the Salk Institute and published in the November in Nature, not only explain how a single mutation can cause the baffling variability of symptoms typical of Rett syndrome, but also shed new light on the complexity of molecular events that underlie psychiatric disorders such as autism and schizophrenia.

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GLASS’ TEAM IDENTIFIES THAT CHOLESTEROL-LOWERING STATINS BOOST BACTERIA-KILLING CELLS

Widely prescribed for their cholesterol-lowering properties, recent clinical research indicates that statins can produce a second, significant health benefit: lowering the risk of severe bacterial infections such as pneumonia and sepsis. A new explanation for these findings has been discovered by Christopher Glass, MD, PhD, Professor of CMM and Victor Nizet, MD, Professor of Pediatrics and Pharmacy. Their teams found that phagocytes (white blood cells that kill and ingest harmful bacteria, foreign particles and dead or dying cells) became more effective after being exposed to statins.

CMM’S LARRY GOLDSTEIN AUTHORS A NEW BOOK: “STEM CELL FOR DUMMIES”

Larry Goldstein, along with his co-author Meg Schneider, published a new book, “Stem Cells for Dummies” in March 2010. Drawing on his scientific expertise, clinical web sites, input from colleagues and real world examples, Goldstein and Schneider converted the scientific concepts underpinning current stem cell insights and approaches into simple English. The book is on sale nationwide.

LA SPADA’S EFFORTS DEMONSTRATE MUTATIONS IN BETA-SYNUCLEIN PROMOTE NEURODEGENERATION

Al La Spada, Professor of CMM and Associate Director of the Institute for Genomic Medicine, along with a team of scientists from Japan, created a new mouse model that confirms that mutations of a protein called beta-synuclein promote neurodegeneration. The discovery creates a new target for developing treatments of diseases like Parkinson’s and Alzheimer’s.

DAVID TRAVER IDENTIFIES DENDRITIC ANTIGEN PRESENTING CELLS IN ZEBRAFISH

Associate Professor of CMM David Traver, along with colleagues in UCSD’s Division of Biological Sciences, identified dendritic antigen-presenting cells in zebrafish. This discovery, published in the Proceedings of the National Academy of Science, opens the possibility that the tiny fish could become a new model for studying the complexities of the human immune system. aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

ARSHAD DESAI AND KAREN OEGEMA IDENTIFY SPECIALIZED CHROMOSOME SEGREGATION PATHWAY IN EGGS

Reporting in Nature Cell Biology last September, Karen Oegema and Arshad Desai, both Professors in CMM, discovered an unusual property of meiosis – cell division that produces reproductive cells in sexually reproducing organisms. The discovery of an “inside out” mechanism by which egg cell chromosomes separate from each other may shed light on mistakes made in chromosome distribution that can lead to Down syndrome, high miscarriage rates in humans, and the age-related decrease in fertility in human females.

SHANKAR SUBRAMANIAM NAMED DISTINGUISHED SCIENTIST BY THE SAN DIEGO SUPERCOMPUTER CENTER

Shankar Subramaniam, Adjunct Professor in CMM was named a Distinguished Scientist by the San Diego Super Computer Center (SDSC).

CIRM AWARDS $1.5 MILLION GRANT TO ALYSSON MUOTRI FOR DEVELOPMENT OF AUTISTIC NEURON MODELS

CIRM has awarded Alysson Muotri, Assistant Professor of CMM, nearly $1.5 million dollars to design a future drug-screening system for autism spectrum disorders (ASD) that employs human neurons. Muotri and colleagues are using induced pluripotent stem cells derived from skin cells taken from patients with autism spectrum disorders like Rett Syndrome to create “autistic” neurons. “These are experiments that have never been possible before,” said Muotri. “We hope they will help us better understand the causal molecular mechanisms of ASD, find possible biomarkers for the disease and identify specific therapeutic targets.”

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CMM Faculty !

Don W. Cleveland, Ph.D. Distinguished Professor and Chair Dual appointments in Medicine and Neurosciences Kevin Corbett, Ph.D. ! Assistant Professor Arshad Desai, Ph.D. Professor Investigator, Ludwig Institute for Cancer Research Jack Dixon, Ph.D. Distinguished Professor Dual appointments in Pharmacology and Chemistry & Biochemistry Steven F. Dowdy, Ph.D. Professor Investigator, Howard Hughes Medical Institute Jeffrey D. Esko, Ph.D. Professor Co-Director, Glycobiology Research and Training Center James R. Feramisco, Ph.D Professor Primary appointment in Medicine Marilyn G. Farquhar, Ph.D. Distinguished Professor Susan Ferro-Novick, Ph.D. Professor Investigator, Howard Hughes Medical Institute Xiang-Dong Fu, Ph.D. Professor Pascal Gagneux, Ph.D. Adjunct Assistant Professor Associate Director, Center for Academic Research & Training in Anthropogeny Gordon N. Gill, M.D. Professor Emeritus Dean of Science, School of Medicine Christopher K. Glass, M.D., Ph.D. Professor Dual appointment in Medicine

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Lawrence S. B. Goldstein, Ph.D. Distinguished Professor Director, UCSD Stem Cell Research Program Investigator, Howard Hughes Medical Institute Bruce A. Hamilton, Ph.D. Associate Professor Dual appointment in Medicine Stephen M. Hedrick, Ph.D. Distinguished Professor Dual appointment in the Division of Biological Sciences Yishi Jin, Ph.D. Professor Investigator, Howard Hughes Medical Institute Dual appointment in the Division of Biological Sciences Richard Kolodner, Ph.D. Distinguished Professor Investigator, Ludwig Institute for Cancer Research Dual appointment in Medicine Albert La Spada, M.D., Ph.D. Professor Dual appointment in Pediatrics Chief, Division of Pediatric Genetics Jonathan H. Lin, M.D., Ph.D. Assistant Professor Primary appointment in Pathology Alysson R. Muotri, Ph.D. Assistant Professor Dual appointment in Pediatrics Sanjay Nigam, M.D. Professor Dual appointments in Pediatrics and Medicine Peter Novick, Ph.D. Professor Karen Oegema, Ph.D. Professor Investigator, Ludwig Institute for Cancer Research Bing Ren, Ph.D. Professor Investigator, Ludwig Institute for Cancer Research Maike Sander, M.D. Associate Professor Primary appointment in Pediatrics

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Jonathan Sebat, Ph.D. Assistant Professor Dual appointment in Psychiatry George Sen, Ph.D. **

Assistant Professor Dual appointment in Medicine Deborah Spector, Ph.D. Distinguished Professor Dual appointment in Skaggs School of Pharmacy Shankar Subramaniam, Ph.D. Professor Primary appointment in Bioengineering

David Traver, Ph.D. Associate Professor Dual appointment in the Division of Biological Sciences Ajit P. Varki, M.D. Distinguished Professor Co-Director, Glycobiology Research and Training Center Director, Center for Academic Research & Training in

Anthropogeny Associate Dean, Physician-Scientist Training Primary appointment in Medicine Karl Willert, Ph.D. Assistant Professor in Residence Director, UCSD Human Embryonic Stem Cell Facility Eugene Yeo, Ph.D. Assistant Professor Huilin Zhou, Ph.D. Associate Professor Associate Investigator, Ludwig Institute for Cancer Research

** Joined CMM in December, 2010

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Faculty Honors & Awards DON W. CLEVELAND Elected Member, National Academy of Sciences Elected Member, American Academy of Arts & Sciences Elected Member, American Academy of Microbiology Elected Fellow, American Association for the Advancement

of Science ARSHAD DESAI Damon Runyon Scholar Early Career Award from the American Society for Cell

Biology JACK DIXON Elected Member, National Academy of Sciences Elected Member, American Academy of Arts & Sciences Elected Fellow, American Association for the Advancement

of Science Elected Member, Institute of Medicine MARILYN G. FARQUHAR Elected Member, National Academy of Sciences Elected Member, American Academy of Arts & Sciences E.B. Wilson Medalist, American Society for Cell Biology JAMES R. FERAMISCO Elected Member, American Society for Clinical

Investigation XIANG-DONG FU Elected Fellow, American Association for the Advancement

of Science, 2010 GORDON N. GILL Elected Member, American Academy of Arts & Sciences Elected Member, American Society for Clinical

Investigation CHRISTOPHER K. GLASS Elected Member, Association of American Physicians Elected Member, American Society for Clinical

Investigation LAWRENCE S. B. GOLDSTEIN Elected Member, American Academy of Arts & Sciences YISHI JIN Elected Fellow, American Association for the Advancement

of Science, 2010

RICHARD KOLODNER Elected Member, National Academy of Sciences Elected Member, American Academy of Arts & Sciences ALBERT LA SPADA Elected Member, American Society for Clinical

Investigation JONATHAN H. LIN American Society for Investigative Pathology Excellence in

Science Young Faculty Award ALYSSON R. MUOTRI NIH Director’s New Innovator Award Emerald Foundation Young Investigator Award SANJAY NIGAM Elected Member, Association of American Physicians Elected Member, American Society for Clinical

Investigation PETER NOVICK Elected Member, American Academy of Arts & Sciences Elected Member, American Academy of Microbiology Inaugural Recipient of the George Palade Endowed Chair Elected Fellow, American Association for the Advancement

of Science, 2010 KAREN OEGEMA Pew Scholar American Society for Cell Biology Outstanding Woman,

Junior Award MAIKE SANDER Grodsky Award, Basic Research Scientist Award in Diabetes

Research from the JDRF SHANKAR SUBRAMANIAM UCSD Faculty Excellence Award and Jacobs Endowed

Chair in Bioengineering AJIT P. VARKI Elected Member, Institute of Medicine Elected Member, American Academy of Arts & Sciences Elected Member, Association of American Physicians Elected Member, American Society for Clinical

Investigation GENE YEO Fellow, The Alfred P. Sloan Foundation

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CMM Faculty Overview of Research Interests CANCER BIOLOGY Don Cleveland Jack Dixon Steve Dowdy Jeffrey Esko Marilyn Farquhar James Feramisco Xiang-Dong Fu Pascal Gagneux Lawrence Goldstein Richard Kolodner Jonathan Lin Bing Ren Maike Sander Ajit Varki Karl Willert Huilin Zhou CELL CYCLE AND MITOSIS Don Cleveland Kevin Corbett Arshad Desai Steve Dowdy Karen Oegema Huilin Zhou CELLULAR AND MOLECULAR BASIS OF DISEASE Don Cleveland Steve Dowdy Jeffrey Esko Marilyn Farquhar James Feramisco Xiang Dong Fu Christopher Glass Lawrence Goldstein Bruce Hamilton Richard Kolodner Al La Spada Jonathan Lin Alysson Muotri Sanjay Nigam Bing Ren Maike Sander Jonathan Sebat Deborah Spector Ajit Varki Gene Yeo Huilin Zhou

DNA METABOLISM Richard Kolodner Alysson Muotri Huilin Zhou !DEVELOPMENTAL BIOLOGY Lawrence Goldstein Bruce Hamilton Yishi Jin Alysson Muotri Sanjay Nigam Maike Sander Karl Willert EVOLUTION Jeffrey Esko Pascal Gagneux Alysson Muotri Ajit Varki Gene Yeo GENE EXPRESSION AND REGULATION Jack Dixon Steven Dowdy Xiang Dong Fu Gordon Gill Christopher Glass Alysson Muotri Bing Ren Maike Sander George Sen Gene Yeo GENETICS AND GENOMICS Arshad Desai Susan Ferro-Novick Xiang Dong Fu Pascal Gagneux Christopher Glass Lawrence Goldstein Bruce Hamilton Yishi Jin Richard Kolodner Al LaSpada Alysson Muotri Peter Novick Bing Ren Maike Sander Jonathan Sebat George Sen Gene Yeo

GLYCOBIOLOGY Jeffrey Esko Pascal Gagneux Jonathan Lin Ajit Varki MEMBRANE TRAFFICKING Steven Dowdy Marilyn Farquhar Susan Ferro-Novick Gordon Gill Sanjay Nigam Peter Novick Ajit Varki NEUROSCIENCE Don Cleveland Lawrence Goldstein Bruce Hamilton Yishi Jin Al La Spada Jonathan Lin Alysson Muotri Jonathan Sebat Gene Yeo SIGNALING Steven Dowdy Marilyn Farquhar Susan Ferro-Novick Gordon Gill Christopher Glass Lawrence Goldstein Bruce Hamilton Stephen Hedrick Yishi Jin Jonathan Lin Sanjay Nigam Peter Novick Bing Ren Ajit Varki Karl Willert Huilin Zhou STEM CELLS Steven Dowdy Lawrence Goldstein Jonathan Lin Alysson Muotri Bing Ren Maike Sander George Sen Karl Willert Gene Yeo

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Don W. Cleveland, Ph.D. Chair, Cellular and Molecular Medicine Distinguished Professor of Cellular and Molecular Medicine, Neuroscience, and Medicine Investigator, Ludwig Institute for Cancer

Phone: (858) 534-7811 E-Mail: cmmchair@ucsd.edu Website: http://cmm.ucsd.edu/cleveland/Home.html

RESEARCH INTERESTS • Molecular genetics of centromeres and mammalian chromosome segregation • Molecular genetics of axonal growth and motor neuron disease

RESEARCH SUMMARY One focus of Dr. Don Cleveland's research is identifying mechanisms of chromosome segregation. This year they identified a phosphorylation switch essential to prevent chromosome missegregation. The microtubule motor CENP-E was shown to tow misaligned chromosomes to the spindle center after its phosphorylation by Aurora A/B kinases, thereby dislodging protein phosphastase 1 initially bound to it. After congression, CENP-E then locally delivers protein phosphastase 1, whose rebinding is essential for activation of the microtubule capture components of the centromeres on the newly congressed chromosomes. A second focus is on mechanisms underlying the motor neuron disease ALS. This year they demonstrated that motor neuron death in an inherited form arises from the disease causing mutant protein inhibition of ion conductance into mitochondria. Additionally, they initiated a clinical trial for this form of ALS, using a first-in-man approach exploiting antisense oligonucleotide infusion into the nervous system to lower expression of the disease causing mutant gene.

SELECTED PUBLICATIONS FROM 2010 1. Kim, Y., Holland, A.J., Lan, W. and Cleveland, D.W. 2010. Aurora kinases mediate chromosome congression through

regulation of CENP-E. Cell 142:444-455. 2. Israelson, A., Arbel, N., Da Cruz, S., Ilieva, H., Yamanaka, K., Shoshan-Barmatz, V. and Cleveland, D.W. 2010.

Misfolded mutant SOD1 directly inhibits VDAC1 conductance in a mouse model of inherited ALS. Neuron 67:575-587.

Arshad Desai, Ph.D. Professor of Cellular and Molecular Medicine Member, Ludwig Institute for Cancer Research

Phone: (858) 534-9698 E-Mail: abdesai@ucsd.edu Website: http://sandiego.licr.org/D_groups/d6_Chromosome-Biology.php

RESEARCH INTERESTS • Mechanisms that segregate chromosomes during cell division • Composition of kinetochores

RESEARCH SUMMARY The Desai group is focused on understanding the mechanisms that segregate chromosomes during cell division. Specifically, the group identified the components and pathways of their assembly into the kinetochores which connect chromosomes to spindle microtubules during cell division. The laboratory has combined functional genomics with proteomics and in vitro reconstitutions to define the conserved protein network that provides the core microtubule-binding activity at kinetochores. The group is also studying the mechanisms that specify kinetochore formation at a localized site on chromosomes, which involves formation of specialized chromatin containing a centromeric histone H3 variant. In the past year, the labs’ efforts have revealed the key step involved in silencing the checkpoint pathway that ensures the fidelity of chromosome segregation (1) and described a new mechanism that operates to segregate chromosomes during meiosis in egg cells (2).

SELECTED PUBLICATIONS FROM 2010 1. Gassmann R, Holland A, Varma D, Wan X, Cleveland D, Oegema K, Salmon ED, Desai A. 2010. Removal of Spindly

from microtubule-attached kinetochores controls spindle checkpoint silencing in human cells. Genes Dev. 24:957-71. 2. Dumont J, Oegema K, Desai A. 2010. A kinetochore-independent mechanism drives anaphase chromosome separation

during acentrosomal meiosis. Nat Cell Biol. 12:894-901.

Awards and Honors Member, National Academy of Sciences Member, American Academy of Arts and Sciences Fellow, American Association for Advancement of

Science Member, American Academy of Microbiology

Awards and Honors Damon Runyon Scholar Early Career Award from the American Society for Cell

Biology, 2008

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Jack Dixon, Ph.D. Distinguished Professor of Cellular and Molecular Medicine, Pharmacology, Chemistry and Biochemistry Vice President and Chief Scientific Officer of the Howard Hughes Medical Institute

Phone: (858) 822-0653 E-Mail: jedixon@ucsd.edu Website: http://cmm.ucsd.edu/Lab_Pages/Dixon/

RESEARCH SUMMARY Dr. Dixon’s laboratory works on a family of proteins called phosphotases that play a key role in cellular response to molecular signals. This work has helped define a broad range of signaling events, including the role of specific phosphotases in cancer, tumor suppression, and in cellular response to bacterial toxins.

SELECTED PUBLICATIONS

1. Mitchell, D.A., Lee, S.W., Pence, M.A., Markley, A.M., Limm, J.D., Nizet, V., and Dixon, J.E. 2009. Structural and functional dissection of the heterocyclic peptide cytotoxin streptolysin S. J. Biol. Chem. 284: 13004-13012.

2. Xiao, J., Worby, C.A., Mattoo, S., Sankaran, B., and Dixon, J.E. 2010. Structural basis of Fic-mediated adenylylation. Nat. Struct. Mol. Biol. 17:1004-10.

Steven F. Dowdy, Ph.D. Professor of Cellular and Molecular Medicine Investigator, Howard Hughes Medical Institute Phone: (858) 534-7772 E-Mail: sdowdy@ucsd.edu Website: http://cmm.ucsd.edu/Lab_Pages/Dowdy/

RESEARCH INTERESTS

• Regulation of G1 cell cycle progression, focused on mechanisms that activate the cell cycle machinery in cancer • TAT Peptide Transduction Domain (PTD)-mediated delivery of novel macromolecular anticancer siRNA therapeutics

RESEARCH SUMMARY

Dr. Steven Dowdy’s research group focuses on the cell cycle and transition across the G1 restriction point into the late G1 phase, that requires the coordinated efforts of multiple cyclin:Cdk complexes and an increased metabolism. The retinoblastoma tumor-suppressor (RB) targets E2F family member transcription factors and represses E2F-dependent transcription. Transition across the restriction point irrevocably commits a cell to continue through the rest of the cell cycle. This key growth regulatory checkpoint balances the appropriate requisite level of metabolism with growth factor stimulation. Dr. Dowdy’s lab is also developing novel siRNA therapeutics to treat cancer. Using TAT Peptide Transduction Domain (PTD) fused to a dsRNA Binding Domain (PTD-DRBD), his lab has developed an efficient siRNA cellular delivery system that targets all cell types. PTD-DRBD mediated delivery of EGFR and Akt2 siRNAs induces a synthetic lethal RNAi response in intracranial glioblastoma mouse models in vivo. His lab is currently devising the next generation of siRNA delivery approaches using synthetic bioreversible phosphotriester chemistry.

SELECTED PUBLICATIONS

1. Eguchi, A., Meade, B.R., Fredrickson, C.T., Willert, K., Puri, N., and Dowdy, S.F. 2009. Efficient siRNA delivery into primary cells by peptide transduction-dsRNA binding domain (PTD-DRBD) fusion protein. Nature Biotech. 27:567-571.

2. Michiue, H., Eguchi, A., Meade, B.R., Scadeng, M., and Dowdy, S.F. 2009. Induction of in vivo synthetic lethal RNAi responses to treat glioblastoma. Cancer Biol. & Ther. 8:2306-231

3. Gump, J.M., June, R., and Dowdy, S.F. 2010. Revised Role of Glycosaminoglycans in TAT PTD-Mediated Cellular Transduction. J. Biol. Chem 285:1500-1507.

Awards and Honors Member, National Academy of Sciences Member, American Academy of Arts and Sciences Fellow, American Association for Advancement of

Science Member, Institute of Medicine

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Jeffry D. Esko, Ph.D. Professor of Cellular and Molecular Medicine Co-Director, Glycobiology Research and Training Center Phone: (858) 822-1100 E-Mail: jesko@ucsd.edu Website: http://eskolab.ucsd.edu/

!RESEARCH INTERESTS

• Chemical and genetic analysis of proteoglycan assembly • Proteoglycan function in lipoprotein metabolism and vascular biology

RESEARCH SUMMARY Research in Dr. Jeffrey Esko’s lab utilizes a combination of chemistry, biochemistry and genetics to understand the structure and function of proteoglycans containing heparan sulfate or chondroitin/dermatan sulfate glycosaminoglycans, known as proteoglycans. These molecules are ubiquitously distributed on cells and in extracellular matrices and are evolutionarily conserved from Hydra to humans. Numerous cell and organismal mutants altered in genes that encode biosynthetic enzymes and proteoglycan core proteins have been generated to analyze proteoglycan function in normal physiology and disease.

SELECTED PUBLICATIONS FROM 2010 1. Sarrazin S., Wilson B., Sly W.S., Tor Y., Esko J.D. 2010. Guanidinylated neomycin mediates heparan sulfate-dependent

transport of active enzymes to lysosomes. Mol. Therapy 18:1268-1274. PMID: 20442709 PMC2911259 2. Bishop, J.R., Passos-Bueno, M.R., Fong, L., Stanford, K.I., Gonzales, J.C., Yeh, E., Young, S.G., Bensadoun, A., Witztum,

J.L., Esko, J.D., Moulton, K.S. 2010. Deletion of the basement membrane heparan sulfate proteoglycan Type XVIII collagen causes hypertriglyceridemia in mice and humans. PLoS One. 5:e13919. PMID: 21085708!

3. Xu, D., Fuster, M.M., Lawrence, R., and Esko, J.D. 2010. Heparan sulfate regulates VEGF165 and VEGF121-mediated vascular hyperpermeability. J Biol Chem. 286:737-745. PMID: 20974861 !

Marilyn G. Farquhar, Ph.D. Distinguished Professor of Cellular and Molecular Medicine Professor of Pathology

Phone: (858) 534-7711 E-Mail: mfarquhar@ucsd.edu Website: http://cmm.ucsd.edu/Lab_Pages/farquhar/

RESEARCH INTERESTS

• Signaling and Membrane trafficking: Defining signaling networks that link G protein signaling and growth factor signaling • Cell biology of the podocyte: Defining its role in the pathogenesis of glomerular diseases

RESEARCH SUMMARY One of the main interests of the Farquhar Lab is to understand the interplay between growth factor and G protein mediated signaling networks and how this signaling is spatially regulated by trafficking. This year we have been studying the role of GIV/Girdin, a non-receptor GEF for G"i proteins, in regulating the cells response to growth factors. Cells respond to growth factors by either migrating or dividing. We discovered that GIV orchestrates this migration-proliferation dichotomy by activating G"i and forming a G"i-GIV-EGFR signaling complex thereby enhancing motogenic signals. GIV may also be involved in cancer progression because we found that in slow growing, highly motile cancer cells GIV is highly expressed and has an intact GEF motif, whereas rapidly growing, poorly motile cancer cells express a splice variant of GIV lacking its GEF motif.

SELECTED PUBLICATIONS FROM 2010 1. García-Marcos, M., Ghosh, P., Ear, J., and M.G. Farquhar. 2010. A structural determinant that renders G"(i) sensitive to

activation by GIV/girdin is required to promote cell migration. J Biol Chem. 285(17):12765-77. PMID: 20157114 2. Ghosh, P., Beas, A.O., Bornheimer, S.J., Garcia-Marcos, M., Forry, E.P., Johannson, C., Ear, J., Jung, B.H., Cabrera, B.,

Carethers, J.M., and M.G. Farquhar. 2010. A G"i-GIV molecular complex binds epidermal growth factor receptor and determines whether cells migrate or proliferate. Mol Biol Cell. 21(13):2338-54. PMCID: PMC2893996

Awards and Honors Doctor of Medicine (Honoris causa), Uppsala Universitet, Sweden

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Awards and Honors Member, National Academy of Sciences Member, American Academy of Arts and Sciences Wilson Medal, American Society of Cell Biology Homer Smith Award, American Society of Nephrology Chancellor’s Award for Excellence in Research, UCSD

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James R. Feramisco, Ph.D. Adjunct Professor of Cellular and Molecular Medicine

Professor of Medicine and Pharmacology

Phone: (858) 534-7287

E-Mail: jferamisco@ucsd.edu

Website: http://cmm.ucsd.edu/Lab_Pages/feramisco

!RESEARCH INTERESTS

• Cell growth control, cardiac disease, differentiation and light microscopic imaging

RESEARCH SUMMARY Dr. Feramisco’s research interests lie in the broad area of understanding the biochemical basis of the signal transduction pathways that regulate cell growth. His work is aimed primarily at the analysis of the function of the intracellular protooncogene products, and extends into studies of the common signals that may regulate certain types of cancer cell growth, differentiation and cardiac hypertrophy. He is also interested in use of modern light microscopic methods (quantitative image analysis, time-lapse microscopy, image deconvolution and microscopy of fixed tissue and live cells) to answer questions in cell biology. He initiated the formation of the UCSD Cancer Center Microscopy Shared Resource and has led it since 1998. He was the inaugural Director of the UCSD School of Medicine Microscopy Core, which was established to house multiple, independent shared microscopy cores.

SELECTED PUBLICATIONS 1. Gao, M.H., Tang, T., Miyanohara, A., Feramisco, J.R., and Hammond, H.K. 2010. Beta(1)-Adrenergic receptor vs

adenylyl cyclase 6 expression in cardiac myocytes: differences in transgene localization and intracellular signaling. Cell Signal. 22:584-9.

2. Gao, M.H., Miyanohara, A., Feramisco, J.R., and Tang, T. 2009. Activation of PH-domain leucine-rich protein phosphatase 2 (PHLPP2) by agonist stimulation in cardiac myocytes expressing adenylyl cyclase type 6. Biochem Biophys Res Commun. 384:193-8.

Susan Ferro-Novick, Ph.D. Professor of Cellular and Molecular Medicine Investigator, Howard Hughes Medical Institute Phone: (858) 246-0466 E-Mail: sferronovick@ucsd.edu Website: http://cmm.ucsd.edu/Lab_Pages/ferronovick/index.htm

RESEARCH INTERESTS

• Vesicle Traffic: Specificity of traffic from the endoplasmic reticulum to the Golgi • Organelle Inheritance: How organelles are inherited from Mother to Daughter cells

RESEARCH SUMMARY

The Ferro-Novick’s group focuses on how specificity of vesicle traffic is maintained and how organelles are inherited. Using a vesicle binding assay with in vitro formed ER-derived vesicles and a pure multiprotein complex named TRAPP I, they demonstrated that TRAPP I specifically binds the ER to Golgi vesicles, implying that it plays a key role in conferring specificity of ER to Golgi vesicle traffic. A genetic approach identified genes whose products are required for ER inheritance, including a motor and its track used to move ER tubules into daughter cells and a putative cortical ER receptor in those cells.

SELECTED PUBLICATIONS FROM 2010 1. Lynch-Day, M.A., Bhandari, D., Menon, S. Huang, J., Cai, H., Bartholomew, C.R., Brummell, J.H., Ferro-Novick, S.*

and Klionsky, D.J.*. 2010. Trs85 directs a Ypt1 GEF, TRAPPIII, to the phagophore to promote autophagy. PNAS 107: 7811-7816. (*co-corresponding senior authors) (rev by Faculty 1000)

2. Barrowman, J., Bhandari, D., Reinisch, K. and Ferro-Novick, S. 2010. TRAPP complexes in membrane traffic: convergence through a common Rab. Nat Rev Mol. Cell 11: 759-763.

3. Li, X., Du, Y., Siegel, S., Ferro-Novick, S.* and Novick. P.* 2010. Activation of the MAP kinase, Slt2p, at bud tips blocks a late stage of ER inheritance in Saccharomyces cerevisae. Mol. Biol. Cell 21:1772-1782. (*co-corresponding senior authors)

4. Sclafani, A., Chen, S., Rivera-Molina, F., Reinisch, K., Novick, P. and Ferro-Novick, S. 2010. Establishing a role for the GTPase Ypt1p at the late Golgi. Traffic 11:520-532.

Awards and Honors Honorary Member, American Society for Clinical Investigation

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Xiang-Dong Fu, Ph.D. Professor of Cellular and Molecular Medicine Phone: (858) 534-4937 E-Mail: xdfu@ucsd.edu Website: http://cmm.ucsd.edu/Lab_Pages/fu/research.html

RESEARCH INTERESTS • Molecular and cell biology of RNA processing • Regulation of alternative splicing by signaling • Functional genomics of RNA binding proteins • Regulated gene expression in cancer

RESEARCH SUMMARY Dr. Xiang-Dong Fu’s laboratory is interested in molecular and cell biology of RNA processing. Current focus of the lab is on genome-wide analysis of RNA binding splicing regulators to deduce rules that govern the splice site selection, the interplay between transcription and pre-mRNA splicing, and the regulation of alternative splicing in response to signaling. The Fu lab is also interested in molecular link between chromatin structure and transcriptional activation and nuclear architecture underlying regulated gene expression at both the transcriptional and post-transcriptional levels. Besides basic research fronts, the Fu lab is also developing a novel technological platform for conducting small molecular screens against androgen refractory prostate tumors.

SELECTED PUBLICATIONS 1. Fox-Walsh, K. and Fu, X-D. 2010. Chromatin: The last frontier in splicing regulation? Dev Cell 18:336-338. 2. Han, J., Ding, J-H., Byeon, C. W., Kim, J. H., Hertel, Jeong, S., and Fu, X-D. 2011. SR proteins induce alternative exon

skipping through their activities on the flanking constitutive exons. Mol Cell Biol. 31:793-802. 3. Hairsmendy, O., Notani, D., Rahim, N. Song, X. Y., Tanasa, B., Heintzman, N., Ren, B., Fu X-D., Topol, E., Rosenfeld,

MG., and Frazer, K. 2010. 9p21 DNA variants associated with coronary artery disease impair IFNg signaling response. Nature. In press.

4. Wang, W., Barnaby, J., Tada, Y., Li, H., Tor, M., Caldelari, D., Lee, D. U., Fu X-D., and Dong, X. 2010. Timing of plant immune responses by a central circadian regulator. Nature. In press.

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Pascal Gagneux, Ph.D. Assistant Adjunct Professor of Cellular and Molecular Medicine Phone: (858) 822-4030 E-Mail: pgagneux@ucsd.edu Website: http://cmm.ucsd.edu/Lab_Pages/Gagneux/

RESEARCH INTERESTS

• Evolution of molecular diversity, host-pathogen co-evolution, reproduction, glycobiology

RESEARCH SUMMARY Glycosylation, the post-translational modification of proteins and lipids with oligosaccharide chains (glycans), plays many roles throughout life history. These include cellular recognition phenomena during fertilization, development, infection, immune regulation, and cancer. There is much variation in glycans between species, between individuals of the same species, and even between different cell types of the same organism. Mammalian reproduction requires internal fertilization, necessitating the survival of foreign cells (sperm) within the female until fertilization. This process shares many aspects with successful infection. Understanding how sperm cells interact with the female via their surface glycans, prompting female tolerance and allowing fertilization, promises new understanding of cellular recognition mechanisms and insights into the molecular basis of reproductive incompatibility.

SELECTED PUBLICATIONS 1. Adibekian, A, P Stallforth, Hecht, M., Werz, D.B., Gagneux, P., and Seeberger, P.H. 2010. Comparative bioinformatics

analysis of the mammalian and bacterial glycomes. Chemical Science. Advanced publication. 2. Tao, N., Wu, S., Kim, J., An, H.J., Hinde, K., Power, M., Gagneux, P., German, J.B., Lebrilla, C.B.J 2011. Evolutionary

Glycomics: Characterization of Milk Oligosaccharides in Primates. Proteome Res. Jan 11, 2011. Epub ahead of print. 3. Dall'olio, G.M., Jassal, B., Montanucci, L., Gagneux, P., Bertranpetit, J,. Laayouni, H. 2011. The annotation of the

Asparagine N-linked Glycosylation pathway in the Reactome Database. Glycobiology. Jan 2, 2011. Epub ahead of print.

Awards and Honors Fellow, American Association for Advancement of

Science, 2010

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Gordon N. Gill, M.D. Professor Emeritus of Medicine and Cellular and

Molecular Medicine Dean, Scientific Affairs

Phone: (858) 534-4310 E-Mail: ggill@ucsd.edu Website: http://cmm.ucsd.edu/Lab_Pages/gill/index.htm

RESEARCH SUMMARY Dr. Gordon Gill’s research interest is in neural development. The LIM-homeodomain (LIM-HD) “code” that specifies development of neuronal subtypes depends on the nuclear LIM interactor adaptor protein NLI. The molecular function of nuclear LIM domain only proteins (LMO) has been unclear. The group has shown that the major neuronal expressed LMO, LMO4, acts as a feedback inhibitor of the LIM-HD protein isl-1-directed development of motor neurons while acting as a positive cofactor with NLI for development of inhibitory V2b interneurons. Functions of specific molecules thus depends on the context in which they are expressed and the stiochiometries of each protein component as shown previously for the LIM-HD proteins isl-1 and Lhx3 in motor neuron development.

The “small” RNA polymerase II C-terminal domain phosphatase Scp1 exhibits specificity for P-Ser5 in the heptad repeats and has been implicated in neural stem cell maintenance. The Gill group has now extended structural studies of Scp1 to capture “snapshots,” i.e., co-crystal structures of the phosphoryl transfer reaction at each step of Scp1- mediated catalysis. They have initiated a screen for small molecular inhibitors of Scp1 to use in studies of neural stem cell development and as drug candidates to induce neural stem cell development to repair damage, and have several “hits” that fit well.

SELECTED PUBLICATIONS FROM 2010 1. Zhang, M., Liu, J., Kim, Y-J., Dixon, J.E., Gill, G.N., Noel, J. and Zhang, Y. 2010. Structural and Functional Analysis of

the Phosphoryl Transfer Reaction Mediated by the Human Small C-Terminal Domain Phosphatase, Scp1. Protein Science 19:974-986.

2. Zhang, M, Gill, G.N. and Zhang Y. 2010. Bio-Molecular architects: a scaffold provided by the C-terminal domain of eukaryotic RNA polymerase II. Nano Reviews 1:5502-DoI: 10.3402/nano.v1i0.5502, 1-11.

Christopher K. Glass, M.D., Ph.D. Professor of Cellular and Molecular Medicine Professor of Medicine Phone: (858) 534-6011 E-Mail: cglass@ucsd.edu Website: http://cmm.ucsd.edu/Lab_Pages/glass/glasslab/

RESEARCH INTERESTS

• Regulation of macrophage gene expression

RESEARCH SUMMARY Dr. Christopher Glass’ laboratory investigates the mechanisms by which sequence-specific transcription factors regulate the development and function of macrophages. A combination of biochemical, cellular and in vivo model systems are used, incorporating macrophage-specific knockouts, high throughput technologies and bioinformatics approaches, to unravel the contributions of specific transcription factors in the development of specialized macrophage functions and the pathogenesis of inflammatory diseases.

SELECTED PUBLICATIONS FROM 2010 1. Harmon, G.S., Dumlao, D.S., Ng, D.T., Barrett, K.E., Dennis, E.A., Dong, H., and Glass, C.K. 2010. Pharmacological

correction of a defect in PPAR-gamma signaling ameliorates disease severity in Cftr-deficient mice. Nat. Med. 16:313-318. 2. Heinz S, Benner C, Spann NJ, Bertolino E, Lin YC, Laslo P, Cheng JX, Murre C, Singh H, Glass CK. 2010. Simple

combinations of lineage-determining transcription factors prime cis-regulatory elements required for macrophage and B cell identities. Mol. Cell 38:576-89. PMID: 20543837

3. Huang, W., Ghisletti, S., Saijo, K., Gandhi, M., Aouadi, M., Zhang, D., Yao, J., Czech, M., Goode, B.L., Rosenfeld, M.G., and Glass, C.K. 2010. Coronin2A mediates actin-dependent de-repression of inflammatory response genes. Nature. In press.

Awards and Honors Member, American Academy of Arts and Sciences Member, American Society for Clinical Investigation

Awards and Honors Member, Association of American Physicians Member, American Society for Clinical Investigation

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Lawrence S. B. Goldstein, Ph.D. Distinguished Professor of Cellular and Molecular Medicine Investigator, Howard Hughes Medical Institute

Phone: (858) 534-9702 E-Mail: lgoldstein@ucsd.edu Website: http://cmm.ucsd.edu/Lab_Pages/goldstein/index.html

RESEARCH INTERESTS • Molecular mechanisms of intracellular movement in neurons: role of transport dysfunction in neurodegenerative disease • Focus on microtubule motor proteins • Stem cell biology • Alzheimer’s Disease and Lou Gehrig's Disease (ALS)

RESEARCH SUMMARY

The Goldstein Laboratory is interested in understanding the molecular mechanisms of intracellular movement and the role of transport dysfunction in neurodegenerative diseases. They foucs on the attachment, function, and regulation of the microtubule motor proteins kinesin and cytoplasmic dynein. They also use human neurons to probe the role of genes in basic cell biology and disease development.

SELECTED PUBLICATIONS

1. Goldstein L.S.B., Schneider M. 2010. Stem Cells For Dummies. Wiley Publishing. 2. Goldstein L.S.B. 2010. Unconventional allies: interdisciplinary approaches to science policy and funding. Trends Cell Biol.

20:695-8. 3. Falzone, T.L., Gunawardena, S., McCleary, D., Reis, G.F, and Goldstein, L.S. 2010. Kinesin-1 transport reductions

enhance human tau hyperphosphorylation, aggregation and neurodegeneration in animal models of tauopathies. Hum Mol Genet. 19:4399-408.

4. Falzone, T.L., Stokin, G.B., Lillo, C., Rodrigues, E.M., Westerman, E.L., Williams, D.S., and Goldstein, L.S. 2009. Axonal stress inase ctivation and tau misbehavior induced by kinesin-1 transport defects. J Neurosci. 29:5758-67.

Bruce A. Hamilton, Ph.D. Associate Adjunct Professor of Cellular and Molecular Medicine Associate Professor of Medicine Phone: (858) 822-1055 E-Mail: bahamilton@ucsd.edu Website: http://cmm.ucsd.edu/Lab_Pages/hamilton/bah/index.html

RESEARCH INTERESTS

! • Human genetics, mouse models, neural stem cells, brain development, hypertension

RESEARCH SUMMARY

Dr. Bruce Hamilton and his laboratory are interested in genetic architectures and genomic responses in brain development, neurological disorders, and neural control of blood pressure regulation. Recent work has focused on modifier genes and gene networks in mouse models, with particular emphasis on therapeutic range in genetic titration experiments, and on functional variation in hypertension candidate genes in humans.

SELECTED PUBLICATIONS

1. Concepcion, D., Flores-García, L., and Hamilton, B.A. 2009. Multipotent genetic suppression of retrotransposon-induced mutations by Nxf1 through fine-tuning of alternative splicing. PLoS Genetics 5. e1000484.

2. Hamilton, B.A., and Wynshaw-Boris, A. 2009. “Basic Genetics and Patterns of Inheritance” in Maternal-Fetal Medicine, Creasy, R.K., Resnik, R., and Iams, eds. Sixth edition. Saunders, Philadelphia, PA.

3. Chen, Y., Wen, G., Rao, F., Zhang, K., Wang, L., Rodriguez-Flores, J.L., Sanchez, A.P., Mahata, M., Taupenot, L., Sun, P., Mahata, S.K., Tayo, B., Schork, N.J., Ziegler, M.G., Hamilton, B.A., O'Connor, D.T. 2010. Human dopamine beta-hydroxylase (DBH) regulatory polymorphism that influences enzymatic activity, autonomic function, and blood pressure. J Hypertens. 28(1):76-86.

Awards and Honors Member, American Academy of Arts and Sciences 2009 American Society for Cell Biology Public Policy Award

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Stephen M. Hedrick, Ph.D. Distinguished Professor of Cellular and Molecular Medicine Professor and Chair of Molecular Biology, Division of Biology Chancellor’s Endowed Chair in the Biological Sciences Phone: (858) 534-6559 E-Mail: shedrick@ucsd.edu Website: http://hedricklab.ucsd.edu/

RESEARCH INTERESTS

• Homeostasis within the immune system: T cell survival, proliferation, and differentiation • The co-evolution of parasitic virulence factors and host immunity

RESEARCH SUMMARY

The Hedrick group studies the basic processes of T lymphocyte development and activation. They are interested in the concepts underlying lineage decisions that govern the maturation of different T cell subsets as well as memory T cells. In particular, they are studying two signaling modules, anchored by Foxo, Erk, and Caspase-8, that integrate a great deal of information in order to guide progression through the cell cycle, survival, or various forms of programmed cell death. The information is important in understanding the balance between protective- vs. auto-immunity.

SELECTED PUBLICATIONS 1. Hedrick, S. M., I. L. Ch’en, and B. N. Alves. 2010. Intertwined pathways of programmed cell death in immunity. Immunol

Rev. 236:41-53. 2. Kerdiles, Y. M., E. L. Stone, D. L. Beisner, M. A. McGargill, I. L. Ch’en, C. Stockmann, C. D. Katayama, and S. M.

Hedrick. 2010. Foxo transcription factors control regulatory T cell development and function. Immunity. 33:890-904. 3. Dejean, A. S., S. M. Hedrick, and Y. M. Kerdiles. 2010. Highly specialized role of Foxo transcription factors in the

immune system. Antioxid Redox Signal 14:Dec 13, ePub ahead of print. 4. McGargill, M. A., I. L. Ch’en, C. D. Katayama, G. Pages, J. Pouyssegur, and S. M. Hedrick. 2009. Cutting edge:

Extracellular signal-related kinase is not required for negative selection of developing T cells. J Immunol. 183:4838-4842. 5. Hedrick, S. M. 2009. Immune system: not so superior. Science 325:1623-1624.

Yishi Jin, Ph.D. Professor of Cellular and Molecular Medicine Professor of Biological Sciences Investigator, Howard Hughes Medical Institute Phone: (858) 534-7754 E-Mail: yijin@ucsd.edu Website: http://www.biology.ucsd.edu/labs/yishijin/

RESEARCH INTERESTS • Molecular genetics of synapse formation • Molecular genetics of axon regeneration

RESEARCH SUMMARY

Dr. Yishi Jin’s laboratory studies neurodevelopment using nematode C. elegans. The complexity of synaptic connections in a nervous system is astronomic. The molecular mechanisms underlying how synapses are formed remain poorly understood. By examining genetic mutants that exhibit defects in synapses, they have discovered multiple signaling pathways that play conserved roles in synapse formation. This year, their studies uncovered an intriguing role of nuclear polyadenylation in synapse development. Their recent interests have also expanded into dissection of genetic factors that influence adult neuron regenerative ability in responses to injury. Their studies have revealed a critical role of a conserved MAPKKK in injury response and demonstrate a mechanism of local translation in synapse maintenance and axon regeneration.

SELECTED PUBLICATIONS 1. Van Epps, H., Dai, Y., Qi, Y. B., Goncharov, A., and Jin, Y. 2010. Nuclear pre-mRNA 3’ end cleavage and

polyadenylation regulate synapse and axon development in C. elegans. Development. 137: 2237-2250. 2. Yan, D., Wu, Z., Chisholm, A.D., and Jin, Y. 2009. The DLK-1 kinase promotes mRNA stability and local translation in

synapses and axon regeneration. Cell 138:1005-18. 3. Jospin, M., Stawicki, T., Qi, Y., Boulin, T., Horvitz, H. R., Bessereau, J. L., Jorgensen, E., and Jin, Y. 2009. An neuronal

acetylcholine receptor regulates C. elegans locomotion. PLoS Biol. 7:e1000265.

Awards and Honors Fellow, American Association for Advancement of

Science, 2010

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Richard Kolodner, Ph.D. Distinguished Professor of Cellular and Molecular

Medicine Professor of Medicine Investigator, Ludwig Institute for Cancer Research Phone: (858) 534-7804 E-Mail: rkolodner@ucsd.edu Website: http://sandiego.licr.org/D_groups/

d3_Cancer-Genetics

RESEARCH INTERESTS

• Cancer Genetics

RESEARCH SUMMARY

The Kolodner laboratory is studying the genetic and biochemical mechanisms of genetic recombination, DNA repair and suppression of mutations primarily using Saccharomyces cerevisiae as a model system. A central interest is to elucidate the mechanisms of the DNA mismatch repair (MMR) pathways that prevent cells from accumulating mutations due to errors in DNA replication. A second interest is to define the pathways that prevent the accumulation of genome rearrangements like translocations seen in many types of cancer cells. A final interest is in understanding whether genes that prevent genome instability are tumor suppressor genes and if defects in these genes can be exploited for therapeutic means.

SELECTED PUBLICATIONS 1. Putnam, CD, Hayes, TK, and Kolodner, RD. 2009. Specific pathways prevent duplication-mediated genome

rearrangements. Nature. 460:984-989. 2. Martinez, S, and Kolodner, RD. 2010. Functional analysis of human mismatch repair gene mutations identifies weak

alleles and polymorphisms capable of polygenic interactions. Proc. Natl. Acad. Sci. USA. 107:5070-5075. 3. Bandyopadhyay, S, Mehta, M, Kuo, D, Sung, M-K, Chuang, R, Jaehnig, E, Bodenmiller, B, Licon, K, Copeland, W, Shales,

M, Fiedler, D, Dutkowski, J, Guenole, A, van Attikum, H, Shokat, KM, Kolodner, RD, Huh, W-K, Aebersold, R, Keogh, M-C, Krogan, NJ, and Ideker, T. 2010. Rewiring of genetic networks in response to DNA damage. Science. 330:1385-1389.

Albert La Spada, M.D., Ph.D. Professor of Cellular and Molecular Medicine Associate Director, Institute for Genomic Medicine Professor & Division Head of Genetics, Dept. of Pediatrics Professor of Biological Sciences Phone: (858) 246-0148 E-Mail: alaspada@ucsd.edu Website: http://biomedsci.ucsd.edu/faculty_descrip.asp?id=277

RESEARCH INTERESTS • Genetics and mechanisms of neurologic disease, and design of strategies for therapy

RESEARCH SUMMARY Dr. La Spada’s group is interested in the molecular basis of neurodegenerative disease, and studies human genetic diseases caused by expansions of CAG-polyglutamine repeats, including Huntington’s disease, spinobulbar muscular atrophy, and spinocerebellar ataxia type 7. Dr. La Spada’s team has uncovered evidence for transcription dysregulation in these disorders, and is studying the role of small RNAs in neurons to identify epigenetic changes associated with neurodegeneration and aging. The La Spada lab is defining the genetic regulation of protein quality control in the CNS, as neurons are exquisitely susceptible to misfolded protein stress and thus must rely upon autophagy for proteostasis. His group is also focused upon bioenergetics and mitochondrial quality, as energy status is a key factor in neuron survival and neurodegenerative disease. Their ultimate goal is to define pathways by which neurons become dysfunctional and use this knowledge to devise rational therapies. SELECTED PUBLICATIONS FROM 2010 1. La Spada, A.R. and Taylor J.P. 2010. Repeat expansion disease: Progress and puzzles in disease pathogenesis. Nature

Rev. Genet. 11: 247-258. 2. Chakrabarti L., Zahra R., Jackson S.M., Kazemi-Esfarjani P., Sopher B.L., Mason A.G., Toneff T., Ryu S., Shaffer S.,

Kansy J.W., Eng J., Merrihew G., MacCoss M.J., Murphy A., Goodlett D.R., Hook V., Bennett C.L., Pallanck L.J. and La Spada AR. 2010. Mitochondrial dysfunction in NnaD mutant flies and Purkinje cell degeneration (pcd) mice reveals a role for Nna proteins in neuronal bioenergetics. Neuron. 66: 835-845.

Awards and Honors Member, American Society for Clinical Investigation Paul Beeson Physician Faculty Scholar Lieberman Award from the Hereditary Disease

Foundation

Awards and Honors Member, National Academy of Sciences Member, American Academy of Arts and Sciences The Charles S. Mott Prize from the General Motors

Cancer Research Foundation The Kirk A. Landon-AACR Prize for Basic Cancer

Research

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Jonathan H. Lin, M.D., Ph.D. Assistant Adjunct Professor of Cellular and Molecular Medicine Assistant Professor of Pathology

Phone: (858) 534-2743 E-Mail: jlin@ucsd.edu Website: http://www.linlab.ucsd.edu/

RESEARCH INTERESTS

• Endoplasmic Reticulum Stress and Protein Folding in Development and Disease • Neurodegeneration/Retinal Degeneration

RESEARCH SUMMARY

The Lin lab studies cellular and molecular mechanisms by which cells detect and cope with misfolded proteins and endoplasmic reticulum stress. The Lin lab also examines whether artificial manipulation of these mechanisms can prevent the development of human diseases arising from protein misfolding and ER stress. Recently, the lab has focused on studying the role of ER stress in heritable forms of retinal degeneration.

SELECTED PUBLICATIONS

1. Lisbona, F., Rojas-Rivera, D., Thielen, P., Zamorano, S., Todd, D., Martinon, F., Glavic, A., Kress, C., Lin, J.H., Walter, P., Reed, J.C., Glimcher, L.H., and Hetz, C. 2009. BAX Inhibitor-1 is a negative regulator of the ER stress sensor IRE1a. Molecular Cell. 33:679-691.

2. Lin, J.H., Li, H., Zhang, Y., Ron, D., and Walter, P. 2009. Divergent effects of PERK and IRE1 signaling on cell viability. PLoS ONE. 4:e4170.

3. Hollien, J., Lin, J.H., Li, H., Stevens, N., Walter, P., and Weissman, J.S. 2009. Regulated Ire1-dependent decay of mRNAs in mammalian cells. J Cell Biol. 186:326-331.

Alysson R. Muotri, Ph.D. Assistant Professor of Cellular and Molecular Medicine Assistant Professor of Pediatrics Phone: (858) 534-9320 E-Mail: muotri@ucsd.edu Website: http://biomedsci.ucsd.edu/faculty_descrip.asp?id=260

RESEARCH INTERESTS

• Molecular and cellular mechanisms of neurological disorders • Activity and consequences of mobile elements in the nervous system

RESEARCH SUMMARY

The Muotri laboratory explores mobile elements as generators of diversity during neuronal differentiation. These mobile elements may be part of a conserved genetic core process responsible for evoking facilitated complex non-random phenotypical variation in which selection may act. They use animal models, neural stem cells, human and other primates’ pluripotent cells and several molecular tools to investigate fundamental mechanisms of brain development, evolution and mental disorders, such as Autism Spectrum Disorders.

SELECTED PUBLICATIONS FROM 2010

1. Marchetto, M. C. N., Carromeu, C., Acab, A., Yu, D., Yeo, G., Yangling, M., Gage, F. H. and Muotri, A. R. 2010. A model for neural development and treatment of Rett syndrome using human induced pluripotent stem cells. Cell. 143(4): 527-39.

2. Muotri, A. R., Marchetto, M. C. N., Coufal, N. G., Oefner, R., Yeo, G., Nakashima, K. & Gage, F. H. 2010. L1 retrotransposition in neurons is modulated by MeCp2. Nature. 468(7322): 443-6.

Awards and Honors

CIRM Early Translational II Award, 2010

Awards and Honors

American Society for Investigative Pathology Excellence in Science Young Faculty Award, 2009 Karl Kirchgessner Foundation New Faculty Award, 2010 Hope for Vision Foundation New Faculty Award, 2010

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Sanjay Nigam, M.D. Professor of Cellular and Molecular Medicine Professor of Pediatrics Phone: (858) 822-3482 E-Mail: snigam@ucsd.edu

RESEARCH SUMMARY

Dr. Sanjay Nigam’s research focuses on the molecular and cellular mechanisms of branching morphogenesis as they relate to organ development (e.g. kidney, lung). They are also investigating the use of developmental approaches to “tissue engineer” epithelial organs. Another major area is researching the molecular mechanisms of drug elimination by the kidney and the role of polymorphisms in determining human drug response.

SELECTED PUBLICATIONS FROM 2010

1. Shah, M.M., Sakurai, H., Sweeney, D.E., Gallegos, T.F., Bush, K.T., Esko, J.D, Nigam, S.K. 2010. Hs2st mediated kidney mesenchyme induction regulates early ureteric bud branching. Dev Biol. 339(2):354-65.

2. Rosines, E., Johkura, K., Xing Zhang, X., Schmidt, H.J., DeCambre, M., Bush, K.T., Nigam, SK. 2010. Constructing kidney-like tissues from cells based on programs for organ development: towards a method of in vitro engineering of the kidney. Tissue Eng Part A. 16(8):2441-55.

3. Nagle, M.A., Truong, D.M., Dnyanmote, A.V., Ahn, S.Y., Eraly, S.A., Wu, W., Nigam, S.K. 2010. Analysis of three-dimensional systems for developing and mature kidneys clarifies the role of OAT1 and OAT3 in antiviral handling. J Biol Chem. 286(1):243-51.

4. Tee, J.B., Choi, Y., Shah, M.M., Dnyanmote, A., Sweeney, D.E., Gallegos, T.F., Johkura, K., Ito, C., Bush, K.T., Nigam, S.K. 2010. Protein kinase A regulates GDNF/RET-dependent but not GDNF/Ret-independent ureteric bud outgrowth from the Wolffian duct. Dev Biol. 347(2):337-47.

Peter Novick, Ph.D. Professor of Cellular and Molecular Medicine The George Palade Endowed Chair Phone: (858) 246-0465 E-Mail: pnovick@ucsd.edu

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RESEARCH INTERESTS

• Molecular mechanisms of polarized vesicular transport, role of small GTPases (Rabs) in regulation of membrane traffic, structure and inheritance of the endoplasmic reticulum

RESEARCH SUMMARY

The Novick group focuses on the regulation of membrane traffic by Rab GTPases. Rabs recruit effectors that control specific aspects of membrane traffic such as the transport of vesicles along cytoskeletal elements, the recognition of the vesicle by the target membrane and the fusion of the vesicle and target membranes. Regulatory networks coordinate one stage of traffic with adjacent stages. Once a Rab is activated it recruits a guanine nucleotide exchange factor (GEF) that activates the downstream Rab as well as a GTPase activating protein (GAP) that inactivates the upstream Rab. The net effect is a programmed series of Rab conversions. With each Rab conversion a new set of effectors is recruited, leading to functional maturation of the membrane as it flows down the pathway. Another area of research addresses the unique structure of the endoplasmic reticulum and the mechanism of its inheritance during cell division.

SELECTED PUBLICATIONS FROM 2010

1. Mizuno-Yamasaki, E., Medkova, M., Coleman, J. and Novick, P. 2010. Phosphatidylinositol 4-phosphate controls both membrane recruitment and a regulatory switch of the Rab GEF Sec2p. Dev Cell. 18:828-40.

2. Li X., Du, Y., Siegel, S., Ferro-Novick. S. and Novick, P. 2010. Activation of the MAP kinase, Slt2p, at bud tips blocks a late stage of ER inheritance in Saccharomyces cerevisiae. Mol Biol Cell. 21:1772-82.

Awards and Honors Member, American Academy of Arts and Sciences Member, American Academy of Microbiology Inaugural Recipient of the George Palade Endowed

Chair Member, American Association for Advancement of

Science, 2010

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Karen Oegema, Ph.D.! Professor of Cellular and Molecular Medicine Member, Ludwig Institute for Cancer Research Phone: (858) 534-9714 E-Mail: koegema@ucsd.edu

RESEARCH INTERESTS

• Molecular mechanics of cytokinesis • Centrosome duplication and maturation • Functional genomics of cell division

RESEARCH SUMMARY The Oegema group has focused on developing C. elegans as a model system for mechanistic cell biology. The laboratory has used the C. elegans system to address fundamental questions in two main areas: (1) cytokinesis, and (2) centriole duplication and function. In cytokinesis, the group has focused on understanding how the contractile ring forms in response to signals from the anaphase spindle and how it constricts to partition the cell contents. In the area of centrosome function, the group has focused on understanding how centrioles duplicate and recruit pericentriolar material to form centrosomes, the major microtubule organizing centers in animal cells.

SELECTED PUBLICATIONS

1. Lewellyn, L., Dumont, J., Desai, A. and Oegema, K. Analyzing the effects of delaying aster separation on furrow formation during cytokinesis in the C. elegans embryo. 2010. Mol. Biol. Cell. 21:50-62.

2. Dammermann, A., Pemble, H., Mitchell B. J., McLeod, I., Yates III, J.R., Kintner, C., Desai, A.B., and Oegema, K. 2009. The Hydrolethalus Syndrome protein HYLS-1 links core centriole structure to cilia formation. Genes Dev. 23:2046-59.

3. Carvalho, A., Desai, A., and Oegema, K. 2009. Structural memory in the contractile ring makes the duration of cytokinesis independent of cell size. Cell. 137:926-937.

Bing Ren, Ph.D.

Professor of Cellular and Molecular Medicine Member, Ludwig Institute for Cancer Research Phone: (858) 822-5766 E-Mail: biren@ucsd.edu Website: http://licr-renlab.ucsd.edu/

RESEARCH INTERESTS

• Systematic identification and characterization of functional elements in mammalian genomes • Comprehensive analysis of epigenomes in human cells • Mechanisms of transcriptional activation from long-range acting enhancers • Mechanisms of pluripotency and cell fate determination of human embryonic stem cells

RESEARCH SUMMARY The laboratory headed by Dr. Bing Ren is focused on gene regulatory mechanisms that determine cell fate and differentiation. In particular, what are the transcriptional regulatory sequences that control cell-specific gene expression programs and what are the epigenetic processes that regulate the cell fate in each human cell type? In 2010, the laboratory generated comprehensive reference epigenome maps of human embryonic stem cells and several differentiated cell types, which revealed dramatic dramatic differences of chromatin landscapes between the pluripotent and lineage-committed cell types, suggesting potential mechanisms for differentiation and reprogramming.

SELECTED PUBLICATIONS FROM 2010 1. Hawkins, R.D., Hon, G.C., Lee, L.K., Ngo, Q., Lister, R., Pelizzola, M., Edsall, L.E., Kuan, S., Luu, Y., Klugman, S.,

Antosiewicz-Bourget, J., Ye, Z., Espinoza, C., Agarwahl, S., Shen, L., Ruotti, V., Wang, W., Stewart, R., Thomson, J.A., Ecker, J.R., Ren, B. 2010. Distinct epigenomic landscapes of pluripotent and lineage-committed human cells. Cell Stem Cell. 6(5):479-91.

2. Hawkins, R.D., Hon, G.C., Ren, B. 2010. Next-generation genomics: an integrative approach. Nature Review Genetics. 11: 476-486

Awards and Honors Pew Scholar American Society for Cell Biology Outstanding Woman Junior Award

Awards and Honors Award in NIH Epigenomics Program Young Investigator Award, The Chinese Biological

Investigator’s Society

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Maike Sander, M.D. Associate Adjunct Professor of Cellular and Molecular Medicine Associate Professor of Pediatrics

Phone: (858) 246-0843 E-Mail: masander@ucsd.edu Website: http://cmm.ucsd.edu/sander/sander/Home.html

RESEARCH INTERESTS

• Organ Stem Cells • Cell Differentiation and Regeneration

RESEARCH SUMMARY

The Sander lab focuses on understanding the molecular mechanisms that underlie the formation of endocrine cells in the pancreas. Our studies aim to identify strategies, by which to generate replacement insulin-producing cells for treatment of diabetes. Specifically, our research combines mouse genetic, ES-cell-based, biochemical and genomic approaches to identify key transcription factor-mediated gene activation and gene silencing events that control endocrine cell differentiation.

SELECTED PUBLICATIONS 1. Prakash, N., Puelles, E., Freude, K.K., Trümbach, D., Omodei, D., DiSalvio, M., Sussel, L., Ericson, J., Sander, M.,

Simeone, A., and Wurst, W. 2009. Nkx6.1 controls the identity and fate of red nucleus and oculomotor neurons in the mouse hindbrain. Development. 136:2545-2555.

2. Schaffer, A.E., Freude, K.K., Nelson, S.H., Sander, M. 2010. Ptf1a and Nkx6 transcription factors function as antagonistic lineage determinants in multipotent pancreatic progenitors. Developmental Cell. 18:1022-1029.

Jonathan Sebat, Ph.D. Assistant Professor of Cellular and Molecular Medicine Assistant Professor of Psychiatry Chief, Beyster Center for Molecular Genomics of Neuropsychiatric Diseases Phone: (858) 822-1023 E-Mail: jsebat@ucsd.edu Website: http://psychiatry.ucsd.edu/faculty/jsebat.html

RESEARCH SUMMARY The Sebat laboratory is interested in understanding the molecular basis of neuropsychiatric disorders including schizophrenia, bipolar disorder and autism. We are interested the role of copy number variants (CNVs) in disease. Our approach is to apply advanced mutation-detection methods, including microarray and Next Generation Sequencing (NGS) technologies, to identify mutations that confer high risk of disease. Further, we are investigating the functional impact of CNVs on genes and corresponding cellular pathways.

SELECTED PUBLICATIONS

1. Yoon, S., Xuan, Z., Makarov, V., Ye, K., and Sebat, J. 2009. Sensitive and accurate detection of copy number variants using read depth of coverage. Genome Res. 19:1586-92.

2. McCarthy, S.E., Makarov, V., Kirov, G., Addington, A.M., McClellan, J., Yoon, S., Perkins, D.O., Dickel, D.E., Kusenda, M., Krastoshevsky, O., Krause, V., Kumar, R.A., Grozeva, D., Malhotra, D., Walsh, T., Zackai, E.H., Kaplan, P., Ganesh, J., Krantz, I.D., …, Rapoport, J., Levy, D.L., King, M.C., and Sebat, J. 2009. Microduplications of 16p11.2 are associated with Schizophrenia. Nat Genet. 41:1223-7.

3. Girirajan, S. et al. 2010. A recurrent 16p12.1 microdeletion supports a two-hit model for severe developmental delay. Nat Genet. 42:203-9.

Awards and Honors The James M. and Cathleen D. Stone Faculty Award,

2008 Reich Young Investigator Award, International Society of

Psychiatric Genetics Investigator Award, The Chinese Biological Young

Investigator’s Society

Awards and Honors Multicenter grant from the NIH-NIDDK-Beta Cell

Biology Consortium for the development of a stem cell-based therapy for diabetes, 2010

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George L. Sen, Ph.D. Assistant Professor of Cellular and Molecular Medicine Assistant Professor of Medicine and Division of Dermatology Phone: (858) 8226-0268 E-Mail: gsen@ucsd.edu

RESEARCH INTERESTS

•Epigenetic mechanisms of epidermal stem cell self-renewal and differentiation •Transcription factor regulation of epidermal differentiation and proliferation •Gene regulatory mechanisms in tumorigenesis

RESEARCH SUMMARY Dr. George Sen’s research is focused on understanding the molecular mechanisms of epidermal stem cell self-renewal and differentiation. Perturbations in this intricate balance between growth and differentiation can lead to a variety of human skin disorders. Dr. Sen has focused on identifying epigenetic factors that have functional roles in promoting epidermal stem cell self-renewal and differentiation. His group has recently demonstrated that both regulators of H3K27me3 and DNA methylation play vital roles in epidermal stem cell self-renewal and differentiation. They demonstrated that epigenetic factors such as EZH2 and SUZ12, which mediate H3K27 trimethylation and DNA methylation enzymes such as DNMT1 are necessary for promoting adult stem cell self-renewal. Loss of these factors led to spontaneous differentiation of the interfollicular epidermis. Dr. Sen’s research in the future will continue to focus on identifying and characterizing novel regulators of epidermal homeostasis. Their ultimate goal is to define all the regulators that are important for stem cell self-renewal, differentiation, and tumorigenesis.

SELECTED PUBLICATIONS FROM 2010 1. Khavari, D.A., Sen G.L., and Rinn J.L. 2010. DNA methylation and epigenetic control of cellular differentiation. Cell Cycle 19: 3880-3. 2. Sen, G. L., Reuter, J.A., Zhu, L., and Khavari, P.A. 2010. DNMT1 maintains progenitor function in self-renewing somatic tissue. Nature 463:563-567.

Deborah Spector, Ph.D. Distinguished Professor of Cellular and Molecular Medicine Professor, Skaggs School of Pharmacy and Pharmaceutical Studies Phone: (858) 822-4003 E-Mail: dspector@ucsd.edu Website: http://cmm.ucsd.edu/Lab_Pages/Spector/

RESEARCH INTERETS • Regulation of human cytomegalovirus (HCMV) early gene expression and viral-mediated effects on cell cycle • Development of a vaccine for HCMV and Herpes Simplex Virus Type 2

RESEARCH SUMMARY

Dr. Deborah Spector’s lab focuses viral pathogenesis and the molecular mechanisms used by HCMV, the major viral cause of birth defects and a risk factor in atherosclerosis. A key discovery was that HCMV modulates the ubiquitin-proteasome pathway by inactivating the anaphase-promoting complex, the major E3 ubiquitin ligase in cell cycle regulation. They have also developed a novel strategy for developing vaccines against persistent viruses are currently testing this approach for vaccines that will protect against HCMV and Herpes Simplex Virus Type 2.

SELECTED PUBLICATIONS 1. Tran, K., Mahr, J.A., and Spector, D.H. 2009. Proteasome subunits relocalize during human cytomegalovirus infection,

and proteasome activity is necessary for efficient viral gene transcription. J Virol. 84:3079-93. 2. Sanders, R.L., and Spector, D.H. 2010. Human cytomegalovirus IE2 86 and IE2 40 proteins differentially regulate UL84

protein expression posttranscriptionally in the absence of other viral gene products. J Virol. 84:5158-70. 3. Tran, K., Kamil, J.P., Coen, D.M., and Spector, D.H. 2010. Inactivation and disassembly of the anaphase-promoting

complex during human cytomegalovirus infection is associated with degradation of the APC5 and APC4 subunits and does not require UL97-mediated phosphorylation of Cdh1. J Virol. 84:10832-43.

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Shankar Subramaniam, Ph.D. Professor of Bioengineering, Chemistry and Biochemistry, & Cellular and Molecular Medicine Chair, Department of Bioengineering Joan and Irwin Jacobs Endowed Chair in Bioengineering and Systems Biology Phone: (858) 822-0986 Fax: (858) 822-3752 Email: shankar@ucsd.edu

Website: http://genome.ucsd.edu/

RESEARCH INTERESTS

• Bioinformatics, Systems Biology and Systems Medicine

RESEARCH SUMMARY

The Subramaniam group focuses on strategies for identifying protein interaction networks, intracellular localization of proteins and identification of functional networks in cells. Included here is exploiting bioinformatics to decipher mammalian cellular networks from high throughput and phenotypic data and in developing strategies for modeling cellular signaling networks.

SELECTED PUBLICATIONS

1. Sears, D.D., Hsiao, G., Hsiao, A., Yu, J.G., Courtney, C.H., Ofrecio, J.M., Chapman, J., and Subramaniam, S. 2009. Mechanisms of human insulin resistance and thiazolidinedione-mediated insulin sensitization. Proc. Natl. Acad. Sci. U S A. 106:18745-50.

2. Gupta, S., Maurya, M.R., Stephens, D.L., Dennis, E.A., and Subramaniam, S. 2009. An integrated model of eicosanoid metabolism and signaling based on lipidomics flux analysis. Biophys. J. 96:4542-51.

David Traver, Ph.D. Associate Professor of Cellular and Molecular Medicine Associate Professor, Section of Cell and Developmental Biology Phone: (858) 822-4593 E-Mail: dtraver@ucsd.edu Website: http://www.biology.ucsd.edu/labs/traver/

RESEARCH INTERESTS

Dr. David Traver’s research laboratory is interested in the development of the blood-forming, or hematopoietic, system in the vertebrate embryo. Most of their studies are aimed at understanding how the hematolymphoid system arises in the zebrafish embryo from the first hematopoietic stem cells. They are leveraging the many advantages that the zebrafish system offers to study the ontogeny of hemotopoiesis and immunity. These include the easy visualization of blood cells in the translucent embryo and the ability to dissect genetically the pathways important for blood cell specification, maintenance and function.

SELECTED PUBLICATIONS FROM 2010 1. Bertrand, J.Y., Cisson, J.L., Stachura, D.L., and D. Traver. 2010. Notch signaling distinguishes two waves of definitive

hematopoiesis in the zebrafish embryo. Blood. 115:2777-2783. 2. Bertrand, J.Y., N.C. Chi, B. Santoso, S. Teng, D.Y.R. Stainier, and D. Traver. 2010. Hematopoietic stem cells derive

directly from aortic endothelium during development. Nature. 464:108-111. 3. Lugo-Villarino, G., K.M. Balla, D.L. Stachura, K. Banuelos, M.B.F.Werneck, and D. Traver. 2010. Identification of

dendritic antigen-presenting cells in the zebrafish. PNAS. 107:15850-15855. 4. Balla, K.M., Lugo-Villarino, G., J. Spitsbergen, D.L. Stachura, Y. Hu, K. Banuelos, O. Romo-Fewell, R.V. Aroian, and D.

Traver. 2010. Eosinophils in the zebrafish: Prospective isolation, characterization and eosinophilia induction by helminth determinants. Blood. 116:3944-3954.

Awards and Honors

UCSD Faculty Excellence Award and Jacobs Endowed

Chair in Bioengineering, 2008

Awards and Honors

New Faculty Award, California Institute for

Regenerative Medicine, 2008 Innovator Award, Alex’s Lemonade Stand Foundation, 2010 Director, International Society for Experimental Hematology, 2010

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Ajit Varki, M.D. Distinguished Professor of Medicine and Cellular and

Molecular Medicine Associate Dean of Physician-Scientist Training Co-Director, Glycobiology Research and Training Center

(GRTC) Co-Director, UCSD/Salk Center for Academic Research

and Training in Anthropogeny (CARTA)

Phone: (858) 534-2214 E-Mail: a1varki@ucsd.edu Website: http://cmm.ucsd.edu/Lab_Pages/varki/index.html

RESEARCH INTERESTS

• Glycobiology, Evolutionary Biology, Genetics, Microbiology, Immunology, Cancer Biology, Human Evolution

RESEARCH SUMMARY

Dr. Ajit Varki’s interests focus on the sialic acid family of sugar molecules that are found at the outermost position on the glycan chains of all vertebrate cell surfaces and glycoproteins. Current projects are relevant to the roles of sialic acids in Viral and Bacterial Infectivity, the Regulation of the Immune Response, the Initiation and Progression of Tumors and Unique Aspects of Human Evolution. Of particular interest are multiple differences in sialic acids between humans and our closest evolutionary cousins, the great apes. These differences are signatures of the multiple cellular and molecular events that occurred during the last few million years of human evolution.

SELECTED PUBLICATIONS 1. Ghaderi, D., et al. 2010. Implications of the presence of N-glycolylneuraminic acid in recombinant therapeutic

glycoproteins. Nat. Biotechnol. 28:863-7. 2. Taylor, R.E., et al. 2010. Novel mechanism for the generation of human xeno-autoantibodies against the nonhuman sialic

acid N-glycolylneuraminic acid. J. Exp. Med. 207:1637-46. 3. Surolia et al.: Functionally defective germline variants of sialic acid acetylesterase in autoimmunity. Nature. 466:243-7. 4. Varki, A. 2009. Uniquely Human Evolution of Sialic Acid Genetics and Biology. Proc. Natl. Acad. Sci.. 107 (S2): 8939-

8946. 5. Varki, A. 2009. Human Uniqueness and the Denial of Death. Nature. 460:684.!!

Karl Willert, Ph.D. Assistant Professor of Cellular and Molecular Medicine Director, UCSD Human Embryonic Stem Cell Core Facility Phone: (858) 822-3235 E-Mail: kwillert@ucsd.edu Website: http://stemcells.ucsd.edu/facility-hesc.asp

RESEARCH INTERESTS

• Wnt signal transduction and biochemistry • Stem cell proliferation and differentiation • Cellular microarray technology

RESEARCH SUMMARY

The main focus of Dr. Karl Willert’s lab is to understand how the extracellular environment regulates cell fate choices. His lab utilizes human pluripotent stem cells—both embryonic and induced pluripotent stem cells (hESC and iPSC)—to explore early developmental fate choices with particular emphasis on the role of the Wnt signaling pathway. A long-term goal of the Willert lab is to direct the differentiation of pluripotent stem cells into specific lineages. To this end, the Willert lab together with Dr. Shu Chien in Bioengineering has developed a novel cellular microarray technology, which allows for the screening of the effect of thousands of combinations of biological molecules on any cellular process of interest. Notably, the effect of Wnt proteins, which are potent regulators of stem cell fate, is dependent on the composition of the entire cellular environment.

SELECTED PUBLICATIONS

1. Brafman, D., Chang, C.-W., Fernandez, A., Willert, K., Varghese, S., Chien, S. 2010. Long-term human pluripotent stem cell self-renewal on synthetic polymer surfaces. Biomaterials. 31:9135-9144.

2. Brafman, D., Shah, K., Fellner, T., Chien, S., and Willert, K. 2009. Defining long-term maintenance conditions of human embryonic stem cells with arrayed cellular microenvironment technology. Stem Cells Dev. 8:1141-54.

Awards and Honors Member, Institute of Medicine Member, American Academy of Arts and Sciences Member, Association of American Physicians Member, American Society for Clinical Investigation

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Gene Yeo, Ph.D. Assistant Professor of Cellular and Molecular Medicine Investigator, Institute for Genomic Medicine Phone: (858) 534-9321 E-Mail: geneyeo@ucsd.edu Website: http://yeolab.ucsd.edu

RESEARCH INTERESTS

• Genome-wide analysis of RNA processing modulated by RNA binding proteins in development and disease. • Molecular Basis of Mental and Neurological disorders (Autism, Fragile X, ALS)

RESEARCH SUMMARY

The main focus of Dr. Gene Yeo’s lab is to understand the impact of RNA processing and regulation in cancer, development, mental and neurological disorders. The Yeo lab currently leverages its core strengths in systems and computational biology, molecular biology, biochemistry and genomics to study the function of specific RNA binding proteins using pluripotent human stem cells, mice models and other model organisms of development (C. elegans) and regenerative medicine (Planaria).

SELECTED PUBLICATIONS FROM 2010 1. Zisoulis, D.G., Lovci, M.T., Wilbert, M.L., Hutt, K.R., Liang T.Y., Pasquinelli, A.E., Yeo, G.W. 2010. Comprehensive

discovery of endogeneous Argonaute binding sites in Caenorhabditis elegans. Nat. Struct. Mol. Biol. 17:173-9. 2. Wilbert M.L, Yeo, G.W. Genome-wide approaches in the study of microRNA biology. 2010. Wiley Interdiscip Rev Syst Biol

Med. 3. Nelles, D.A., Yeo, G.W. Alternative splicing in stem cell self-renewal and differentiation. 2010. Adv Exp Med Biol. 695:92-

104. 4. Hinton A., Afrikanova I, Wilson M, King C.C., Maurer B., Yeo, G.W., Hayek A., Pasquinelli, A.E. 2010. A distinct

microRNA signature for definitive endoderm derived from human embryonic stem cells. Stem Cells Dev. 19:797-807.

Huilin Zhou, Ph.D. Associate Professor of Cellular and Molecular Medicine Associate Member, Ludwig Institute for Cancer Research Phone: (858) 534-7808 E-Mail: huzhou@ucsd.edu Website: http://licr.ucsd.edu/labs/proteomic_biology/

RESEARCH INTERESTS

• How cells sense and respond to DNA damage • Quantitative proteomics

RESEARCH SUMMARY

The laboratory, headed by Dr. Huilin Zhou, is interested in understanding how cells sense and respond to DNA damage. They focus on three areas of investigation. First, they have reconstituted the entire kinase cascade in vitro and studied how various adaptor proteins promote DNA damage checkpoint activation. The long-term goal is to elucidate how the checkpoint proteins work together to mount a robust response to a single DNA lesion in the genome. Second, they have developed a quantitative phospho-proteomics technology to analyze phosphorylation-mediated signal transduction pathways. Using this technology, they performed a proteome-wide analysis and discovered many new substrates of DNA damage checkpoint kinases in yeast. These results provide the foundation to understand how these kinases control the DNA damage response. Third, the DNA damage checkpoint kinases have a critical role in telomere maintenance and DNA repair, they are further investigating the regulation and function of those kinase substrates implicated in telomere maintenance and DNA repair.

SELECTED PUBLICATIONS FROM 2010 $, Chen, S.H., Albuquerque, C.P., Liang, J., Suhandynata, R.T. and Zhou, H. 2010. A Proteome-wide analysis of kinase-

substrate network in the DNA damage response. J. Biol. Chem. 284:18593-604. &, Zhou, H., Albuquerque, C.P., Liang, J, Suhandynata, R.T., Weng, S. 2010. Quantitative phosphoproteomics: New

technolologies and applications in the DNA damage response. Cell Cycle. 9(17).

Awards and Honors Fellow, The Alfred P. Sloan Foundation

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New and Ongoing Research Initiatives ! THE INSTITUTE FOR GENOMIC MEDICINE Kang Zhang, Director Al La Spada, Bruce Hamilton, Associate Directors http://igm.ucsd.edu/

Founded by the UCSD School of Medicine and the UCSD Skaggs School of Pharmacy and Pharmaceutical Sciences, the UCSD Institute for Genomic Medicine is a center of excellence for organizing the multi-disciplinary resources necessary to effectively translate the discoveries of genetic and genomic research from “bench to bedside”. The IGM aims to link clinical and genomic information to facilitate personalized health care. By combining UCSD’s expertise in Genetics, Disease Biology, and Clinical Practice with its strengths in Computer Science, Bioinformatics, and Systems Biology, the IGM is uniquely positioned to support all activities along the continuum of genomic medicine. In addition, the Institute will help bring resources and recognition to the campus in support of genomic medicine. The institute is led by Dr. Kang Zhang, Professor of Ophthalmology, along with Associate Directors Bruce Hamilton and Albert La Spada, both of CMM. Dr. Hamilton facilitates interactions and ensures formation of teams within IGM to address basic research opportunities and foster a rigorous and productive training environment in Genetics and Genomics among UCSD PhD programs. Dr. Hamilton also maintains partnerships with academic departments and established degree programs to facilitate and enhance interdisciplinary educational programs. This team is rounded out by Associate Director Dr. La Spada who coordinates efforts for subject enrollment, clinical sample collections and medical teaching. Dr. La Spada maintains partnerships with clinical enterprise offices and IRB to enhance the impact of IGM on clinical applications. He also ensures vibrant clinical and translational training in Human Genetics and Genomic Medicine for medical students and clinical fellows.

The 18 members of the Institute include 8 from CMM: Xiang-Dong Fu, Bing Ren, Gene Yeo, Christopher Glass, Albert LaSpada, Richard Kolodner, Jonathan Sebat, and Bing Ren. The Institute’s Advisory Committee, chaired by Dean for Scientific Affairs Gordon Gill, includes Joan Heller-Brown, Chair/Pharmacology; Shu Chien, Director/Institute of Engineering in Medicine; Don Cleveland, Chair/CMM; Gabriel Haddad, Chair/Pediatrics; Lewis Judd, Chair/Psychiatry; Susan Taylor, Chair/Health Sciences Research Council, and Palmer Taylor, Dean, Skaggs School of Pharmacy and Pharmaceutical Sciences.

The highlight of 2010 was the IGM Inaugural Symposium (see poster above). Over 200 faculty, students, and local scientists attended.

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Research Initiatives (continued)

GLYCOBIOLOGY AND RESEARCH TRAINING CENTER (GRTC) Jeffry Esko, Co-Director • Ajit Varki, Co-Director http://grtc.ucsd.edu/

The Glycobiology Research and Training Center underwent its second 5-year review and received another outstanding report. The Center continues to adhere to its original objectives to facilitate and enhance glycobiology research and training among University of California faculty with the minimum possible paperwork and bureaucracy. During the period under review, the membership increased across UC campuses to 80 members. The interdisciplinary nature of the GTRC is reflected by its membership across departments at UCSD including SOM, SIO, CMM, Biology, and Chemistry, with additional members throughout California. Communication among the members has been maintained through the GRTC web site (http://grtc.ucsd.edu) and through the annual San Diego Glycobiology Symposium (http://grtc.ucsd.edu/sdgs.html). Another major accomplishment of the GTRC was the publication of a 2nd edition of Essentials of Glycobiology, which has become the standard reference in the field, and is the first example of a successful “Open Access” textbook (http://www.ncbi.nlm.nih.gov/books/NBK20709/). The GRTC also houses the Glycotechnology Core, which provides state of the art analyses of all classes of glycans to members of the GRTC, the UCSD community and other UC campuses, as well as to investigators at campuses across the United States and in the private sector.

The Co-Directors along with Richard Gallo and Victor Nizet recently applied for a Program of Excellence program project grant in response to an RFA from NHLBI. The grant received top scores and will provide resources for research and training experiences in glycobiology for post-doctoral fellows. Based upon the accomplishments of the GTRC, the faculty review committee unanimously recommended continuation of this ORU and reappointment of both co-directors for another 5-year term.

STEM CELL RESEARCH PROGRAM Lawrence Goldstein, Director • Karl Willert, Director, hESC Core Facility http://stemcells.ucsd.edu/ Program Overview

The UC San Diego Stem Cell Program works to create and maintain scientific leadership in stem cell biology, medicine and ethics. The Program works through existing departments and units campus-wide to obtain grants, recruit faculty and researchers, develop curricular offerings and public education, sustain shared research facilities, and meet the changing needs of researchers in this field. Faculty members participating in the Stem Cell Program are drawn from a wide variety of specialties including neurobiology, medicine, embryology, development, neuroscience, cell signaling, cell biology, bioinformatics, and engineering. Their research is highly interdisciplinary and utilizes a variety of genomic, cellular, animal model, and in vitro approaches to study various aspects of stem cells at the level of molecular, cellular, tissue and organ regeneration and differentiation.

The UCSD Stem Cell Program gains support from excellent ongoing relationships of shared interests, mutual education, and scientific collaborations with scientists of the Sanford Stem Cell Consortium member institutions: The Salk Institute, the Scripps Research Institute, and the Sanford Burnham Institute for Biomedical Research. The UCSD Stem Cell Program operates the Human Embryonic Stem Cell Core Facility (HESCCF), providing training, and shared resources to the UCSD community and to the Sanford Consortium.

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Research Initiatives (continued)

CENTER FOR ACADEMIC RESEARCH & TRAINING IN ANTHROPOGENY (CARTA) Ajit Varki, Director • Pascal Gagneux, Associate Director http://carta.anthropogeny.org/ !

CARTA is spearheaded by CMM faculty member Dr. Ajit Varki, who co-directs this campus wide organized research unit with Dr. Margaret Schoeninger (UCSD Anthropology) and Dr. Fred H. Gage (Salk Institute). CMM faculty member Dr. Pascal Gagneux acts as Associate Director.

CARTA has been profiled in Science in April 2010$. CARTA has organized three widely advertised public

symposia in 2010. 1. ”The Evolution of Human Biodiversity” The

distribution and nature of human genetic and phenotypic variation were discussed and contrasted with that of “great apes”.

2. “Early Hominids”. Members of the research team responsible for finding and analyzing the 4.5 million year old Ardipithecus ramidus hominid as well as other prominent paleoanthropoligists discussed evidence for early hominid evolution.

!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!1 Cohen J. 2010 Chimpanzee research today. Cutting to the bone

of human origins. Science. 328(5974):43.

3. “The Evolution of Human Altruism” The pro-social tendencies of our species and their evolutionary origins were discussed. All three public symposia were very well attended (300 to 700 people) and UCSD TV has televised each presentation. Web casts are accessible via the CARTA website (http://carta.anthropogeny.org/symposia/past/list), the UCSD TV CARTA Series Website (http://www.ucsd.tv/carta/) and You tube. There have been tens of thousands of hits for these presentations.

A new graduate specialization in Anthropogeny with seven participating graduate programs has been initiated and the first three graduate students, one each from Biomedical Sciences, Cognitive Sciences and Linguistics have enrolled. Ten graduate students from six different graduate programs have repeatedly participated in the CARTA symposia during 2010.

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CMM Contracts and Grants

EXCEPTIONAL AWARDS TO CMM FACULTY

CIRM AWARD: TRANSLATIONAL RESEARCH STUDIES: $5.8 million Two scientists at the University of California, San Diego School of Medicine – Catriona Jamieson, MD, PhD, and Alysson Muotri, PhD – have received grants from the California Institute for Regenerative Medicine (CIRM) for stem cell research. Purpose: The approximate $1.5 million awarded to Alysson Muotri, PhD, assistant professor of Cellular and Molecular Medicine, is to help design a future drug-screening system for autism spectrum disorders (ASD) that employs human neurons. Muotri and colleagues are using induced pluripotent stem cells derived from skin cells taken from patients with autism spectrum disorders like Rett Syndrome to create “autistic” neurons. “These are experiments that have never been possible before,” said Muotri. “We hope they will help us better understand the causal molecular mechanisms of ASD, find possible biomarkers for the disease, and identify specific therapeutic targets.” The grants are part of $67 million in Early Translation II Awards announced by CIRM today, which are designed to move research out of the lab and into the clinic.

THE BETA CELL BIOLOGY CONSORTIUM: $5 million Purpose: Type 1 Diabetes Research at UC San Diego Gets $5 Million Boost. Maike Sander, MD, associate professor of pediatrics and cellular & molecular medicine at the University of California, San Diego School of Medicine has been awarded nearly $5 million by the Beta Cell Biology Consortium (BCBC) to lead an interdisciplinary team in cell therapy research for type 1 diabetes. The grant is shared with Karl Willert, PhD, Director of the UCSD Human Stem Cell Core Facility.

ARRA NIH-NINDS RESEARCH CHALLENGE AWARD: $1 million Purpose: “Human Stem Cell Model of Niemann Pick Type C awarded to Larry Goldstein, PhD. The team will create the first human neuronal model of Niemann Pick type C1 from human embryonic stem cells and human induced pluripotent stem cells. They will use control and NPC1 human neurons to study the kinetics of cholesterol trafficking in NPC1 and the role of cholesterol in neuronal survival and regeneration. This work will shed important light on an important childhood neurodegenerative disease and on Alzheimer’s disease as well.

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CMM Contracts and Grants (continued)

EXCEPTIONAL AWARDS TO CMM FACULTY NIH ROADMAP’S EPIGENOMES PROGRAM $16,600,000

Purpose. The NIH five-year grant will support the San Diego Epigenome Center at the Ludwig Institute for Cancer Research at UCSD. CMM’s Bing Ren is Director of this Center, only one of four established nationwide by the NIH Epigenomics Program, an initiative developed to study stable genetic modifications that affect and alter the behavior of genes across the human genome.

CIRM DISEASE TEAM RESEARCH AWARD FOR A CELL $11,000,000 BASED THERAPY FOR ALS

Purpose. The CIRM-funded multidisciplinary teams of California researchers. Larry Goldstein and Don Cleveland are co-principal investigators on a $11 million grant to develop, together with Prof. Martin Marsala of Anesthesiology and Sam Pfaff at the Salk Institute, a novel cellular therapy for ALS.

CENTER FOR ACADEMIC RESEARCH AND TRAINING $3,000,000 IN ANTHROPOGENY (CARTA)

Purpose. The establishment of CARTA as a campus ORU, Ajit Varki as its first co-director. The Center will coordinate and promote transdisciplinary research in anthropogeny, i.e., explaining the origin of humans, in fields ranging from molecular biology and neurosciences to anthropology and linguistics. The G. Harold & Leila Y. Mathers Foundation has committed $3 million over 3 years to launch the new center.

NIH NEW INNOVATOR AWARD $1,500,000

Purpose. The NIH awarded Alysson Muotri, one of five UCSD researchers, a new innovator award, $1.5 million grant over five years. Muotri’s project, “Modeling Autism with Human Pluripotent Cells” is a novel approach to study autism.

SHARED INSTRUMENTATION AWARDS $1,419,761

Purpose. The NCRR Shared Instrument Grant program solicits applications from groups of NIH-supported investigators to purchase or upgrade commercially available instruments that cost at least $100,000. The maximum award is $500,000. Types of instruments supported include: confocal and electron microscopes, biomedical imagers, mass spectrometers, DNA sequencers, biosensors, cell sorters, X-ray diffraction systems, and NMR spectrometers among others. In 2009, CMM investigators competed successfully for funding to purchase:

LTQ Linear Ion Trap Mass Spectrometer Jeffrey Esko $420,055 FEI Tecnai G2 Spirit BioTwin

Transmission Electron Microscope Marilyn Farquhar $499,706 Illumina Genome Analyzer Xiang-Dong Fu $500,000

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CMM Contracts and Grants (continued)

CMM FACULTY COMPETE FOR $4 MILLION (YEAR 2)

FROM PRESIDENT OBAMA’S AMERICAN RECOVERY AND

REINVESTMENT ACT STIMULUS FUNDING

CHALLENGE

GRANTS D. Cleveland NINDS ALS Therapies and Genomics for Mutant TDP-

43 and TLS/FUS $999,148

CHALLENGE

GRANTS L. Goldstein NINDS Human Stem Cell Model of Niemann

Pick Type C

$1,000,000

GRAND

OPPORTUNITY GRANTS

D. Cleveland NINDS Delivery of Therapeutic Genes in Motor Neuron Disease

$342,438

J. Esko NCRR Shared Instrumentation Grant: LTQ Linear Ion Trap Mass Spectrometer (S10)

$420,055 SHARED

INSTRUMENTATION

GRANTS

M. Farquhar NCRR FEI Tecnai G2 Spirit BioTWIN Transmission Electron Microscope (S10)

$499,706

RESEARCH CAREER

GRANTS S. Hedrick NIAID Control of lymphocyte homeostasis by Foxo

transcription factors $772,500

TOTAL ARRA BUDGETS (Direct + Indirect): $4,033,847

Institute and Centers Abbreviations: NIAID, National Institute of Allergy and Infectious Diseases; NINDS, National Institute of Neurological Disorders and Stroke; NCRR, National Center for Research Resources

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CMM Contracts and Grants (continued)

CMM FACULTY RESEARCH FUNDING

FISCAL YEARS 2009 & 2010

*Six CMM faculty members are Ludwig Investigators.

CMM RESEARCH FUNDING 2005 - 2010

CMM Administered Research Fiscal Year

2009 Fiscal Year

2010 % change

Fed & Non-federal Awards: 14,915,694 22,750,650 52%

Gifts & Private foundation Awards: 1,430,725 3,455,106 141%

Total CMM Research funding through UCSD: 16,346,419 26,205,756 60%

Outside funding to CMM faculty awarded through the Ludwig Institute* : 9,527,602 9,812,403 3%

Total CMM Faculty Research Funding: 25,874,021 36,018,159 39%

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2010 CMM/LICR Seminar Series

DATE! SPEAKER INSTITUTION TITLE

01/07/10! Jef D. Boeke, Ph.D.!Director of the High Throughput Biology Center

John Hopkins University School of Medicine!

Retrotransposition of Natural and Synthetic L1 (LINE-1) Elements.

01/14/10! Kim Orth, Ph.D.!Associate Professor of Molecular Biology

University of Texas Southwestern Medical Center!

Black Spot, Black Death, Black Pearl: The Tales of Bacterial Effectors.!

01/21/10! Susan S. Suarez, Ph.D. !Professor of Biomedical Sciences

Cornell University ! Interactions of Mammalian Sperm with the Female Reproductive Tract.!

02/04/10! Marianne Bronner-Fraser, Ph.D.!Professor of Biology

Caltech! Gene Regulatory Networks Underlying Neural Crest Formation.!

02/18/20! John J.M. Bergeron, Ph.D.!Professor of Anatomy and Cell Biology

McGill University! A Perspective on Golgi Apparatus Structure and Function.!

02/25/10! Gail Mandel, Ph.D.!Professor of Biochemistry and Molecular Biology

Oregon Health and Science University Howard Hughes Medical Institute

Repressors and Gila: Life Support for Neurons.!

03/04/10! Juan S. Bonifacino, Ph.D.!Director of Cell Biology and Metabolism Program

National Institutes of Health! Traffic of the Amyloid Precursor Protein Mediated by the AP-4 Complex.!

03/11/10! Pamela Silver, Ph.D.!Professor of Systems Biology

Harvard Medical School! Designing Cellular Memory, Metabolism and Mutualism.!

04/01/10! Angelika Amon, Ph.D.!Professor of Biology Howard Hughes Investigator

Massachusetts Institute of Technology!

Consequences of Aneuploidy.!

04/08/10! Alan D. D’Andrea, M.D.!Professor of Radiation Oncology

Harvard Medical School, Dana-Farber Cancer Institute!

Regulation of DNA Repair by Ubiquitnation and SUMOylation.!

04/15/10! Hannes E. Buelow, Ph.D.!Assistant Professor of Genetics and Neuroscience

Albert Einstein College of Medicine!

A Function for Specific Heparan Sulfate Modifications in Development and Disease.!

04/22/10! Jeremy Reiter, M.D., Ph.D.!Assistant Professor of Biochemistry and Biophysics

University of California, San Francisco!

Primary Cilia Transduce Hedgehog Signals in Vertebrate Development and Cancer.!

04/29/10

Victor Ambros, Ph.D. Professor of Genetics

University of Massachusetts Medical School

MicroRNA’s in Development and Disease.

05/06/10 Ali Shilatifard, Ph.D. Investigator

Stowers Institute for Medical Research

Lessons Learned from Yeast about Human Leukemia.

05/13/10 Haifan Lin, Ph.D. Professor of Cell Biology & Genetics

Yale University A Novel piRNA-Mediated Epigenetic Mechanism Related to Stem Cells.

05/20/10 Tom Misteli, Ph.D. Cell Biology of Genomes Group Senior Investigator

National Cancer Institute, National Institutes of Health

Nuclear Architecture, Aging and Stem Cells.

05/27/10 Kang Shen, Ph.D. Assistant Professor of Biology and Pathology

Stanford University Extrinsic and Intrinsic Regulators of Synapse Formation in C. elegans.

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2010 CMM/LICR Seminar Series (continued)

DATE! SPEAKER! INSTITUTION! TITLE!

09/30/10 David L. Spector, Ph.D. Director of Research

Cold Spring Harbor Laboratory Long Non-Coding RNAs Involved in Nuclear Organization and Function.

10/05/10 Sandra L. Schmid, Ph.D. Professor and Chair Department of Cell Biology

The Scripps Research Institute Complexity and Regulation of Clathrinmediated Endocytosis.

10/12/10 Gideon Dreyfuss, Ph.D.

-../0!12334.!53267..23!26!

842097:4.;3<!/=>!842?9<.4.!

Howard Hughes Investigator

University of Pennsylvania School of Medicine

RNPs: Instruments of Global Transcriptome Regulation.

10/21/10 Anne Villeneuve, Ph.D. !Professor of Genetics and Developmental Biology

Stanford University School of Medicine

Chromosome Dynamics During C. elegans Meiosis.!

10/28/10! Vicki Chandler, Ph.D.!Regent’s Professor Department of Plant Sciences and Molecular & Cellular Biology

University of Arizona! Paramutation: Epigenetic Silencing Across Generations.!

11/14/10! Gerald Manning, Ph.D.!Director, Salk Bioinformatics

Salk Institute for Biological Studies

Unlocking Biological Secrets and History with Genome Sequences.!

11/18/10! Trudi Schupbach, Ph.D. Professor of Molecular Biology Howard Hughes Investigator

Princeton University! EGF Receptor Activation and Follicle Cell Differentiation in Drosophila.!

12/02/10! Rama Ranganathan, Ph.D. Professor of Pharmacology

University of Texas Southwestern Medical Center Green Center for Systems Biology

The Evolutionary Design of Protein!

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CMM Administrative Staff !

BUSINESS OFFICE OPERATIONS

DENA REA Department Business Officer University Service: Since 1978

CMM Service: Since 2006

FISCAL MANAGEMENT

RINA HLIFKA Senior Fiscal Analyst

University Service: 1991-1998, 2004-present CMM Service: Since 1991

SUSAN VALLE Fund Management Specialist University Service: Since 1994

CMM Service: Since 1995

KRISTY HINDLE Fund Management Specialist University Service: Since 1997

CMM Service: Since 1997

GREGG FASTRING Fund Management Specialist

University Service: 1996-2000, 2004-present CMM Service: Since 1996

PEILI HSU Fund Management Specialist University Service: Since 2006

CMM Service: Since 2008

HUMAN RESOURCES

CHRISTINE MATA Human Resources Manager

University Service: Since 2002 CMM Service: Since 2006

IT SERVICES

TOD KUYKENDALL Programmer Analyst

University Service: Since 2005 CMM Service: Since 2005

PROCUREMENT,

SEMINAR SERIES & ADMINISTRATION

NADIA PRYADILOVA Administrative Assistant

University Service: Since 2006 CMM Service: Since 2007

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Postdoctoral Fellows in CMM !

Ali, Syed Raza Hannover Medical School, Ph.D. 2005 (Varki Laboratory) Alves, Bryce N. University of Nevada, Ph.D. 2009 (Hedrick Laboratory) Axelsson, Jakob Lund University, Ph.D. 2008 (Esko Laboratory) Bahmanyar, Shirin Stanford, Ph.D. 2008 (Oegema Laboratory) Baldo, Veronica Milano-Bicoca University, Ph.D. 2009 (Zhou Laboratory) Banda, Kalyan Christian Medical School, M.D. 2008 (Varki Laboratory) Bauer, Matthieu Institut Gustav Roussy, Ph.D. 2010 (Willert Laboratory) Beas, Anthony UCSD, Ph.D. 2009 (Farquhar Laboratory) Belzile, Jean-Philippe University of Montreal, Ph.D. 2010 (Spector Laboratory) Benner, Chris UCSD, Ph.D. 2009 (Glass Laboratory) Bergfeld, Anne Katrin Hannover Medical School, Ph.D. 2009 (Varki Laboratory) Bertrand, Julien Y. University of Paris, Ph.D. 2005 (Traver Laboratory) Bhandari, Deepali Loyola University, Ph.D. 2009 (Ferro-Novick Laboratory) Brafman, David UCSD, Ph.D. 2009 (Willert Laboratory)

Cadwallader, Adam University of Utah, Ph.D. 2007 (Esko Laboratory) Campbell, Chris UC San Francisco, Ph.D. 2008 (Desai Laboratory) Carvalho, Ana University of Edinburgh, Ph.D. 2005 (Oegema Laboratory) Cetin, Bulent University of Oxford, Ph.D. 2009 (Cleveland Laboratory) Chen, Irene Lee UCSD, Ph.D. 2008 (Hedrick Laboratory) Chen, Sheng-Hong UCSD, Ph.D. 2009 (Zhou Laboratory) Chen, Shu Liang Wayne State University, Ph.D. 2008 (Ferro-Novick Laboratory) Cherrambathur, Danya University of California, Davis, Ph.D. 2008 (Desai Laboratory) Clements, Wilson University of Washington, Ph.D. 2004 (Traver Laboratory) Cohen, Miriam Weizmann Institute of Science, Ph.D. 2005 (Gagneux Laboratory) Crittenden, Alyssa UCSD, Ph.D. 2009 (Varki Laboratory) Crotti, Andrea Open University, London, Ph.D. 2008 (Glass Laboratory) Da Cruz, Sandrine University of Geneva, Ph.D. 2006 (Cleveland Laboratory) De Albuquerque, Claudio Ponte UCSD, Ph.D. 2010 (Zhou Laboratory)

De Groot, Christian ETH Zurich, Ph.D. 2010 (Desai Laboratory) Dejean, Anne University of Toulouse, Ph.D. 2006 (Hedrick Laboratory) Denicourt, Catherine University of Montreal, Ph.D. 2003 (Dowdy Laboratory) Distel, Martin TU Munchen, Ph.D. 2010 (Traver Laboratory) Ditsworth, Dara University of Pennsylvania, Ph.D. 2008 (Cleveland Laboratory) Du, Tingting University of Mass, Ph.D. 2008 (Ren Laboratory) Dumont, Julien University of Paris, Ph.D. 2006 (Desai Laboratory) Durose, Jenny UCSD, Ph.D. 2009 (Spector Laboratory) Espeut, Julien Centre de Recherche de Biochimie Moleculare, Montepellier, Ph.D. 2007 (Desai Laboratory) Espinoza, Celso University of Colorado, Ph.D. 2007 (Ren Laboratory) Fachinetti, Daniele University of Milan, Ph.D. 2007 (Cleveland Laboratory) Foloc, Diego University of Cordoba, Argentina Ph.D. 2003 (Desai Laboratory) Fox, Kristi University of California, Irvine, Ph.D. 2007 (Fu Laboratory)

Postdoctoral Fellows in CMM (continued)

! (%!

Fulai, Jin UCLA, Ph.D. 2007 (Ren Laboratory) Garcia-Marcos, Mikel University of Basqu Country, Ph.D. 2005 (Farquhar Laboratory) Gassmann, Reto University of Edinburgh, Ph.D. 2005 (Desai Laboratory) Ghaderi, Darius Free University of Berlin, Ph.D. 2006 (Varki Laboratory) Gogoi, Khirud Pune University, Ph.D. 2009 (Dowdy Laboratory) Gomez-Cabrero Segura, Azucena University of Barcelona, Ph.D. 2006 (Dowdy Laboratory) Gordst, Philip University of Leuven, Ph.D. 2010 (Esko Laboratory) Green, Rebecca University of California, Davis, Ph.D. 2005 (Oegema Laboratory) Gros, Edwige E. University of Montpellier, Ph.D. 2008 (Dowdy Laboratory) Hagopian, Jonathan C. UCSD, Ph.D. 2009 (Dowdy Laboratory) Han, Joo-Seok

Seoul National University, Ph.D. 2002

(Cleveland Laboratory) Hattersley, Neil University of Dundee, Ph.D. 2010 (Desai Laboratory) Hess, Rodrigo

San Raffaele Scientific Institute, Ph.D. 2009

(Hedrick Laboratory) Holland, Andrew Manchester University, Ph.D. 2006 (Cleveland Laboratory)

Hutt, Kasey

UCSD, Ph.D. 2008

(Yeo Laboratory) Israelson, Adrian

Ben Gurion Univ. of the Negev, Israel, Ph.D. 2006

(Cleveland Laboratory) June, Ron

University of California, Davis, Ph.D. 2007

(Dowdy Laboratory) Kaikkonen, Minna Unelma

University of Kuopio, Ph.D. 2008

(Glass Laboratory) Karavani, Vered

Tel Aviv University, Ph.D. 2005

(Varki Laboratory) Kogiso, Tomomi

Tokyo Women's College, M.D. 2005

(Dowdy Laboratory) Kordasiewicz, Holly

University of Minnesota, Ph.D. 2006

(Cleveland Laboratory) Kraynyak, Kimberly University of Pennsylvania, Ph.D. 2009

(Spector Laboratory) Krona, Cecilia

University of Gothenburg, Sweden, Ph.D. 2006

(Cleveland Laboratory) Lagier-Tourenne, Clotilde

Strasbourg University, M.D./Ph.D. 2007

(Cleveland Laboratory) Lamanna, William Christopher

University of Göttingen, Ph.D. 2008

(Esko Laboratory) Lan, Weijie

University of Virginia, Ph.D. 2006

(Cleveland Laboratory) Lee, Yoonsung

Duke University, Ph.D. 2009

(Traver Laboratory) Li, Yan City of Hope, Ph.D. 2009 (Ren Laboratory)

Ling, Shuo-Chien

University of Illinois, Ph.D. 2005

(Cleveland Laboratory) Liu, Dongmei Wayne State University, Ph.D. 2010 (Novick Laboratory) Lo, I-Chung National Chung Kung University, Ph.D. 2009 (Farquhar Laboratory) Lofling, Jonas

Karolinska Institutet, Sweden, Ph.D. 2006

(Varki Laboratory) Ma, Fang Chongqing Medical University, Ph.D. 2006

(Gagneux Laboratory) Massirer, Katlin UCSD, Ph.D. 2009

(Yeo Laboratory) Meade, Bryan UCSD, Ph.D. 2010 (Dowdy Laboratory) Menon, Shekar

University of Cincinnati, Ph.D. 2004

(Ferro-Novick Laboratory) Misaki, Taro

Hamamatsu University, Ph.D. 2009

(Farquhar Laboratory) Nathanson, Jason L. UCSD, Ph.D. 2008

(Yeo Laboratory) Nechemia-Arbely, Yael Hebrew University, Ph.D. 2010

(Cleveland Laboratory) Olson, Sarah

UCSD, Ph.D. 2005

(Oegema Laboratory) Palm Apergi, Caroline

Stockholm University, Ph.D. 2008

(Dowdy Laboratory) Pandit, Shatakshi (Sakshi)

University of Kentucky, Ph.D. 2007

(Fu Laboratory)

Postdoctoral Fellows in CMM (continued)

! ($!

Parone, Philippe

Cambridge University, Ph.D. 2005

(Cleveland Laboratory) Pearce, Oliver M. University of Oxford, Ph.D. 2007

(Varki Laboratory) Polymeniou, Magdalini

University of Zurich, Ph.D. 2005

(Cleveland Laboratory) Presente, Asaf

University of Penn, Ph.D. 2005

(Dowdy Laboratory) Qiu, Jinsong

Fordham University, Ph.D. 2009

(Fu Laboratory)

Rodrigues, Elizabeth UCSD, Ph.D. 2010 (Goldstein Laboratory) Romanoski, Casey E. UCLA, Ph.D. 2010 (Glass Laboratory) Ross, Jason University of Kansas, Ph.D. 2010 (Willert Laboratory) Salazar, Desiree University of California, Irvine, Ph.D. 2010 (Cleveland Laboratory) Sanders, Rebecca UCSD, Ph.D. 2009 (Spector Laboratory) Sarrazin, Stephane

Joseph Fourier University, Ph.D. 2007

(Esko Laboratory) Seamen, Emylie University of Colorado, Boulder, Ph.D. 2009

(Esko Laboratory) Shah, Mehul Bipinchandra

New York Medical College, M.D./Ph.D. 2006

(Farquhar Laboratory) Shapiro, Gary

University of Colorado, Ph.D. 2004

(Dowdy Laboratory)

Shen, Weiqun

Univ.of Sci. and Tech. Of China, Ph.D. 2007

(Fu Laboratory) Shen, Yin UCLA, Ph.D. 2008 (Ren Laboratory) Shibata, Norihito University of Tokyo, Ph.D. 2004 (Glass Laboratory) Smallwood, Andrea

UCLA, Ph.D. 2007

(Ren Laboratory) Soto, Paula Campos

UCSD, Ph.D. 2008

(Varki Laboratory) Spann, Nathan UCSD, Ph.D. 2005

(Glass Laboratory) Stachura, David

University of Penn, Ph.D. 2005

(Traver Laboratory) Stender, Joshua D. University of Illinois, Ph.D. 2007

(Glass Laboratory) Stevens, Deanna UCSD, Ph.D. 2011 (Desai Laboratory) Stone, Erica

UCSD, Ph.D. 2009

(Hedrick Laboratory) Sun, Shuying Stony Brook University, Ph.D. 2010 (Cleveland Laboratory) Tanaka, Yumiko

University of Tokyo, M.D/Ph.D. 2006

(Glass Laboratory) Taupin, Vanessa University Blaise Pascal Clermont-Ferrand, Ph.D. 2006

(Farquhar Laboratory) Teodorof, Carmen Gwangju Institute of Science and Technology, Ph.D. 2010 (Farquhar Laboratory)

Tong, Xiangyan (Sherry)

University of Kansas, Ph.D. 2007

(Zhou Laboratory) Tran, Karen UCSD, Ph.D. 2009 (Spector Laboratory) Van Den Berg, Arjen

University of Amsterdam, Ph.D. 2006

(Dowdy Laboratory) Varsano, Tal

Weizmann Institute of Science, Ph.D. 2004

(Farquhar Laboratory) Viscardi, Valeria UCSD, Ph.D. 2011 (Oegema Laboratory) Vitre, Benjamin

University of Rennes, Ph.D. 2008

(Cleveland Laboratory) Wang, Guoliang (Tony) University of Chicago, Ph.D. 2006 (Zhou Laboratory) Wang, Honghui Gunma University, Ph.D. 2009 (Farquhar Laboratory) Wang, Juan Tsinghua University, Ph.D. 2010 (Ferro-Novick Laboratory) Wang, Pingping

Justus-Liebig-Univ of Gissen, Ph.D. 2007

(Fu Laboratory) Wang, Xiaoxia

University of Michigan, Ph.D. 2007

(Varki Laboratory)

Weaver, Carole

University of Chicago, Ph.D. 2006

(Goldstein Laboratory) Wei, Chaoliang

Peking University, Ph.D. 2007

(Fu Laboratory) Wittamer, Valerie

Brussels University, Ph.D. 2005

(Traver Laboratory)

Postdoctoral Fellows in CMM (continued)

! (&!

Wong, Yao Northwestern University, Ph.D. 2010 (Desai Laboratory) Xie, Wei UCLA, Ph.D. 2009 (Ren Laboratory) Xu, Ding

University of North Carolina, Ph.D. 2006

(Esko Laboratory) Xue, Yuan-Chao

Wuhan University, Ph.D. 2009

(Fu Laboratory) Yamasaki, Akinori

Tokyo Institute of Technology, Ph.D. 2007

(Ferro-Novick Laboratory)

Yamasaki, Emi Mizuno

Tokyo Institute of Technology, Ph.D. 2007

(Novick Laboratory) Yoshioka, Naohisa

Osaka University, 2002

(Dowdy Laboratory) Young, Jessica E. University of Washington, Ph.D. 2009

(Goldstein Laboratory) Yue, Feng

University of South Carolina, Ph.D. 2008

(Ren Laboratory) Yuen, Karen

University of British Columbia, Ph.D. 2006

(Desai Laboratory)

Zanin, Esther

ETH Zurich, Ph.D. 2008

(Oegema Laboratory) Zhang, Dongfen

Medical College of Wisconsin, Ph.D. 2006

(Fu Laboratory) Zhou, Yu

Wuhan University, Ph.D. 2008

(Fu Laboratory) Zhou, Zhihong Central South Univ. China, Ph.D. 2003

(Fu Laboratory)

Postdoctoral Fellows who departed CMM in 2010 Canman, Julie (Oegema Laboratory) Current position: Assistant Professor, Columbia University Dammermann, Alex (Oegema Laboratory) Current position: Assistant Professor, Max Perutz Institute in Vienna, Austria Dumont, Julien (Desai Laboratory) Current Position: ANR Fellow, Curie Institute, Paris, France Espeut, Julien (Desai Laboratory) Current Position: Research Fellow, Macromolecular Biochemistry Research Center, Montpellier, France Essex, Anthony (Desai Laboratory) Current Position: Postdoctoral Fellow, Salk Institute Han, Joonhee (Fu Laboratory) Current Position: Postdoctoral Fellow, Ohio State University

Hawkins, David (Ren Laboratory) Current position: Assistant Professor, University of Washington, Seattle Ilieva, Hristelina (Cleveland Laboratory) Current position: Resident, Methodist Hospital/Baylor, Houston Kikkeri, Raghavendra (Varki Laboratory) Current position: Assistant Professor, Institute of Science Education and Research (IISER)- Pune, India Lee, Jaesung (Farquhar Laboratory) Current position: Postdoctoral Fellow, Sanford-Burnham Institute Lewellyn, Lindsay (Oegema Laboratory) Current position: Postdoctoral Fellow, University of Chicago Radulescu, Andrea (Cleveland Laboratory) Albert Einstein College of Medicine

Sinitsyna, Nadezda (Farquhar Laboratory) Current position: Postdoctoral Fellow, Institute of Allergy and Immunology, La Jolla Smolka, Marcus (Zhou Laboratory) Current position: Assistant Professor, Cornell University Stein, Lance (Varki Laboratory) Current position: Clinical Professor of Medicine, Piedmont Transplant Institute

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! ('!

Graduate Students in CMM !

Agarwal, Saurabh Indian Institute of Technology, B.A. 2003 (Ren Laboratory) Arnold, Eveline Sun University of Penn, B.A. 2006 (Cleveland Laboratory) Bush, Molly University of Wisconsin- Madison, B.A. 2005 (Oegema Laboratory) Busch, Julia University of Vienna, B.A. 2007 (Willert Laboratory) Butko, Emerald UCSD, B.A. 2006 (Traver Laboratory) Chang, Chiung-fang University of Taiwan, B.A. 2001 (Hedrick Laboratory) Chu, Eric UCSD, B.A. 2005 (Willert Laboratory) Clark, Elizabeth Purdue, B.A. 2007 (Spector Laboratory) Davies, Leela R. Brown University, B.A. 2005 (Varki Laboratory) (Davis) Nierderst, Emily Ann University of Michigan, B.A. 2004 (Goldstein Laboratory) de Albuquerque, Claudio Ponte UCSD, B.A. 2003 (Zhou Laboratory) Deng, Yiping Jilin University, B.A. 2006 (Esko Laboratory) Dixon, Jesse Princeton University, B.A. 2006 (Ren Laboratory) Foley, Erin UCLA, B.A. 2006 (Esko Laboratory)

Gonzales, Jon C. Colorado State University, B.A. 2007 (Esko Laboratory) Gregg, Christopher John Hopkins University, B.A. 2005 (Varki Laboratory) Huang, Wendy Jia Men UC Berkley, B.A. 2005 (Glass Laboratory) Huelga, Stephanie University of California, Santa Cruz, B.A. 2008 (Yeo Laboratory) Huggins, Ian University of Utah, B.A. 2008 (Willert Laboratory) Israel, Mason Brown University, B.A. 2003 (Goldstein Laboratory) Ji, Xiong Wuhan University, B.A. 2008 (Fu Laboratory) Kang, Hannah UCSD, B.A. 2010 (Hedrick Laboratory) Killian, Rhiannon Lynn Penn State University, B.A. 1995 (Goldstein Laboratory) Kim, Audrey UCSD, B.A. 2009 (Ren Laboratory) Kim, Albert UCSD, B.A. 2005 (Traver Laboratory) Kumar, Nathan (Willert Laboratory) Lam, Michael Tun Yin UC Berkley, B.A. 2003 (Glass Laboratory) Liang, Jason UCSD, B.A. 2007 (Zhou Laboratory)

Lord, Christopher L. University of Michigan, B.A. 2006 (Ferro-Novick Laboratory) Lovci, Michael UCSD, B.A. 2009 (Yeo Laboratory) Moyle, Mark BYU, B.A. 2007 (Desai Laboratory) Narasimha, Anil UC Berkley, B.A. 2007 (Dowdy Laboratory) Nelles, David University of Pittsburg, B.A. 2009 (Yeo Laboratory) Rajapogal, Nisha Indian Institute of Technology, B.A. 2007 (Ren Laboratory) Reis, Gerald Pomona College, B.A. 1997 (Goldstein Laboratory) Reyna, Sol Brown University, B.A. 2009 (Goldstein Laboratory) Rivera, Chloe University of California, Los Angeles, B.A. 2008 (Ren Laboratory) Rodrigues, Elizabeth University of Oregon, B.A. 2001 (Goldstein Laboratory) Ruff, Laura University of Minnesota, B.A. 2001 (Hedrick Laboratory) Rusert, Jessica Marie University of Wisconsin-Madison, B.A. 2002 (Goldstein Laboratory) Sclafani, Anthony University of Michigan, B.A. 2004 (Ferro-Novick Laboratory)

Graduate Students in CMM (continued) !

! ((!

Stanford, Kristen UCSD, B.A. 2009 (Esko Laboratory) Stark, Thomas James Emory University, B.A. 2008 (Yeo Laboratory) Su, Dan UCSD, B.A. 2009 (Hedrick Laboratory) Szpankowski, Lukasz University of Michigan- Ann Arbor, B.A. 2005 (Goldstein Laboratory)

Thacker, Bryan Edward University of Arizona, B.A. 2006 (Esko Laboratory) Tsau, Jennifer Northwestern University, B.A. 2009 (Hedrick Laboratory) Viscardi, Valeria University of Milan, B.A. 2000 (Oegema Laboratory) Wang, Shaohe Tsinghua University, B.A. 2008 (Oegema Laboratory)

Woodruff, Grace University of Washington, B.A. 2009 (Goldstein Laboratory) Welsh, Sarah Bryn Mawr, B.A. 2005 (Spector Laboratory) Wilbert, Melissa Louise Rochester Institute of Technology, B.A. 2008 (Yeo Laboratory) Zhang, Dawn Massachusetts Institute of Technology (Glass Laboratory)

!

!

Graduate Students who departed CMM in 2010 !Busch, Julia (Willert Laboratory) julia_busch@gmx.at Chow, Onh (Glass Laboratory) Current position: Medical Student Duke University de Albuquerque, Claudio Ponte (Zhou Laboratory) Current position: Postdoctoral Fellow UCSD cpontede@ucsd.edu Delgado Martin, Cristina (Farquhar Laboratory) Current position: Graduate Student CIB-CSIC, Madrid cdelgadomartin@yahoo.es Huang, Wendy Jia Men (Glass Laboratory) Current position: Postdoctoral Fellow NYU Wendy.Huang@med.nyu.edu

Kim, Yumi (Cleveland Laboratory) Current position: Damon Runyon Postdoctoral Fellow, University of California, Berkeley Kulukian, Anita (Cleveland Laboratory) Current position: Postdoctoral Fellow, Rockefeller University Lewellyn, Lindsay (Oegema Laboratory) Current position: Postdoctoral Fellow University of Chicago llewellyn@uchicago.edu !

Reis, Gerald (Goldstein Laboratory) Current position: Resident physician, Pathology, UCSF gerald.reis@ucsfmedctr.org Tang, Tingdong (Farquhar Laboratory) Current position: Postdoctoral Fellow UCSD tingdong@ucsd.edu

Taylor, Rachel E. (Varki Laboratory) Current position: Postdoctoral Scholar Stanford University Stanford, Kristen (Esko Laboratory) Current position: Research Fellow in Medicine Harvard University Medical School kristin.stanford@joslin.harvard.edu

The George E. Palade Celebration Symposium

January 28, 2010

The late Nobel Laureate George E. Palade, MD, Professor Emeritus of Medicine and Cellular and Molecular

Medicine, and founding Dean for Scientific Affairs at the University of California, San Diego School of Medicine, was

considered by his peers to be the father of modern cell biology. On January 28th, 2010 a day long symposium of

scientific lectures was arranged featuring speakers who work in areas he pioneered, worked with and knew George

Palade. The videos of these lectures are offered here to continue his spirit of scientific discovery and progress.

“Toward an Atomic Structure of the Nuclear Pore Complex”Gunter Blobel, MD, PhD

John D. Rockefeller, Jr. Professor, Investigator, HHMI, Laboratory of Cell Biology, Rockefeller University

Introduced by: Larry Gerace, PhD

“Many Faces of the Endoplasmic Reticulum”Peter Walter, PhD

Professor, Biochemistry and Biophysics, University of California, San Francisco

Introduced by: Jonathan Lin, MD, PhD

“Sorting Membrane Proteins at the trans-Golgi Network”Randy W. Schekman, PhD

Professor of Cell and Developmental Biology in the Department of Molecular and Cellular Biology, Investigator, HHMI, University of California at

Berkeley

Introduced by: Susan Ferro-Novick, PhD

“Sorting Out Membrane Traffic with Old Friends”Scott D. Emr, PhD

Director, Weill Institute for Cell and Molecular Biology, Frank H.T. Rhodes Professor, Department of Molecular Biology and Genetics, Cornell

University

Introduced by: Xiang-Dong Fu, PhD

“Molecular Basis of Eukaryotic Transcription”Roger D. Kornberg, PhD

Mrs. George A. Winzer Professor of Medicine, Department of Structural Biology, Stanford University

Introduced by: Chris Glass, MD, PhD

“Directing Membrane Traffic with Rab GTPase Regulatory Networks”Peter Novick, PhD

George E. Palade Professor, Department of Cellular and Molecular Medicine, UC San Diego

Introduced by: Marilyn Farquhar, PhD

“Nature’s Exquisite Nanomachines: The Myosin Family of Molecular Motors”James A. Spudich, PhD

Douglass M. and Nola Leishman Professor of Cardiovascular Disease, Departments of Biochemistry and Developmental Biology, Stanford

University School of Medicine

Introduced by: Larry Goldstein, PhD

“How Cells Control Cholesterol”Joseph L. Goldstein, MD

Regental Professor and Chairman, Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas

Introduced by: Dan Steinberg, MD, PhD

Click on any of the listed speakers to watch the video of their presentation

Pictures of the Symposium guests and attendees are available here

The original Symposium program and schedule is available here as a pdf document

!"#

Many of George Palade’s students and colleagues came from afar to attend the Symposium,

including:

•! Jim Jamieson, Yale University •! Lew Greene , University of Sao Paulo, Brazil •! Sam Silverstein, Columbia University •! Lily Bourguinon, University of California San Francisco •! Bill Brown, Cornell University •! Michael Caplan, Yale University •! Fred Gorelick, Yale University •! Kathryn Howell, University of Colorado •! Jack Kirsch, University of California Berkeley •! Jacopo Meldolesi, Vita-Salute San Ra!aele University in Milan, Italy •! David Sabatini, New York University Medical Center •! Jaakko Sarraste, University of Bergen, Norway •! Peter and Birgit Satir, Albert Einstein College of Medicine •! Alan Tartako!, Case Western University •! Pietro DeCamilli, Yale University

!$#

George Palade Symposium Photographs

Gunter Blobel, Marilyn Farquhar Peter Walter, Don Cleveland Jeff Esko, Joe Witzum Maho Niwa, Peter Walter

Suresh Subramani, Xiang-Dong Fu, Randy Schekman Peter Novick, Jim Jamieson Pietro DeCamilli, David Sabatini

Larry Goldstein, Suresh Subramani, Dan Steinberg Peter Novick, Connie Holm, Jeff Esko Xiang-Dong Fu, Scott Emr

Lucian Saucan, Radu Stan, Timo Meerloo, Marilyn

Farquhar, Dan and Sandra Predescu

David Sabatini, Sam Silverstein Larry Goldstein, Cynthia Grabow, Gordon Gill

Peter Novick, ? Kathryn Howell, Jim Jamieson

Larry Gerace, Don Cleveland, Peter Novick,

Sam Silverstein

Pietro DeCamilli, David Sabatini, Sandy Schmid,

Lou Green

Peter Novick, Fred Gorelick, Kathryn Howell, Jim Jamieson

!"#

CMM Faculty Dinner, June 2010