Contents · the social sciences, humanities, engineering, physical sciences, as well as the biomedical sciences. With ... Solarium 3:05pm Free Time -Guided tour with Jim Hall

1

Medical Scholars Program

College of Medicine at Urbana-Champaign

2015 Annual Retreat

Contents

Director’s Welcome 2

About the Medical Scholars Program 2

Schedule of Events 3

MSP Entering Class of 2015 4

Acknowledgements 5

Outstanding Advisor Award 6

Keynote Speaker Information 7

Past Keynotes 8

Alumni Speakers 10

CME Credit Offering 12

Student Speaker Biographies and Abstracts 13

Description of Breakout Sessions 19

Poster Abstracts 20

2

Director’s Welcome



2015 Annual Retreat

The Medical Scholars Program (MSP) first admitted students in 1978. A few

short years later, in 1981, we held the first MSP Retreat. As the program

grew, so too did the retreat, and in the mid-80’s the retreat found its home at

Allerton Park and Retreat Center.

In celebration of the 35th Annual MSP Retreat, and in honor of the Medical

Scholars Program and its 360 alumni and 109 current students, we are

pleased to welcome back: Alex and Erik Adams, Erik Antonsen, Gordon Bu-

chanan, Jackie Payton, Richard Perrin, Ed Plowey, Todd Purves, Hanna Ste-

vens, and Michael Wilson.

I want to thank the members of the MSP Annual Retreat Planning Commit-

tee, co-chaired by Jenn Hou and Alex Cerjanic, as well as Debbie Deedrich,

Chantelle Thompson and Heather Wright for all of their hard work. I would

also like to thank all those who contributed financially for this special occa-

sion.

Enjoy yourselves!

Jim Slauch, PhD, Director of the Medical Scholars Program

About the Medical Scholars Program

The MSP is committed to preparing a diverse cadre of physician-scholars to confront the multi-dimensional

problems and issues that face medicine. The complex nature of these problems requires people trained in a

broad array of graduate disciplines working together in order to develop innovative solutions. The MSP has

over 100 MD/PhD and MD/JD students pursuing graduate study in over 30 academic disciplines, including

the social sciences, humanities, engineering, physical sciences, as well as the biomedical sciences. With

such diverse student perspectives, the MSP provides a unique and electric environment for bright and crea-

tive scholars to pursue their passion for combining cutting edge research with individualized high quality clini-

cal training.

Our annual retreat, now in its 35th year, has not significantly changed since its inception. Originally held at

the Illini Union, this conference began with the objective of bringing the MSP community of students, staff and

faculty together to share ideas and insights, and most of all to have fun. Past retreat organizers have chosen

to honor administrators such as Hal Swartz and Tony Waldrop with “roast” videos or slide shows. While each

year’s retreat has it own personality, the guiding purpose of hosting an MSP “community of ideas” has re-

mained a steadfast tradition.

3



2015 Annual Retreat

Time Event Location

9:30am Check-in Lobby

10:00am Welcome and Opening Remarks -Advisor of the Year

Library

10:30am Morning Student Talks -Gregory Damhorst -Morgan Moon -Elise Duwe

Library

11:15am Morning Breakout Session -MSP Students in the Humanities -Ask the Jims (Jim Slauch and Jim Hall) -What I Wish I Knew: Advice on the transition to M2

Oak Room Butternut Room Pine Room

12:00pm Lunch Dining Room

1:00pm Alumni Panel -Dr. Erik Adams -Dr. Edward D. Plowey -Dr. J. Todd Purves -Dr. Michael Wilson

Library

1:30pm Afternoon Student Talks -Jake Carpenter-Thompson -Samantha Pisani -Molly Melhem

Library

2:15pm Afternoon Breakout Session -Dr. David Hyman (CME credit available) -MSP Community Development

Library Solarium

3:05pm Free Time -Guided tour with Jim Hall -Lawn games

5:00pm Poster Session and Cocktail Hour Solarium

6:00pm Dinner Dining Room

7:00pm Keynote Address -Dr. Alex Adams, MD, PhD

Library

8:00pm Concluding Remarks Library

8:30pm Evening Activities

Schedule of Events

4

MSP Entering Class of 2015



2015 Annual Retreat

Kelly Hewes

Neuroscience

Name Graduate Program

Undergraduate Institution Undergraduate Major

Kelly Hewes

Trinity University Neuroscience, (Minor: Chemis-try)

Lucy Mailing

Kalamazoo College Biology (with concentration in Neuroscience), (Minor: Psychol-ogy)

Lawrence Wang

California Institute of Technology Biology

Lucy Mailing

Nutritional Sciences

Lawrence Wang

Molecular & Cellular

Biology

5



2015 Annual Retreat

Acknowledgements

MSP & Student Affairs Administration

Michele Mariscalco, MD

Dean

College of Medicine

James Slauch, PhD

Director

MSP

James Hall, EdD

Associate Dean

SA & MSP

Nora Few, PhD, RD

Executive Assistant

Dean SA & MSP

Heather Wright, MS

Coordinator

SA & MSP

Julie Wyant

Office Manager

SA & MSP

Tenacia Gardner

Office Support Specialist

SA, MSP & UHP

Retreat Planning Committee

Alex Cerjanic (co-chair), Hanna Erickson, Luke Fenlon, Daniel Harris, Sarah Holton,

Jenn Hou (co-chair), Kerim Kaylan, Ted Kim, Chris Liu, Katie Magerko, Aidas Mattis,

Mike Tencati, and Emily Tillmaand.

6



2015 Annual Retreat

Outstanding Advisor Award The role of an MSP advisor brings with it many unexpected challenges. MSP students must balance their graduate and

medical pursuits and MSP advisors often put in extra effort to understand and guide their students through this lengthy

and often stressful process.

In 2000, through an effort to spotlight the significance and continued high quality of faculty mentoring, the MSP Advisory

Committee awarded the first MSPAC Outstanding Advisor Awards. Each year since, MSPAC had called for nomination

letters and, at the MSP Annual Retreat, recognized those faculty mentors whose contributions to our graduate and medi-

cal education have been exemplary.

Recipients’ names are displayed on a plaque in the MSP office so that future students will recognize the outstanding re-

source provided to us by our mentors. Copies of the written nomination statements are on file in the MSP office.

MSPAC wishes to thank everyone who participated in this year’s Outstanding Advisor Award search, and encourage all

interested MSP students to nominate their advisors in coming years.

2015 Outstanding Advisor Award

Lori T. Raetzman, PhD Molecular and Integrative Physiology

To say that Lori Raetzman is the best advisor for an as-piring MD/PhD may be the understatement of the centu-ry.

Rather than treating the lab as a singular unit and treat-ing us as drones to manufacture data like an assembly line, she takes the time to learn about what we are inter-ested in, how to personally motivate each of us, and what projects to hand out to ensure that we are not only extraordinarily productive, but also all thoroughly enjoy what we do every day we show up to lab. I can whole-heartedly say that deep down, I know that everything Lori has assigned or suggested I do is to ensure that I am the most prepared I can possibly be when I move to the next step of my life.

-Matthew Biehl

Nominated by Matthew Biehl

James M. Slauch, PhD Microbiology

Jim is an outstanding research advisor who is always excit-ed to discuss our projects and provide insightful guidance. For that alone he is worthy of this nomination. On top of that he is extremely dedicated to educating future scientists and physicians, teaching courses to both undergraduates and medical students. Finally, in the role most of you rec-ognize him, he is director of the MSP. We can personally vouch for his dedication to all students finding success within the program.

-Luke Fenlon and Koh Eun Narm

Nominated by Luke Fenlon and Koh Eun Narm

7



2015 Annual Retreat

Previous MSPAC Outstanding Advisor Award Winners

Year Awardee(s) College(s), Department(s) or Division(s)

2014 David Kranz, PhD James Morrissey, PhD

Biochemistry Biochemistry

2013 Justin Rhodes, PhD Sua Myong, PhD

Psychology, Nutritional Science Bioengineering

2012 Stephanie Ceman, PhD Claudio Grossman, PhD

Cell & Developmental Biology Molecular & Integrative Physiology

2011 Philip Best, PhD Molecular & Integrative Physiology, Neuroscience, Biophysics, Bioengineering

2010 Brian Cunningham, PhD Electrical & Computer Engineering, Bioengineering

2009 Mark Micale, PhD Leslie Reagan, PhD

History History

2008 Richard Tapping, PhD Microbiology

2007 Edward Roy, PhD Molecular & Integrative Physiology, Pathology, Neuroscience

2006 Reginald Alston, PhD Community Health

2005 Richard Gumport, PhD Enrico Gratton, PhD

Biochemistry Physics

2004 Harris Lewin, PhD Ruth Watkins, PhD

Animal Science Speech & Hearing Science

2003 Roberto DoCampo, PhD Bruce Wheeler, PhD

Veterinary Pathobiology Electrical & Computer Engineering

2002 Martha Gillette, PhD Janet Reis, PhD

Cell & Structural Biology Community Health

2001 Janice Bahr, PhD John Katzenellenbogen, PhD Bruno Nettl, PhD Robert Rich, PhD

Molecular & Integrative Physiology Chemistry School of Music College of Law

2000 David Kuehn, PhD Stephen Sligar, PhD Paula Treichler, PhD

Speech & Hearing Science Biochemistry Institute of Communications Research

8



2015 Annual Retreat

About the Keynote Speaker

Alexandra Adams, MD, PhD

Dr. Alexandra Adams is a Professor in the Department of Family Medicine, University of Wisconsin School of Medicine and Public Health. As Director of the UW Collaborative Center for Health Equity, a center that focuses on enhancing health equity across underserved Wisconsin communities, Dr. Adams is in a strong position to provide expertise on collaborative community partnerships, health equity, and community based research in underserved populations. She is currently practicing at The UW Health Pediatric Fitness Clinic. Her special interests include pediatric nutritional problems, obesi-ty, metabolic syndrome and indigenous diets and health. Dr. Adams places a special emphasis on working in partnership with families and children to help them make healthier lifestyle choices.

Dr. Adams and her research team have been working in collaboration with tribal communities for the past 15 years on NIH supported research focused on the prevention of pediatric obesity and related chronic disease through healthy lifestyle interventions. Currently, Dr. Adams leads a family-based intervention project - Healthy Children, Strong Families to reduce obesity and cardiac risk factors in American Indian children in 5 states. This participatory research project is a NIH funded randomized controlled trial examining the effect of a family based intervention to reduce metabolic risk and im-prove healthy lifestyles in the children and their primary caregivers.

Dr. Adams’ presentation is titled From the Flatland to the Tall Pines: My Journey Towards Commu-nity Research Partnerships to Improve Health in American Indian Communities. Her talk will focus on her scientific biography, and how she went from basic science research to community based re-search with American Indian communities. She will also share her insight and understanding of the journey towards a successful career in academic medicine.

9



2015 Annual Retreat

Past Keynotes

(*denotes alumnus)

2014 Gordon Buchanan, MD, PhD*

Hanna Stevens, MD, PhD*

Assistant Professor, Neurology, University of Iowa College of Medicine

Assistant Professor, Psychiatry, University of Iowa College of Medicine

2013 Martin Pomper, MD, PhD* Professor, Neuroradiology Division, Johns Hopkins University

2012 Charles Hardin, MD, PhD* Instructor in Medicine, Harvard Medical School; Staff Physician, Mass General

2011 Michael Milhan, MD, PhD* Associate Director, Pediatric Neuroscience, NYU Child Study Center; Assistant Professor, NYU

2010 Annette Schlueter, MD, PhD* Associate Professor, Pathology, Univ of IA; Lab Medical Director, DeGowin Blood Center

2009 Keith Cengel, MD, PhD* Assistant Professor, Radiation Oncology, University of Pennsylvania

2008 Scott Selco, MD, PhD* Medical Director of Stroke Care, Sunrise Hospital Stroke Center

2007 John Chen, MD, PhD Attending Radiologist, Neuroradiology, Massachusetts General Hospital

2006 Jaime Feldman, MD, PhD* Assistant Professor, Family Medicine and Community Health, University of MN

2005 Nora Zorich, MD, PhD* Vice President, Global Drug Development, Procter and Gamble Pharmaceuticals

2004 M. Kerry O’Banion, MD, PhD* Associate Professor, Neurology, University of Rochester; Director of MSTP

2003 Martin Pomper, MD, PhD* Associate Professor, Radiology, Johns Hopkins; Director, Small Animal Imaging

2002 James Shoemaker, MD, PhD* Assistant Professor, Biochemistry and Molecular Biology, St. Louis University

2001 Raynard Kington, MD, PhD Associate Director, Behavioral & Social Sciences Research, NIH

2000 James Wilson, MD, PhD Director, Institute for Human Gene Therapy; Professor, University of Pennsylvania

1999 Eric Wong, MD, PhD Associate Professor, Radiology and Psychiatry, University of California San Diego

1998 Rolf Gunther, MD, PhD Vice President, Clinical Research and Development, Centeon

1997 David Trawick, MD, PhD* Assistant Professor, Pulmonary and Critical Care, University of Rochester

1996 F. Andrew Gaffney, MD Associate Director, Space Physiology; Chief, Clinical Cardiology; Prof. Vanderbilt

1995 Joseph Davie, MD, PhD Vice President, Research, Biogen Inc; Adj Prof, Microbiology, Washington U.

1994 M. Kerry O’Banion, MD, PhD* Associate Professor, Neurology, University of Rochester; Director of MSTP

1993 Thomas Huddle, MD, PhD* Assistant Professor, General and Preventative Medicine, Univ. of Alabama

1992 Cutberto Garza, MD, PhD Director, Nutritional Science, Cornell University

1991 Steven Wartman, MD, PhD Director, Internal Medicine; Professor, Brown University

1990 Samuel Their, PhD President, Institute of Medicine, National Academy of Sciences

1989 DeWitt Baldwin, MD Director, Division of Medical Education, American Medical Association

1988 Donald Bord, MD Senior Scientist, Brookhaven National Laboratory

1987 Samuel Shem, MD, PhD Psychiatrist; Instructor, Harvard Medical School

1986 Timothy Baker, MD, MPH Professor, Johns Hopkins University; Visiting Professor University of Indonesia

10



2015 Annual Retreat

About the Alumni Panelists

Erik Adams graduated from the Medical Scholars program in 1994 with

an MD and a PhD in Chemistry. His graduate work investigated biosyn-

thesis of antibiotics by microbes. He completed a residency in pediatrics

at the University of Wisconsin and then worked for a year as an ER phy-

sician in southern Wisconsin. This was followed by a fellowship in non-

operative Sports Medicine at Maine Medical Center in Portland,

Maine. For the past 14 years, Dr. Adams has had a solo sports medicine

practice in Madison, Wisconsin. He has also been an instructor and lec-

turer in musculoskeletal ultrasound courses for the American Medical So-

ciety for Sports Medicine and the American College of Sports Medi-

cine. Erik is married to Alexandra Adams, who is also an MSP alum, and

they have three children.

Erik Adams, MD, PhD

Ed Plowey, MD, PhD

Edward D. Plowey completed his BS in Neuroscience at the University of Pittsburgh in

1996. He subsequently joined the Medical Scholars Program at the University of Illinois

at Urbana-Champaign. He completed his PhD studies in Molecular and Integrative Phys-

iology in 2004 during which he analyzed the central neural control of breathing during

exercise under the guidance of Tony G. Waldrop, PhD Subsequently, Dr. Plowey com-

pleted his MD in 2005. He then trained in Anatomic Pathology and Neuropathology, with

integrated postdoctoral research training in the Pathologist Investigator Research Resi-

dency Training Program, at the University of Pittsburgh under the guidance of Charleen

T. Chu, MD, PhD. In 2012, Dr. Plowey was appointed Assistant Professor of Pathology

at Stanford University School of Medicine. He focuses 75% of his effort on his laboratory

research, 15% on dementia autopsy neuropathology research for the Stanford Alzheimer

Disease Research Center and 10% on surgical neuropathology and ophthalmic patholo-

gy.

Dr. Plowey’s laboratory research is focused on mechanisms of neurodegeneration and how neurons eliminate or mitigate

stressors. The laboratory primarily focuses on neuronal regulation of autophagy and endolysosomal degradation. His work

has elucidated an important autophagy master regulatory transcription factor and forthcoming new insights into the regula-

tion of amyloid precursor protein degradative sorting by autophagy/endolysosomal regulatory proteins. His research is sup-

ported by a K08 grant from the NIH/NINDS and a New Investigator in Alzheimer Disease Award from the American Federa-

tion for Aging Research (AFAR). Dr. Plowey is also the Director of the Stanford Health Care Brain Bank, co-Director of the

Neuropathology and Biospecimens Core of the NIA-funded Stanford Alzheimer Disease Research Center and autopsy Neu-

ropathologist for the Stanford Brain Rejuvenation Project.

11



2015 Annual Retreat

About the Alumni Panelists

J Todd Purves, MD, PhD

J Todd Purves earned his BA in Chemistry at Cornell University in 1991. He pursued an

MD/PhD at The University of Illinois in Urbana-Champaign, completing his PhD in Bio-

chemistry in 1998 and MD subsequently in 2000. Dr. Purves conducted research as a

visiting scientist at The Max Planck Institute for Polymer Research in Mainz, Germany in

1994. Following, he completed his General Surgery residency and Urology residency at

The University of Arizona, and Pediatric Urology Fellowship at The Johns Hopkins Hos-

pital. Dr. Purves was an Associate Professor of Urology, Pediatrics and Regenerative

Medicine and Cell Biology at The Medical University of South Carolina and has recently

joined The Duke Urology Faculty in July 2015.

While at The Medical University of South Carolina, Dr. Purves and his colleague Dr.

Monty Hughes co-founded the Basic Urology Research Laboratory at MUSC in 2010.

They first demonstrated that inflammasome forming Nod like receptors in the urothelium

play a role in sterile cystitis. This research has led to a new understanding of bladder deterioration in cases of blad-

der outlet obstruction. In addition, Dr. Purves has contributed to the development of the first interactive three dimen-

sional map of human bladder innervation. This map will enable the advancement of ablative therapies for overactive

bladder and enable nerve sparing surgical procedures.

Dr. Wilson is an attending physician at the University of Califor-nia San Diego Department of Emergency Medicine. He is a proud Midwesterner, having obtained both a PhD in cognitive neuroscience and a medical degree at the University of Illinois. He completed his fellowship in clinical research in 2012 at UCSD, and currently serves as the Director of Emergency Psy-chiatry Research for the American Association for Emergency Psychiatry, the Medical Director of Aeromedevac Air Ambulance based in San Diego, the Associate Director of the UCSD De-partment of Emergency Medicine Clinical Research Scholar fel-lowship, and the Director of the UCSD Department of Emergen-cy Medicine Behavioral Emergencies Research (DEMBER) lab. The DEMBER lab’s research primarily focuses on applied psy-chiatric emergencies of clinical relevance to emergency physi-cians, with recent projects on suicide screening, agitation, and the side effects of second generation antipsychotics in an ED setting. He is a section editor and reviewer for several academic journals and is published broadly in the field of behavioral emergencies and agita-tion.

Michael Wilson, MD, PhD

12



2015 Annual Retreat

CME Credit Offering:

The Affordable Care Act

David A. Hyman, MD, JD, is the H. Ross and Helen Workman Chair in Law and Professor of Medi-

cine at the University of Illinois, where he directs the Epstein Program in Health Law and Poli-

cy. He focuses his research and writing on the regulation and financing of health care, and on em-

pirical law and economics. He teaches or has taught health care regulation, civil procedure, insur-

ance, medical malpractice, law & economics, professional responsibility, and tax policy.

While serving as Special Counsel to the Federal Trade Commission, Professor Hyman was princi-

pal author and project leader for the first joint report ever issued by the Federal Trade

Commission and Department of Justice, “Improving Health Care: A Dose of Competition”

(2004). He is also the author of “Medicare Meets Mephistopheles,” which was selected by the U.S.

Chamber of Commerce/National Chamber Foundation as one of the top ten books of 2007. He has

published widely in student edited law reviews and peer reviewed medical, health policy, law, and

economics journals.

David Hyman, MD, JD

13



2015 Annual Retreat

Student Speaker Biographies and Abstracts

Jake Carpenter-Thompson

Jake Carpenter-Thompson recently earned a PhD in Neuroscience. His work focused on the develop-

ment of novel treatment options for those that suffer with tinnitus, ringing in the ears. To complete his dis-

sertation research, he won a highly competitive grant from the American Tinnitus Association. After the

completion of his MD, he plans to conduct cutting edge, patient centered research to improve the quality

of life of those he serves in the community.

Title: Can Physical Activity Alleviate Ringing in the Ears?

Authors: Jake Carpenter-Thompson, Sara Schmidt, Edward McAuley, Fatima T. Husain

Abstract: The main problem facing individuals with tinnitus is not the sound itself rather it is the negative

emotional reaction to the sound that may result in increased anxiety and depression. Physical activity

has been correlated with lower levels of anxiety and depression, but, this has not been established in the

tinnitus population. Therefore, we investigated the association between physical activity and tinnitus dis-

tress.

14



2015 Annual Retreat

Gregory Damhorst

Greg Damhorst holds a BS in physics and MS in bioengineering from the University of Illinois at Urbana-

Champaign. He is interested in clinical applications of point-of-care diagnostic technologies that enable

measurements not previously possible. He was a co-founder of the Global Health Initiative in 2011 which has

sought to build an interdisciplinary community on the Urbana campus around global health. Greg and his wife

Lacie, a registered nurse and a Quality Outcomes Coordinator at Carle, were married in 2014.

Title: Point-of-care diagnostic technologies for HIV/AIDS applications

Authors: Gregory Damhorst, Umer Hassan, Carlos Duarte-Guevara, Weili Chen, Tanmay Ghonge, Brian

Cunningham, Rashid Bashir

Abstract: Human Immunodeficiency Virus (HIV) has been responsible for the deaths of more than 34 million

people to date, while 36.9 million people worldwide live with the infection today. Antiretroviral therapy (ART),

which first emerged in the late 1980s, has made it possible to live with HIV as a chronic disease with minimal

effect on life expectancy. However, significant barriers remain to bringing the standard of care to millions of

HIV-positive individuals, particularly in remote and resource-limited settings. Among these barriers is the lim-

ited availability of the appropriate diagnostic technologies for monitoring the core markers of treatment effica-

cy: the CD4+ T lymphocyte count and blood plasma viral load. We have applied micro- and nanotechnology

solutions to develop platforms which could enable portable, low-cost, user-friendly, point-of-care diagnostics

for HIV/AIDS applications. Our CD4 counting platform employs microfluidic handling of small volumes of

whole blood, impedance biosensor technology, and immunoaffinity cell capture to enumerate CD4 T cells on

a chip the size of a credit card. Meanwhile, we have implemented reverse-transcription loop-mediated iso-

thermal amplification (RT-LAMP) in microchip formats for virus detection in minimally-processed whole blood

samples with consumer smartphone detection.

15



2015 Annual Retreat

Elise Duwe

Elise is in the MSP and Department of Sociology. Elise graduated from College of Wooster in Biochemistry

and Religious Studies. During 2013-2015 she held an INTERSECT fellowship from American Indian Studies.

She was a Visiting Scholar at the Robert Graham Center for Policy Studies in Primary Care. She has publica-

tions in Health Education Journal and American Family Physician and has presented at global conferences:

3rd Global Congress for Qualitative Health Research, North American Primary Care Research Group Annual

Meeting, and International Congress of Qualitative Inquiry. On campus, she volunteers with Education Justice

Project, Daily Bread Soup Kitchen, Walking School Bus, and Hermes Clinic.

Title: Like a Broken Toy: The Social, Psychological, and Cultural Impacts for American Indians Suffering from

Chronic Pain

Author: Elise A.G. Duwe

Abstract: This talk will explore the difficult conversations and places of tension in the experience of chronic

pain for American Indians who live off-reservation. American Indian chronic pain sufferers struggle with the

multiplicative invisibility of both their chronic pain condition and their native identity. The invisibility leads to

passing as white in environments hostile to people of color. It also results in family disconnection, loneliness,

and isolation. In order to survive these socially-mediated assaults, American Indian chronic pain sufferers

keep their psyche at peace through stress management, cultural engagement, and non-negativity. A warrior

strength from understanding that American Indians as peoples have always survived bolsters individual

strength to push through the pain and keep on living. This research provides insight into the social, psycho-

logical, and cultural impacts of suffering from chronic pain.

16



2015 Annual Retreat

Molly Melhem

Molly’s journey began in 1985, in the great town of bridges and steel known colloquially as Pittsburgh Penn-

sylvania. It was here that she learned the art of cheering for a winning football team, something that would not

prove to be a useful skill after coming to the U of I. From Pittsburgh, Molly bee bopped over to Ithaca NY, fol-

lowed by a two year stint at the Dana Farber Cancer Institute in Boston, and finally landed in the flat but glori-

ous hippy mecca of Urbana IL to spend eight long, blissful years pursuing her dual degree in bioengineering

and medicine.

Title: A Cardiac Patch for Delivering Therapeutic Stem Cells to the Heart Following Myocardial Infarction

Authors: Molly Melhem, Tor Jensen, Luke Knapp, Larissa Reinkensmeyer, Min Kyung Lee, Jae Hyun Jeong,

Vincent Chan, Caroline Cvetkovic, Rashid Bashir, Hyunjoon Kong, Lawrence Schook

Abstract: While medical practices to address the immediate aftermath of a myocardial infarction (MI) have

evolved tremendously, there are no techniques currently administered to slow, cease, or reverse the negative

side effects of an occluded artery. The marginal ability of cardiomyocytes to divide and repopulate the infarct-

ed area results in the replacement of functional myocardium with non-contractile scar tissue. As a result, the

burden of heart function lies on the surrounding tissue; a load that exhausts the healthy tissue and decreases

the quality of life of heart attack survivors. Mesenchymal stem cells have emerged as a promising therapeutic

avenue for post-MI treatment, in part due to the “survival signals” that they secrete. Previous work has shown

increasing the amount of “survival signals” that are introduced to the damaged myocardium can decrease

cardiomyocyte cell death and subsequent scar formation. While the therapeutic effects of these factors have

been documented, the difficulty lies in maintaining a constant flux of secreted factors to the damaged site.

This project hypothesizes that through the encapsulation of stem cells within an engineered hydrogel con-

struct, the hurdle of soluble factor delivery at the site of injury can be overcome to improve cardiac function

following a heart attack.

17



2015 Annual Retreat

Morgan Moon

Morgan is a MS-3 in her 8th year of the MSP. She successfully completed her PhD in August of 2014 in the

laboratory of Dr. Gregory Freund. In her spare time she enjoys relaxing days with her husband and partner

of 12 years, their toddler, and their small herd of cats and dogs. When not on the wards or studying, she

can often be found on a bicycle, running, or exercising creative release in the kitchen.

Title: Scared stupid: A tale of serendipitous discovery

Authors: Morgan Moon, Jennifer Joesting, Neil Blevins, Marcus Lawson, Stephen Gainey, Albert Towers,

Leslie McNeil, Gregory Freund

Abstract: Inflammation is a recognized antecedent and coincident factor when examining the biology of anx-

iety. Little is known, however, about how reductions in endogenous anti-inflammatory mediators impact anx-

iety. Therefore, mood- cognition- and anxiety-associated/like behaviors were examined in IL-4 knock out

(KO) mice and wild-type (WT) mice. In comparison to WT mice, IL-4 KO mice demonstrated decreased bur-

rowing and increased social exploration. No differences were seen in forced swim or saccharine preference

testing. IL-4 KO mice had similar performance to WT mice in the Morris water maze and during object loca-

tion and novel object recognition. In the elevated zero-maze, IL-4 KO mice, in comparison to WT mice,

demonstrated anxiety-like behavior. Anxiety-like behavior in IL-4 KO mice was not observed, however, dur-

ing open-field testing. Taken together, these data indicate that IL-4 KO mice display state, but not trait, anxi-

ety suggesting that reductions in endogenous anti-inflammatory bioactives can engender subtypes of anxie-

ty.

18



2015 Annual Retreat

Samantha Pisani

Samantha Pisani recently received her PhD in Neuroscience from UIUC this past May. She completed under-

graduate training at the University of San Diego, receiving a BA in Biology with honors. As an undergrad,

Sam completed research experiences at the Claremont Colleges and Scripps Research Institute. Following

graduation, she conducted research in the Vale Neuroendocrinology Lab at the Salk Institute. It was there

that she fell in love with neuroscience and decided to pursue dual-degree training through the MSP. In addi-

tion to science and medicine, Sam’s passions include her husband Matt, her two rambunctious dogs, cook-

ing, and dance.

Title: Estrogenic modulation of place and response learning via specific receptor-mediated mechanisms

Abstract Authors: Samantha L. Pisani, Donna L. Korol

Abstract: Estrogens are best known for their roles in reproductive behavior and physiology, but they also con-

tribute substantially to normal brain function. The effects of estrogens on brain and cognitive health are partic-

ularly important because should they live long enough, all women will undergo a dramatic loss of estrogen

and progesterone through menopause. This work examines the contributions of estrogen receptor (ER) sub-

types to shifts in learning and memory in ovariectomized female rats. Our results reveal that treatment with

agonists selective for ERα, ERβ, or GPER were all sufficient to enhance place learning and impair response

learning. These findings emphasize that multiple receptor-mediated pathways contribute to estrogenic shifts

in cognition, and that independent activation of a single receptor appears sufficient to induce these mnemonic

changes. Results from quantitative Western blot analyses show that patterns of estrogen-regulated ERK acti-

vation in the hi ppocampi and striata are nuanced, varying according to learning task performance and the ER

subtype targeted. Together, the findings of these studies elucidate some of the neurobiological mechanisms

that underlie estrogen-induced shifts in learning and memory and may have implications for the development

of new treatments aimed at preserving cognitive function over the lifespan.

19



2015 Annual Retreat

Description of Breakout Sessions

MSP Humanities Discussion

Oak Room

The Medical Scholars Program at the University of Illinois Urbana-Champaign is one of the eleven MD/PhD

programs in the country to offer fields of study in the Medical Humanities and Social Sciences (MHSS). It al-

so happens to be among the largest of such programs. Students studying or interested in fields such as soci-

ology, history, anthropology, philosophy, comparative literature, economics, law, communications, business,

community health, and human and community development are invited to discuss ideas for events and future

directions of the MHSS student group.

Ask the Jims

Butternut Room

Have any questions about the MSP? Want answers as to how funding works for MSP students? Curious as

to the past, present and future of the MSP? Attend this breakout and get your answers straight from Jim Hall

and Jim Slauch.

What I Wish I Knew: Advice on the Transition from M1 to M2

Pine Room

Part 1: USMLE Step 1 Preparation

Are you starting M2 this fall? Are you an M1 or pre-M1 that wants to know how M1 classes can help you pre-

pare for Step 1? This breakout session will cover how to prepare for the exam, what study resources are

available to aid your preparation, and to address any other questions about the USMLE Step 1. This is the

most important test we take as medical students. Residency programs use these scores as major criteria in

sorting and ranking applicants.

Part 2: M3/M4 Panel Discussion Join us for a moderated panel discussion with M3 and M4 students as they share their experiences on transi-

tioning. Come get your questions answered and enjoy interacting with your fellow MSP students!

CME: The Affordable Care Act

Library

Students and alumni are invited to attend this CME session. Dr. David Hyman will be presenting, and the fo-

cus of his talk will be the Affordable Care Act.

MSP Community Development

Meet in the Solarium

Meet your fellow MSP classmates during teambuilding activities including speed networking and lawn

games! Activity leaders will station themselves in the Solarium to organize groups of students for each team-

building activity. This is an excellent opportunity to meet new and not-so-new students.

20



2015 Annual Retreat

Poster Abstracts

Characterizing Membrane-bound Factor X Using Molecular Dynamics

Melanie Muller

Factor X (FX) is an enzyme important to initiating the blood coagulation cascade. In order to promote blood

clotting, FX’s calcium-rich γ-carboxyglutamic acid (gla) domain must bind to a cell’s plasma membrane. Is has

been shown that the FX gla domain preferentially binds membranes rich in phosphatidylserine (PS), but the

molecular basis of the affinity is unknown. There is also currently no structural information available for the

membrane bound state of FX at the atomic level. In order to characterize the binding, orientation, and lipid

interactions of the factor X gla domain, a molecular dynamics approach has been employed. Using a novel

membrane representation, highly mobile membrane mimetic (HMMM), which displays enhanced lipid mobility

and dynamics, the insertion of the gla domain ω-loop into the membrane has been captured and the mem-

brane-bound gla domain structure characterized. The structure provides insight into possible causes of the

PS specificity of the Factor X gla domain.

Endothelin Receptor Antagonism in Single Ventricle Physiology with Fontan Palliation: A Systematic

Review and Meta-analysis

Gwendolyn Derk, BS, Ruopeng An, PhD, Jamil Aboulhosn, MD

This study systematically reviewed existing evidence and performed a meta-analysis to determine the safety

and efficacy of endothelin receptor antagonism in single ventricle physiology with Fontan palliation. Methods:

Keyword and reference search was conducted in PubMed, Cochrane Library, Web of Science, Google Schol-

ar, and ClinicalTrials.gov databases. Inclusion criteria were – study design: randomized controlled trials, co-

hort studies, prospective studies, or retrospective studies; subjects: single ventricle patients with Fontan palli-

ation; main outcome: exercise or functional capacity; and article type: peer-reviewed publications. Results:

Five studies met the inclusion criteria, including three pre-post studies, one randomized crossover open label

clinical trial, and one double-blind randomized controlled clinical trial. Study durations ranged from 3.5 to 6

months, with a total sample size of 123. No significant increase in liver toxicity or other serious adverse event

was reported in these studies. Meta-analysis found bosentan use to be associated with improvement in func-

tional class (p = 0.0007); whereas no significant change in six-minute walk distance, resting oxygen satura-

tion, and maximal oxygen consumption was identified. Conclusions: Bosentan was found to be a safe and

well tolerated endothelin receptor antagonist in Fontan patients over 3-6 months of therapy. Bosentan use

was associated with improved functional capacity.

Role of Scaffolding Protein IQGAP1 in Fat Metabolism

Hanna Erickson, Karen Wendt, Sayeepriyadarshini Anakk

IQGAP1 (IQ motif-containing GTPase Activating Protein 1) is a ubiquitously expressed protein that integrates

signaling from numerous cellular processes. Recently, it has been identified as a scaffold for MTORC1 signal-

ing uncovering its role in regulating metabolism. In the fed state, the liver regulates energy balance by pro-

moting glycogenesis and fatty acid synthesis while inhibiting gluconeogenesis. Contrarily, we observed that

fed Iqgap1-/- mice exhibit decreased hepatic fatty acid synthase expression and elevated fructose 1,6-

bisphosphatase expression indicating reduced fatty acid synthesis and increased gluconeogenesis,

21



2015 Annual Retreat

respectively. Furthermore, fed Iqgap1-/- mice displayed lower serum triglyceride levels suggesting dysregula-

tion of lipid metabolism. We then examined WT and Iqgap1-/- mice both under fed and 24-hour fasted condi-

tions. As expected, fasting decreased body weight, ratio of liver to body weight, and serum triglycerides in

both sets of mice. Furthermore, prolonged fasting normally induces β-oxidation of fatty acids. However, we

found blunted induction of β-oxidation genes in Iqgap1-/- mice. FGF21 is a major mediator of the fasting re-

sponse and regulates these genes. Therefore, we checked Fgf21 expression and found that its induction in

Iqgap1-/- mice was severely reduced. Our findings reveal that IQGAP1 is crucial to promote the fasting-

induced FGF21 response and its loss alters lipid metabolism.

A Genetic Risk Score Demonstrates the Cumulative Association of SNP in Gut Microbiota Related

Genes with Obesity Phenotypes in Preschool Age Children

Anthony Wang, Kristen Harrison, Sharon M. Donovan, Margarita Teran-Garcia, and the STRONG Kids

Research Group

Childhood obesity is a nutrition-related disease with multiple underlying etiologies. While genetic factors con-

tribute to obesity, the gut microbiota has been implicated through fermentation of non-digestible polysaccha-

rides to short chain fatty acids (SCFA). SCFA provide additional substrate for energy harvest and storage,

and are postulated to be signaling molecules effecting expression of gut hormones. Methods: This study in-

vestigated the cumulative association of single nucleotide polymorphisms (SNP) of genes involved in SCFA

recognition and metabolism with obesity. Study participants were non-Hispanic White children (2-5 yrs.) from

the STRONG Kids Illinois and Michigan cohorts (n=270). Height and weight were measured to calculate obe-

sity-related phenotypes. Genomic DNA was extracted from saliva and genotyped using the Fluidigm® plat-

form. Statistical analyses were performed in SAS 9.4. Ten SNP variables (PPARG, ANGPTL3/4, LPL, PYY,

NPY2R, SLC5A8, SLC16A3, SLC16A1, and IL6) were dichotomized according to dominant or recessive in-

heritance models with the effect size of each SNP variable on BMI Z-score established using β-estimates

from general linear models. A weighted genetic risk score (GRS) was generated by summing the ten β-

estimates. Results: The GRS was significantly associated with BMI Z-score with the model explaining 12.4%

of the variance using linear regression (r2=0.124, p<0.0001). Similarly, the GRS was associated with weight-

for-age Z-score but not with height-for-age Z-score (r2=0.045, p=0.002). Conclusion: This preliminary analy-

sis suggests the cumulative association of the genetic variants studied with early-onset obesity. Our data

supports the concept that gut microbiota influences obesity development through key host genes interacting

with SCFA, warranting further investigation into the mechanisms driving these associations.

Identifying Novel Factors Involved in Salmonella Typhimurium Defense Against Phagocytic

Superoxide using Differential Tn-Seq

Luke Fenlon, James Slauch, PhD

Nontyphoidal Salmonella species are a leading source of bacterial gastroenteritis, causing an estimated 93.8

million cases of illness and 155,000 deaths annually. A multitude of virulence factors contribute to the ability

of Salmonella to successfully evade host defenses. Of particular interest to our research, is the ability of S.

Typhimurium to evade superoxide generated inside host phagocytic cells during systemic infection. SodCI, a

periplasmic superoxide dismutase, specifically protects against superoxide generated in the phagosome. Im-

portantly, the target of phagocytic superoxide is unknown. Contrary to dogma, our data suggest that the tar-

get is extracytoplasmic. To gain additional insight to the target(s), a global approach was taken to identify loci

that genetically interact with sodCI. Over 45,000 random transposon mutants were generated in both wild

type and a sodCI deletion strain and tested in a mouse systemic infection model. Using high throughput

22

sequencing we can compare the relative abundance of each transposon mutant before and after infection.

Identifying differences in the relative changes between wild type and the sodCI mutant background suggest

genetic interactions. After analysis of over 275 million sequencing reads, a list of the top 100 candidate genes

are currently being pursued.

cFLIPL-IRF3 interactions prevent IRF3-mediated gene expression, identifying a new function for

cFLIPL

Lauren Gates, Joanna Shisler, PhD

Members of the FLICE inhibitory proteins (FLIPs) include both viral (vFLIP) and cellular (cFLIP) proteins. This

family modulates several important innate immune responses. Two vFLIPs encoded by the molluscum conta-

giosum poxvirus inhibit IRF3 activation, begging the question whether the homologous cFLIP protein pos-

sesses a similar function. Several lines of evidence suggest that cFLIPL is a bona fide IRF3 inhibitor. Ectopic

cFLIPL expression inhibited the transcription of a synthetic luciferase gene and cellular genes controlled by

an IRF3 promoter. In contrast, the cFLIPs lacked this inhibitory function. Unlike the molluscum contagiosum

MC159 vFLIP, cFLIPL did not prevent IRF3 phosphorylation, dimerization and nuclear localization, suggest-

ing that cFLIPL functioned at a downstream step in the IRF3 activation pathway. By using chromatin immuno-

precipitation assays, it was observed that cFLIPL prevented IRF3:DNA interactions. cFLIPL co-

immunoprecipitated with endogenous and ectopically expressed IRF3, suggesting that cFLIPL prevents IRF3-

DNA interactions. Mutational analysis confirmed these interactions to be relevant. cFLIPS, an alternative

splice form of cFLIP, did not disrupt IRF3:CBP interactions, prevent IRF3:DNA interactions or inhibit IRF3 ac-

tivation. In contrast, the caspase-like domain (CLD) of cFLIPL was sufficient to inhibit all three of these

events. These data show a novel function for cFLIPL in modulating innate immune responses. To begin to

understand whether cFLIP’s IRF3 inhibitory function may also contribute to tumorigenesis, we identified that

the molecular mechanism of IRF3 inhibition occurs within the nucleus.

Understanding Emergent Behaviors of Neural Networks

S Chris Liu, Tanya Singh, Mustafa Mir, Taewoo Kim, Min Kyung Lee, Raymond Swetenburg, Sebastien Uzel,

Roger Kamm, Steve Stice, Hyun Joon Kong, Gabriel Popescu, Maribel Vasquez, Martha U. Gillette

A top-down view of engineering a biological machine is the creation of an integrated circuit capable of sens-

ing, processing, and delivering information. A bottom-up approach seeks to develop a detailed understanding

of the emergence of neural networks organically and in controlled environments that could serve as potential

substrates for the biological machines. By combining these two viewpoints, we will be able to develop an ef-

fective toolbox of circuits for the development of multiple biological machines. We have made great progress

in progress in understanding the development of neural networks. These include: understanding the emer-

gent behavior of self-organizing neural networks in primary neurons and neural stem cells using spatial-light

interference microscopy (SLIM); understanding the critical role of glia in the development, functionality, and

maintenance of neural networks; designing hydrogels to guide neurite development in a controlled manner;

and using protein patterning to harness the emergent properties of neuron development to guide axons and

dendrites.



2015 Annual Retreat

23



2015 Annual Retreat

Combinatorial Cell Microarrays for Analyzing Extracellular Matrix Regulation of Tumor Cell

Drug Response

Kerim B. Kaylan, Stefan D. Gentile, Lauren E. Milling, Kaustubh N. Bhinge, Farhad Kosari,

Gregory H. Underhill

Carcinoma progression and metastasis are directed by interactions between epithelial tumor cells and com-

ponents of the tumor cell microenvironment. Here, we have developed a high-throughput cell microarray-

based approach for investigating the impact of defined combinations of ECM proteins on tumor cell pheno-

type, function, and drug response. Briefly, A549 lung adenocarcinoma cells were seeded onto a polyacryla-

mide hydrogel substrate spotted with ECM proteins and stained for markers of apoptosis, proliferation, and

cell phenotype at endpoint. Using this approach, we quantitatively evaluated the effects of 54 different ECM

environments comprising all 2-factor combinations of 10 ECM proteins in response to a panel of drugs. We

directly compared the responses of wild-type A549 cells and A549 cells expressing ASCL1, which is associ-

ated with a subset of adenocarcinomas with aggressive behavior, and identified cell type-specific drug effects

within distinct ECM environments. These studies illustrate the capability to systematically deconstruct the

combinatorial role of ECM in tumor cell function and drug response through the application of a high-

throughput analysis platform. Continuing work utilizing this approach aims to further define the mechanisms

by which interactions with ECM drive lung carcinogenesis and resistance to drugs while integrating cell types

relevant to pulmonary neuroendocrine tumors.

Neuron-derived Insulin-like Growth Factor (IGF)-I is Necessary for Normal Cognition and Hedonic

Activity of Mice

Carlos R. Dostal, Albert E. Towers, Stephen J. Gainey, Gregory G. Freund, Keith W. Kelley,

Robert H. McCusker

The role of IGF-I and indoleamine-2,3-dioxygenase (IDO)1 in animal behavior is an expanding field, with IGF-

I and IDO1 having opposing roles. IGF-I is anti-depressive, whereas IDO1 mediates several depression-like

behaviors. The cellular sources, or targets, of IGF-I and IDO1 underpinning these roles remain poorly charac-

terized. Mice with lox-P gene inserts targeting Igf1, Ido1 or the type-1-IGF receptor (Igf1r) were bred to mice

expressing Cre-recombinase in neurons (N-Cre) or myeloid-derived cells (M-Cre) to generate knockdown

models. We hypothesized that neuronal IGF-I acts on glial IGF1R’s to modulate behavior and cognition, and

central IDO1 is required for depression-like behaviors. Cognition was assessed using object and social dis-

crimination (OD, SD) tests to evaluate recognition and exploration of novel objects or mice, respectively. Igf1/

N-Cre mice did not discriminate novel over familiar objects 1 and 24 h post-training, whereas Igf1r/N-Cre and

Ido1/N-C re mice performed poorly at 24 h. With M-Cre strains, only Igf1r/M-Cre mice under performed at 1

h. Knockdown of Igf1, Igf1r or Ido1 did not diminish performance in SD or affect anxiolytic activity (zero-maze

open-field activity). Igf1/M-Cre mice took longer to establish a preference for sucrose in the two-bottle prefer-

ence test of anhedonia, and Igf1/N-Cre mice had a prolonged recovery period following peripheral lipopoly-

saccharide (LPS) administration. These results suggest neuronal and myeloid-derived IGF-I are necessary

for hedonic activity, whereas neuronal IGF-I, IGF1R and IDO1 and myeloid IGF1R support optimal cognitive

performance in OD. Supported by the NIH with RO1 MH083767 and RO1 MH101145 to RHM and R01 SUB

UT 00000712 to KWK.

24

A Focal Point Project from 2014-2015: A Multidisciplinary Approach to Addressing Health Disparities

in Local and Global Communities

Katherine Magerko, MS, Paven Aujla, PhD, Alex Cerjanic, MS, Sam Logan, MSN,

Margarita Teran-Garcia, MD, PhD, Irfan Ahmed, PhD, Angela Wiley, PhD

During the 2014-2015 academic year, students and faculty from over thirty disciplines, local community mem-

bers from ten organizations, and students and faculty from the Autonomous University of San Luis Potosi

(UASLP), Mexico met locally and via video conferencing for a series of events on health disparities. The goal

of the project was to attract individuals from diverse fields to discuss issues pertinent to local and global

health disparities and then use newly formed collective knowledge and teamwork skills to collaborate on pro-

jects. This project was funded by the UIUC Graduate College’s Focal Point Initiative to promote new intellec-

tual communities and interdisciplinary research. Sessions included: challenges of the Affordable Care Act;

providing culturally competent care; the role of social workers and the broader context of health; mental

health access; and point of care diagnostics in resource limited settings. The project culminated in a symposi-

um on how individuals can strive to promote health equity through independent efforts in their community and

academic work. Each session included an expert to set the stage, but everyone was encouraged to take part

in the interactive discussions. Details about participants and outcomes from this project will be discussed as

well as lessons learned and future directions.

The Effect of DNA Topology on the Regulation of Salmonella Pathogenicity Island I

Koh-Eun Narm, James Slauch, PhD

Non-typhoid Salmonella are major pathogens causing gastroenteritis and enteric fever. Salmonella enterica

serovar Typhimurium colonize and invade the host intestinal epithelial cells using the Type Three Secretion

System (T3SS) encoded on Salmonella Pathogenicity Island 1 (SPI1). The level of SPI1 expression is con-

trolled by a transcriptional activator HilA. Expression of hilA is positively regulated by HilD, HilC, and RtsA,

which also activate the hilD, hilC, and rtsA genes, forming a complex feed-forward loop to control SPI1 ex-

pression. Among these, HilD has a predominant role in hilA activation, acting as a master switch that inte-

grates environmental cues, while HilC and RtsA act as amplifiers of this signal. The majority of external regu-

latory input characterized thus far requires HilD exclusively to regulate SPI1. We conducted a random muta-

genesis and identified mutations in topA, encoding DNA Topoisomerase I. They activate SPI1 expression in

the absence of HilD, HilC, or RtsA. Furthermore, in the topA background, the hilA promoter no longer re-

sponds to HilD. Thus, DNA supercoiling has profound effects on the binding of or response to transcriptional

regulators at the hilA, hilD, hilC, and rtsA promoters. Further characterization will allow us to better under-

stand the complex regulation of SPI1 and ultimately Salmonella virulence.

Resistance to Plague in 129Sv/J Mice

Michael Tencati, Richard Tapping, PhD

Yersinia pestis is the causative agent of bubonic, septicemic, and pneumonic plague. This pathogen subverts

the immune response of its host by several different mechanisms yet some hosts resist infection in a heritable

manner. Our studies with mice of the 129 background have shown that they are resistant to Y. pestis, and at

least part of this resistance maps to a 20cM region of chromosome 1. Mice containing this region were bred

with C57BL/6 mice in order to generate offspring with novel crossovers within the 20cM region, and these

were then tested in our model of plague. Results indicate the presence of at least three genes in this region



2015 Annual Retreat

25



2015 Annual Retreat

that are required for the resistance seen in the mice containing the full 20cM region. The right and left por-

tions of the region work together in trans, as shown by their ability to complement each other and restore re-

sistance when each is contributed from a different parent. One strong candidate gene in the left part of th e

region is Slc11a1, but this gene by itself is not enough to confer resistance to susceptible C57BL/6 mice, nor

is it required to maintain resistance in mice of the 129Sv/J background.

Primordial Imperatives and the Evolution of Lipid Dependent Regulation of Eukaryotic

Endocytic Trafficking

Gus Lawrence

Lysosomes solve fundamental obstacles to evolution of complex lifeforms. Lysosomes sense, maintain, and

ensure the judicious use of cellular metabolic stores. Most importantly, lysosomes maintain the membrane

which protects life from the harsh realities of the second law of thermodynamics. The primordial imperatives

of the first and second law of thermodynamics underlie the evolution of the processes regulating membrane

traffic. Membrane lipids are one of the simplest, and thus, oldest cellular signaling systems. IN eukarya, nu-

trient deprivation or osmotic stress induces the translocation of lipid modifiers to regulate endolysosomal traf-

ficking. The lipid phosphatase Pah1 responds to the nutrient stress/Tor1 pathway and promotes endolysoso-

mal progression. In contrast, hyperosmotic conditions increases PtdIns(3,5)P2 on the lysosome, activates

the yeast casein kinase Yck3, and induces the translocation of the diacylglycerol kinase (Dgk1) thereby in-

hibiting endolysomal maturation and promoting vesicular recycling pathways. This work focuses on the lipid

dependent organization of the protein machinery involved in membrane trafficking including Rab7, the gua-

nine nucleotide exchange factor Mon1, and the SNARES catalyzing membrane fusion. By examining the

mechanisms of control in their evolutionary context, one better understands the basic cellular process under-

lying diseases such as autoimmunity, Alzheimer disease, and Diabetes Mellitus.

Neonatal Exposure to Estradiol or Bisphenol-A May Alter Tanycyte Production in the

Arcuate Nucleus

Matthew J Biehl, Kirsten S Eckstrum, Lori T Raetzman

The arcuate nucleus (ARC) of the hypothalamus is a key regulator of energy homeostasis in the mammalian

brain. Classically, proopiomelanocortin (POMC) and Neuropeptide Y (NPY) neurons act in antagonistic fash-

ion to promote satiety versus hunger, respectively. Impaired development or function of either of these neu-

ronal subtypes has been previously been shown to be correlated with obesity, a major health concern in the

US and around the globe. Interestingly, a new cellular subtype within the ARC, tanycytes, has become of

interest in understanding the obesity epidemic. These specialized ependymal cells sample the environment

of the circulating cerebral spinal fluid and modulate the function of POMC and NPY neurons. Human and ro-

dent studies have suggested that maternal environment may have a negative impact on metabolic regulation

in the developing fetus, and one hypothesis is that common endocrine disrupting chemicals (EDCs) play a

role in specification of each of these cellular subtypes within the ARC. Utilizing a prenatal and postnatal dos-

ing paradigm, we have shown that estradiol and a common estrogen-like EDC, bisphenol-A (BPA), does not

appear to alter POMC or NPY neuron number within the ARC, but may increase expression of glial fibrillary

acidic protein (GFAP), one marker of ARC tanycytes.

26



2015 Annual Retreat

A D-amino acid-containing Neuropeptide Discovery Funnel

Itamar Livnat, Hua-Chia Tai, Erik Jansson, Stanislav Rubakhin, Jonathan Sweedler

Peptide isomerization is a post-translational modification that involves the conversion of one amino acid resi-

due near the C- or N-terminus of a peptide from the L-form to the D-form, resulting in a D-amino acid-

containing peptide (DAACP). This conversion, although subtle, produces significant changes in the peptide’s

3D structure and bioactivity, as well as conferring a greater resistance to degradation by peptidases. Because

isomerization does not alter the molecular weight of the peptide, it is difficult to observe by mass spectrometry

(MS) and most sequencing techniques. Thus, we have adopted alternative strategies to identify DAACPs that

take advantage of the properties conferred by isomerization. Two more promising DAACP peptide candidates

have been uncovered in Aplysia californica (where two DAACPs are known): GYFD and

SYADSKDEESNAALSDFA. Both of these peptides are peptide products of the achatin-like prohormone, the

same protein whose cleavage forms GdFFD. Because they are from the same prohormone, they may be

DAACPs as well. In particular, there is sequence homology between GYFD and GFFD, with the former pep-

tide having a tyrosine instead of a phenylalanine in the second position. Interestingly, phenylalanine and tyro-

sine have similar structures.

27



2015 Annual Retreat

Notes

28

Notes



2015 Annual Retreat

Documents

Contents · the social sciences, humanities, engineering, physical sciences, as well as the biomedical sciences. With ... Solarium 3:05pm Free Time -Guided tour with Jim Hall