EVERYONE HAS A CANCER STORY.THAT’S WHY WE DO THE RESEARCH.

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A Magazine | The School of Molecular and Cellular Biology at the University of Illinois at Urbana-Champaign | Issue 11, 2018

MCB

MCB is published by the School of Molecular and Cellular Biology

MCB DirectorMilan K. Bagchi

Managing EditorSteph Adams

Additional EditingJudith Lateer

DevelopmentTrent Reed

PhotographySteph AdamsL. Brian StaufferThompson • McClellan

DesignPat Mayer

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Produced by the MCB Communications Office for the School of Molecular and Cellular Biology. The University of Illinois is an equal opportunity, affirmative action institution.Printed on recycled paper with soy-based ink. 12.038

TA B L E O F C O N T E N T S

2 Letter from the Director, Milan K. Bagchi

4 MCB Faculty Help Lead the Cancer Center at Illinois in Collaborative, Interdisciplinary, and Translational Research

6 Benita Katzenellenbogan: Hitting the (Moving) Target of Drug Resistant Cancers

8 David Kranz: Harnessing and Boosting T-cells to Fight Cancer

10 David Shapiro: Employing the Help of the BHPI Molecule to Boost Anti-cancer Drug Treatments

12 KV Prasanth: Unveiling Cancer Connections to Long-coding RNA, MALAT1

14 Lin-Feng Chen: Taking a Deep Look at Protein Structures that Contribute to Cancer

16 Auinash Kalsotra: Exploring RNA’s Binding Role in Liver Disease and Cancer

18 Erik Nelson: Cholesterol Byproduct Hijacks Immune Cells, Lets Breast Cancer Spread

20 Alumni and Faculty Honors

22 Team Discovers How Bacteria Exploit a Chink in the Body’s Armor

23 RNA-Binding Protein, Mov10, is Key to Both Survival and Brain Function

24 Exploring the Connection Between Liver Disease and Heart Failure

25 Explaining the Liver’s Ability to Fight Against Excess Fat

26 MCB Graduates

27 MCB Learning Center for Teaching and Advising

L E T T E R F R O M T H E D I R E C T O R

2 MCB

Greetings to friends and alumni of the School of Molecular and Cellular Biology at Illinois.A change of guard in the School leadership took place last August as I became the newdirector. I would like to acknowledge the past leadership of Dr. Stephen Sligar, whoshepherded the School through fiscal challenges and led it during a decade of notablescientific advancements.

It is with great pride that I share this magazine with you. It highlights the inventive effortsof our faculty in deciphering cancer. In his Pulitzer prize-winning book The Emperor of AllMaladies, Dr. Siddhartha Mukherjee calls cancer the most elemental and magisterialdisease known to our species. In relentless battle with this malady, researchers keepinventing and reinventing, learning and unlearning strategies. Our MCB scientists areexploring new avenues to develop effective treatments for this complex disease. They areplaying important research and leadership roles in the newly established Cancer Center atUniversity of Illinois at Urbana-Champaign and contributing to the Center’s goal ofachieving national recognition and status.

This magazine also highlights the success of our research leaders in propelling brightminds and nurturing the careers of future scientists. Our graduates, with strong experiencein research and innovation, are awarded postdoctoral fellowships in major laboratories thatlead to a career in academia. They are also pursuing exciting employment opportunities inpharmaceutical industry or the government. Our undergraduates, equipped withfundamental, critical, and analytical skills imparted by MCB’s curriculum, are moving onto opportunities for further education, most notably medical school and graduateeducation in frontier areas of modern biology. The stories included in this magazine are asample of the valuable development of both graduate and undergraduate students in ourresearch laboratories.

We are committed to furthering MCB’s ability to attract and educate excellentundergraduate and graduate students, to support the continuing achievements of ourfaculty, and to promote MCB’s contribution to the overall distinction of the University. Atestimony to our strong commitment to undergraduate education is the creation of a newlearning center space, for which an update is included. The nurturing environment oflearning and discovery in the School of MCB helps build successful careers. Many of ouralumni have made great contributions to their fields with the strong foundation of anMCB undergraduate degree.

Alumni really are the key to MCB’s and the University’s success in all areas. Youraccomplishments, distinctions, and awards are a source of pride and a beacon for futurescientists. The diversity of alumni career trajectories gives our students hope and a broadervision of scientific contributions. Alumni also make it possible to retain and honor excellentfaculty and students by supporting their research and distinctions. On behalf of our facultyand students, I thank you for your support, and importantly, your continued engagementin our academic mission.

The research conducted in our school seeks the answers to fundamental questions abouthow organisms work at the molecular and systems level, how they evolve, and the resultantimplications for life, health, and disease. Our science is foundational, translational, andtransformative. I hope you will enjoy reading about the exciting work being accomplishedby our faculty, students, and alumni. n

Milan K. BagchiDirectorSchool of Molecular and Cellular Biology

Dr. Milan K. Bagchi,Director and Deborah PaulEndowed Professor ofMolecular and CellularBiology

SCHOOL OF MOLECULAR AND CELLULAR BIOLOGY 3MCB

creation of the Cancer Center will furtherstreamline and catalyze efforts and strengthencollaborations across campus, across thecountry, and even around the world.

Bioengineering faculty member and CancerCenter director Rohit Bhargava has been leadingthe efforts to organize, but many MCB faculty,including Katzenellenbogen, Roy, Bagchi,Nelson and Kranz have helped by serving inleadership and advisory capacities.

“MCB faculty are integral to the success ofthe Cancer Center by driving its scientific andeducation programs, as well as collaborations. Iam grateful for their service on our steeringcommittee and leadership in establishing thecenter,” said Bhargava.

Under the auspices of the Cancer Center,faculty members have hosted seminar series,meetings and poster sessions to increase campusnetworking and connections with other placesbattling cancer, including the Mayo Clinic andCarle Hospital.

MCB faculty collaborate with one another,and they collaborate with imaging experts whohave developed “spectroscopic expertise andhighly discriminating tools,” as well as others innutrition, for example, such as Zaynep Madak-Erdogan, and with chemists at Illinois, like John

Cancer research has been a major focuswithin MCB for decades. Faculty, includingKatzenellenbogen, Nelson, Milan Bagchi, DavidShapiro, David Kranz, K. Prasanth, Ed Roy andothers, have long focused on understanding thebiology of cancer and how to disarm it.However, cancer is a moving target. Often, onceresearchers figure out the mechanism of a givencancer and come up with ways to short circuitthat mechanism, the tumor mutates or changes

in a way to evade the cure. “Cancers change as a result of treatment,”

observes Katzenellenbogen. “That’s why there islots of interest in combination therapies. Wewant to extinguish cancer with minimal sideeffects and often combining two or more agentsor approaches is best.”

For this reason and many others,collaboration has been a byword of MCB’s basicresearch mission for a long time. As advancedtechniques, from high throughput screening andCRISPR to imaging modalities have becomeboth more common and more specialized, the

Several MCB faculty members are part of an exciting new campus unit known as TheCancer Center at Illinois. The Center is aninterdisciplinary collaborative hub with morethan 100 faculty members from departmentsranging from kinesiology, human developmentand nutrition to electrical and computerengineering, as well as graduate students andpostdoctoral researchers pursuing “cancer-related research.” The group has functioned asthe Cancer Community at Illinois since 2011.

“Campus support is always helpful to have,”said Benita Katzenellenbogen, Professor ofMolecular and Integrative Physiology and of Cell and Development Biology, of the center’sformal declaration. “It attracts outside moneyand it attracts additional colleagues. It allows for increased basic, translational, and clinicalinteractions.”

Erik Nelson, assistant professor of molecularand integrative physiology, agrees.

“As a group, we are stronger than asindividuals,” he said. Nelson, who joined thefaculty in 2014, focuses on breast and ovariancancers. His most recent work found that abyproduct of cholesterol metabolism changessome immune cells and facilitates the growth ofbreast cancer.

MCB Faculty Help Lead the Cancer Center atIllinois in Collaborative, Interdisciplinary, andTranslational Researchby Deb Aronson

Applied Research initiative) scholarships forgraduate students, pairs a student with a basiccancer research expert as a primary mentor,together with a clinician. The scholarship isjointly funded by Carle and the University.

This is one of several student opportunitiesoffered through the Cancer Center. Another one,ResearcHStart, is targeted at high schoolstudents, who work full time with facultymentors, including Nelson and MCB professorKannanganattu Prasanth, who are establishedcancer researchers.

The new Cancer Center is, above all, a highlycollaborative undertaking. And, because MCBfaculty members have a long history of extensiveand interdisciplinary collaboration, it is a perfectfit. Katzenellenbogen, for example, collaborateswith numerous groups, not only on campus,with faculty in bioengineering, food science andnutrition, but also in Korea and France andacross the United States.

In her view, interdisciplinary collaboration is,without a doubt, a key way to advance thescience of cancer. There is no down side.

“With stronger science, we make betterprogress,” she says. The Cancer Center is partof that progress. n

Katzenellenbogen, said BenitaKatzenellenbogen.

In addition to making campus-widecollaboration more effective and efficient, theCancer Center represents one of many efforts tomake MCB research even more translationalthan it has been in the past. One way that ishappening is by partnering with Carle andChristie clinics, as well as medical centerselsewhere. Carle and Christie have suppliedsamples and have helped run trials for example,says Katzenellenbogen. The Cancer Centerhelps integrate and organize these kinds ofundertakings with workshops, personnel, andstudent programs.

The next step for the center is to get NationalCancer Institute (NCI) accreditation as a cancercenter. As of 2017, there were 49Comprehensive Cancer Centers, 13 CancerCenters, and seven Basic Laboratory CancerCenters. The University of Illinois is applying tobe a basic laboratory cancer center. If it getsaccredited, it would be the only such center inIllinois. Receiving the NCI-designation placescancer centers among the top four percent of theapproximately 1,500 cancer centers in theUnited States, according to the NCI.

“This is a rigorous process, with different

categories of designation,” said Nelson, whosays the campus group is going for a basicresearch center designation similar to the onethat MIT has.

An external advisory board, comprised ofinternationally renowned experts, visited thecampus recently to evaluate the program andwere very impressed with the work being done.

“They were very enthusiastic by what we’vedone so far,” said Nelson. “Both with thescience we are doing and the current level ofcollaborations and our productivity … Weshowed that we are already rolling on manycancer-related interdisciplinary collaborationsand we showed that, while we have some greatcore facilities, the University of Illinois ispositioned to create additional unique andcutting-edge facilities, including one for tumorengineering and phenotyping.”

In addition to providing more translationalopportunities, The Cancer Center providesspecial opportunities for students. One suchinitiative, C*Star (Scholar Translational and

RESEARCH, INSPIRED BY STORIES

“As a group, we are strongerthan as individuals.”

“With stronger science, wemake better progress.”

4 MCB SCHOOL OF MOLECULAR AND CELLULAR BIOLOGY 5MCB

“These days most cancersare considered diseases onesurvives; they are not alwayslethal. The numbers ofpeople effectively treatedeven 20 years after diagnosiscontinues to increase.”

Of the ER positive cancers

that metastasize or resist

treatment, 30-40% of them

have these mutated ERs.

So, finding a way to inhibit

them would be a major

breakthrough.

understand the main drivers in cancersubtypes and to identify the best targets fortherapy,” she said. “These days most cancersare considered diseases one survives; they arenot always lethal. The numbers of peopleeffectively treated even 20 years after diagnosiscontinues to increase. Through better sub-typing of cancers we know better the risk ofrecurrence so people are better monitored andeven treated differently.”

And that is progress worth celebrating. n

(Professor Katzenellenbogen gratefullyacknowledges research support from the BreastCancer Research Foundation, the Julius andMary Landfield Cancer Research Fund, and theNational Institutes of Health.)

Chemistry to develop anti-estrogen moleculesthat might be able to inhibit the activity ofthese mutated estrogen receptors.

“Of the ER positive cancers thatmetastasize or resist treatment, 30-40% ofthem have these mutated ERs,” saidKatzenellenbogen. So, finding a way to inhibitthem would be a major breakthrough.

In another recent finding that holdspromise for some of the most difficult-to-treatbreast cancers, Katzenellenbogen’s lab hasfound an increase in the expression of thetranscription factor FOXM1, another“aggressiveness factor.”

In one recent collaboration with oncologistsin Korea, Katzenellenbogen’s lab observed anupregulation of FOXM1 in treatment-resistant cancers. Typically, FOXM1 is onlyfound at significant levels during embryonicdevelopment. When it shows up in cancer, itmakes the cancer much more robust anddifficult to treat.

“High levels of FOXM1 are associated withless good patient outcomes,” saidKatzenellenbogen.

Katzenellenbogen is interested inunderstanding the biology of thistranscription factor. FOXM1 appears to beupregulated, not only in some breast cancersbut also in other cancers, including colon andprostate that also have become resistant to

looking at certain “aggressiveness factors” thatblock treatment has motivatedKatzenellenbogen’s lab for several years.

Several effective treatments for hormonereceptor (HR)-positive cancers (whichcomprise about 70% of initial breast cancers)block the action of estrogen, turning theestrogen receptor (ER) off and thus thwartingthe cancer. In cases where this treatment stopsworking, it is often because the ER becomes“constitutively active,” which means it nolonger needs estrogen to turn on. This is oneso-called aggressiveness factor, when the ERgoes rogue, so to speak.

Katzenellenbogen’s lab has been working tounderstand how it is that the ER becomesconstitutively active and then why that makesthe cancer more resistant to treatment. Her labis collaborating with John Katzenellenbogenand his laboratory in the Department of

Benita Katzenellenbogen has delved into thecauses and treatments for breast cancer andother hormone-dependent cancers for virtuallyher entire career. Her tireless work in the fieldhas established her as a world-renownedexpert.

Lately, Katzenellenbogen, Professor ofMolecular and Integrative Physiology and ofCell and Developmental Biology, and herresearch group are “very much focused ontargeted therapies.”

Cancer treatment approaches have changedin the past decades. As researchers learn moreabout cancer biology, including identifyingsubtypes that respond to different treatments,they have figured out ways to target specificcancer cells with a more precise approach. Andthe more they understand about themechanisms at work, the more targeted thosetreatments have become, meaning that theyeffectively treat the cancer with greatly reducedside effects.

Of course, targeted therapies are not alwaysa panacea. Even with the exciting results oftargeted treatments, some cancers figure out away to make a comeback. Why and how docancers fight back? Those cancers that become“treatment-resistant” currently present one ofthe major challenges in the field. Working todescribe the biology by which cancers changein response to these targeted therapies, and

treatment, as well as some glioblastomas andgastric cancers.

“We are interested in understanding howFOXM1 works, in other words, what genesdoes it turn on, and how does that impact theinvasiveness of the cells.”

“We do know that many genes underFOXM1 regulation are genes associated withproliferation, invasiveness, and resistance totreatments,” she added.

As with the constitutively active estrogenreceptor project, Katzenellenbogen iscollaborating with John Katzenellenbogen’slaboratory to develop small molecule inhibitorsthat can effectively block FOXM1. Forexample, they are looking for compounds thatmight block FOXM1’s interaction with DNAor in some other way block its activity. Someinhibitory molecules have been identified

previously, but they are not active enough orare not selective enough, meaning theyinterfere with too many other cell activities,says Katzenellenbogen.

One finding that has Katzenellenbogenintrigued is that FOXM1 upregulation ispresent in triple-negative breast cancers. Theseare breast cancers that do not respond tohormonal therapies, including tamoxifen andaromatase inhibitors. If the action of FOXM1can be blocked, that might represent a possiblebreakthrough in treatment for this especiallychallenging subgroup of cancer, whichcomprises about 15% of all breast cancers.

Katzenellenbogen rarely stops to considerhow far the field has come, but when she does,it is to appreciate that cancer is no longer theimmediate death sentence it once was.

“We have made great progress in trying to

Benita Katzenellenbogen Lab

Hitting the (Moving) Target of Drug Resistant Cancersby Deb Aronson

Dr. Benita Katzenellenbogan, Swanlund Professor of Molecular and Integrative Physiologyand Cell and Developmental Biology. Photo by L.. Brian Stauffer

TOO MANY

SCHOOL OF MOLECULAR AND CELLULAR BIOLOGY 76 MCB

“Now you’ve basically armed the patients withbillions of T-cells that can recognize the cancer,”Kranz said.

The Kranz lab started working on ways tomodify T-cell receptors, some of the basic workthat has led to today’s cutting-edge treatments.

“We developed the methods that you couldactually try to engineer and improve thesereceptors,” Kranz said. “We’ve received 17patents, which include methods of engineering receptors as well as some ofthe receptors themselves.”

Many of the patents revolve around a technique called “yeast display,” atechnique for engineering proteins using the cell walls of yeast to single outantibodies. The technique allowed researchers to create millions of mutatedantibodies within days, and then use high-throughput screening to selectthe best candidates.

Kranz and K. Dane Wittrup (now at MIT), who had been a professor inchemical engineering at Illinois, founded a company called BioDisplayTechnologies in 1998. The company used yeast display to develop betterantibodies or other proteins such as T-cell receptors. The company wasacquired by Abbott Laboratories in 2001.

In 2008, Kranz again founded a biotechnology company calledImmuVen. ImmuVen opened in EnterpriseWorks, initially focusing ondeveloping a therapy for toxins produced by methicillin-resistantStaphylococcus aureus (MRSA), but later developing T-cell therapies forcancer. That company was acquired by a major pharmaceutical companyat the end of 2014.

Today, Kranz and his lab continue to work with T-cells, CARs, andTCRs but they also are delving into a new research area that is looking atthe development of vaccines against cancers. Vaccines are often thought ofas a preventative measure against a disease, but the goal of the work is touse them as active therapies.

An overarching goal of these types of therapeutic approaches is togenerate memory T-cells in cancer patients. Typically, these cells develop

after an immune response to infectious agents,and they kick into action if the pathogen isreintroduced. Children who contract chickenpox, for example, have memory cells that play arole in keeping them from getting the illnessagain.

Kranz believes T-cells can do the same thingwith cancer.

“We want to boost the patient’s own T-cells inthe body, activating enough of them to ‘seek and destroy’ the cancer andthen convert some of the T-cells into long-lasting memory cells,” Kranzsaid. “If you have memory cells and the cancer comes back, a patientwould have the T-cells that can eliminate the cancer.”

Kranz is working to identify the best cancer antigens to target withpotential vaccines. He is now part of the Anticancer Discovery from Petsto People theme at Illinois’ Carl R. Woese Institute for Genomic Biology.

Like many scientists whose work touches on cancer, Kranz wasn’toriginally focused on the disease. Instead, he was fascinated withimmunology and the ability to use the body’s natural defenses to treat orcure diseases and lessen or eliminate severe side effects such as thoseexperienced by patients receiving chemotherapy.

“The promise of using immunology to fight cancer was clear in the1980s. You have the potential to let the immune system go in andrecognize only the cancer cells and not the healthy cells, eliminating thoseside-effects,” said Kranz.

Over the years, Kranz studied basic molecular immunology andapplied his research to autoimmune diseases but shifted focus to cancerbecause he saw the toll the disease can have on patients and families,including his own.

“As a disease, the need for cancer therapies is so significant that wedecided to focus more on it,” Kranz said. “In immunology, we justhappened to be working on things that you could immediately see wouldhave an impact on cancer.” n

Last summer, the U.S. Food and Drug Administration approved the firstgene therapy treatment for cancer, giving hope to patients who have notbenefited from more traditional drug therapies. It’s a treatment decades inthe making, and some of the early stage work was done in the lab of DavidKranz at the University of Illinois.

Kranz, the Phillip A. Sharp Professor of Biochemistry in the School ofMolecular and Cellular Biology, has been involved in T-cell research sinceworking as a postdoctoral researcher at the Massachusetts Institute ofTechnology, involved in early discoveries about how T-cells might be usedto combat a host of diseases, including cancer. Prior to this, he trained as agraduate student at Illinois under Ed Voss, who at the time was the onlyimmunologist on campus.

T-cells are involved in the body’s immune response, destroying foreign ordamaged cells and viruses. In some cases, T-cells don’t recognize and attacklike they’re supposed to. Kranz has spent decades modifying and improvingthe receptors on T-cells to help them better target diseases and pathogens,improving the body’s immune response.

“Immunotherapies are the biggest class of new therapies for cancer byfar over anything else,” he said.

Kranz’s early work at MIT included proof-of-concept work for using T-cells to fight diseases like cancer. He and colleagues now know that T-cells can be reprogrammed to fight cancer.

At Illinois, Kranz was involved in developing bi-specific antibodies. Theproteins bind to T-cells on one end, and then attach to cancer cells on theother. The antibodies essentially act as guides for T-cells to find cancer cellsand then do their natural jobs in destroying those cells.

“People constantly develop abnormal cells, and T-cells recognize andeliminate them. We never know it’s even happening. But with cancer, thoseT-cells don’t do their jobs,” said Kranz. “We have been looking for ways toharness T-cells to act against cancer, and bi-specific antibodies are one waywe’ve done that successfully.”

There is currently one FDA-approved bi-specific antibody developed totreat lymphoma. Many others are in clinical trials.

Since the late 1990s, Kranz’s lab has also been working with T-cells forrecently approved gene therapy treatments. The technique, called CAR(chimeric antigen receptor) or TCR (T-cell receptor) T-cell therapy,involves removing a patient’s T-cells, engineering the cells to expressreceptors so they will recognize cancer cells, and then putting them backinto patients to attack those cancer cells.

Harnessing and Boosting T-cells to Fight Disease David Kranz Lab

“We have been looking for

ways to harness T-cells to act

against cancer, and bi-specific

antibodies are one way we’ve

done that successfully.”

by Brian WallheimerDr. David Kranz, Phillip A. Sharp Professor of Biochemistry

Healthy Human T-Cell

SISTER

SCHOOL OF MOLECULAR AND CELLULAR BIOLOGY 98 MCBMCB

For decades, MCB and the University ofIllinois have been at the forefront ofunderstanding the role of estrogen and theestrogen receptor (ER) in causing breastcancer. This is essential work: Breast cancer isthe most commonly diagnosed cancer inwomen, affecting roughly one in eight womenin the US alone.

MCB expertise began with the late JackGorski, co-discoverer of the estrogen receptor,the protein that estrogen must bind to in orderto work. These days MCB faculty studyingestrogen and ER include people like MilanBagchi and Benita Katzenellenbogen, whohave been here for a while, and others like ErikNelson and Kannanganattu and SupriyaPrasanth, who are relative new comers.

“MCB has been a major center forhormones and hormone action, especially as itrelates to cancer, for many years,” says DavidShapiro, inaugural Eugene E. Howe Scholar inBiochemistry. Plus, “we work well together,exchange ideas and technologies, and generallyget along well.”

Enormous strides in fighting breast cancerhave been made over the last few decades, withdrugs that target estrogen production(aromatase inhibitors) and estrogen binding toER, such as tamoxifen. Thanks in part to thesedrugs, breast cancer survival rates haveimproved.

However, although tumors often respond atfirst, cancer cells can mutate, become resistantand metastasize. Targeting these resistanttumors has become a high priority.

“This is the way of cancer,” says Shapiro.“It only very rarely can be eradicated with asingle drug. The normal thing in cancer is thattypically the tumors become resistant so youcome up with different sequential treatments.”

Shapiro began his independent researchcareer interested in the basic mechanism ofhow hormones work. As his work and the workof others began to illustrate how muchhormones affected cancer cells, he shifted hisfocus to cancer. Like many others, Shapiro haslost close family members, including hismother, to cancer.

Cancer research is a crowded field. Newtools are continually being developed and withthese new tools, new understanding pushes thefield forward. Shapiro has always been willingto seek out novel ways to look at and attack

cancer. Recently that has involved screeningtens of thousands of small molecules, notunlike looking for a needle in a haystack.

“About six years ago, I realized that therewere 200,000 papers on estrogen and in orderto discover something fundamentally differentwe’d have to try a new approach,” he says.With the help of colleagues experienced inusing the high-throughput screening facility,Shapiro’s group screened 150,000 smallmolecules.

“Instead of looking at small molecules whoseactions we could explain with currentknowledge, we’d actually study the smallmolecules whose actions we could not explain,with a view to identifying entirely new waysestrogen works,” he says. “It turned out,happily for us, that the most effective moleculeout of the 150,000 we screened worked in thisexciting new way and led us to a normalpathway of estrogen action in cancer. That’staken over most of our work.”

In other words, they found their needle. It iscalled BHPI.

In early experiments, BHPI appears to behighly effective, especially against drug-resistant cancers, precisely the cancers that arein Shapiro’s cross hairs.

BHPI was the only effective compoundfrom the screen that works through theunfolded protein response (UPR) pathway.The UPR is a protective pathway and isturned on by stress, such as an unfolded ormisfolded protein. Cancer cells use this samepathway to protect themselves from beingkilled by toxic anticancer drugs. If theprotective pathway becomes overwhelmed, i.e.more unfolded proteins than it can handle, itrevs up to a very high level, triggering a self-destruct process in the cells. Shapiro’s labshowed that estrogen bound to ER induces amoderate and protective activation of the UPRpathway in breast and ovarian cancer cells.

“BHPI hijacks this pathway and worksthrough ER to throw the UPR pathway intooverdrive, converting it from protective tolethal,” says Shapiro.

BHPI works even better in cancer cellsresistant to anticancer drugs, because the UPRpathway is already turned on as part of theway cancer cells block the toxic action ofanticancer drugs. This means that when BHPIturns the UPR up even more, those cells willtip over into the cell death pathway faster thanin cells that are not under stress. Because theUPR is typically turned off in normal cells,when BHPI turns it on, it does not tip theUPR activation into the lethal range. Thismeans healthy cells are not affected, saysShapiro.

BHPI also works by shutting down proteinsthat cells use to pump foreign compounds outof the cell. One way cancer cells becomeresistant to anticancer drugs is by using thesepumps, called multidrug resistance proteins, topump anticancer drugs out of the cells.Despite years of effort, drugs that directlyblock the action of the pumps have failedclinical trials. BHPI targets the multidrugresistance pump in a different way. One ofBHPI’s actions is to open up a compartmentwithin the cell that stores calcium. When thecell becomes flooded with calcium, proteinpumps snap into action, pumping the calcium

back into the storage reservoir. But becausethe calcium continues to leak back into thebody of the cell, the protein pumps burnthrough all the cells’ energy. Since themultidrug resistance pump also needs energyto work, it basically runs out of gas, sputteringto a stop.

Shapiro’s lab, in partnership with Nelson’slab, used a mouse ovarian cancer model that ishighly resistant to other drugs. They showedthat not only did BHPI starve the multidrugresistance pump, it enabled the original drugto work again, since it was no longer gettingpumped out of the cancer cells.

Yet another way cancer outwits anticancerdrugs is by mutating the ER. One-third ofmetastatic breast cancers have mutatedestrogen receptors; these changes areassociated with resistance to drugs. So inanother project, Shapiro used CRISPR gene-editing technology to replace the normal ERwith each of the two most common mutationsfound in metastatic cancer. His team alsotagged the cancer cells with the gene fromfireflies that enables them to light up. Usingstate-of-the-art imaging equipment, thisallowed the researchers to see, or image, thetumors inside the mice. In a small study, theyfound that BHPI was exceptionally effective.

BHPI and its cancer fighting potential iseasily one of the most exciting findings inShapiro’s long and successful career. The tricknow is to continue down the road to clinicaltrials. Those efforts include collaborating withchemistry professor Paul Hergenrother, whoseteam is engineering new small molecules thatmight work even more effectively than BHPI.There are still many complicated andexpensive steps ahead, but Shapiro isundaunted. Together with his colleagues, bothin MCB and across campus, Shapiro willcontinue to match wits with cancer. n

Left: Data-derived computer generated model of the binding of the preclinical anticancrdrug, BHPI, to its binding site near one end of the estrogen receptor (ER). BHPI binds toER at a different site than estrogen, tamoxifen and other antiestrogens (model by MaraLivezey). BHPI fits tightly into a binding cavity on the surface of ER. Unlike tamoxifen,BHPI kills breast cancer cells by acting through ER to induce lethal hyperactivation of anormally protective stress response pathway.

Dr. David J. Shapiro, Professor ofBiochemistry. Photo by L. Brian Stauffer

MOTHER

David Shapiro Lab

Employing the Help of the BHPI Moleculeto Boost Anti-Cancer Drug Treatmentsby Deb Aronson

SCHOOL OF MOLECULAR AND CELLULAR BIOLOGY 1110 MCBMCB

Kannanganattu V. Prasanth was a graduatestudent in India a little over 20 years ago whenhe was told that no one was interested in longnon-coding RNAs (lncRNAs). Some of theprofessors also lamented that there was littlefuture for studying the function of the so-called“unimportant and junk RNAs.”

But he wasn’t discouraged. “Maybe it was my young age, but I wanted to

do something that was outside the box,” saidPrasanth, a University of Illinois MCB professorof cell and developmental biology. Today, notonly is he still doing research on lncRNAs, butmany other people have jumped on thebandwagon.

“The field of lncRNA is really hot,” he said.“Everyone wants to study it,” with more than2,700 papers published on the topic in 2017alone.

Prasanth’s lab published several papers on aparticular lncRNA called MALAT1, withsignificant findings showing an important linkbetween cancer and MALAT1. They found thatwhen MALAT1 is overexpressed in breast cells,

the cells form tumors. Conversely, when it isdepleted in breast cancer cells, the cells lose theproperties necessary to produce tumors.

Prasanth also gives credit to the lab of his wifeand fellow MCB researcher, Supriya G.Prasanth, as they collaborate on this and otherprojects in both of their labs. Supriya’s lab ispursuing research on cell organization that hascancer ramifications as well.

David Spector, Prasanth’s mentor from hispostdoctoral years at Cold Spring HarborLaboratory in New York, also published a paperin 2016 showing the connection between high

levels of MALAT1 and breast cancer. Spector’slab focuses more on drug development to battlebreast cancer, making small molecules to inhibitMALAT1, while Prasanth’s lab, in contrast,concentrates on basic biology—How exactlydoes MALAT1 regulate the expression of genesin the genesis of tumors?

“MALAT1 is also present in normal cells,operating under normal conditions, so cancercells might be exploiting this to their ownbenefit. That may be why cancer cells areaddicted to high levels of MALAT1,” saidPrasanth, who has been an American CancerSociety Research Scholar since 2011.

His lab has shown that MALAT1 is found toenrich in nuclear speckles, a domain of the cellnucleus. He also discovered that it plays animportant role in regulating the activity of afamily of pre-mRNA splicing factors known asSR proteins. SR proteins themselves areoncogenic in nature—they have the potential tocause cancerous tumors. Prasanth believes thatMALAT1 contributes to cancer progression byregulating the activity of several splicing factors,

by Doug Peterson

Rising to the ChallengeK.V. Prasanth Lab Discovers Cancer Connections with MALAT1

including SR proteins.A human cell has about 2,500-3,000 copies

of MALAT1 in its nucleus, but a cancer cellshows a two to threefold increase in the copynumber of MALAT1, “and that completelychanges the dynamics,” he says. With so manycopies at work, they control more SR proteins inthe cell than normal, and the SR proteins, inturn, splice pre-mRNAs of genes that have thepotential to cause cancer.

“It’s like a puzzle,” Prasanth said. “MALAT1interacts with the SR protein here, and you havethe splicing of oncogenic pre-mRNAs there.We’re now trying to identify those oncogenicgenes whose splicing is regulated by theMALAT1-SR protein axis.”

MALAT1 seems to be involved in allsubtypes of breast cancer, he adds, but their labis focused on triple negative breast cancer(TNBC), which is one of the most aggressiveforms of breast cancer. Presently, the onlyoption to treat TNBC is through chemotherapy,but the disease becomes resistant to chemo overtime, so treatments are limited right now. That’s

why research to understand the biology ofmolecules such as MALAT1 in TNBC is crucialin order to develop next-generation drugs.

LncRNA, such as MALAT1, is longer than200 nucleotides, and it was once consideredunimportant, Prasanth says, because biologywas a protein-centric world 20 years ago. Thecentral dogma of molecular biology says thatgenetic information flows from DNA to RNA tomake proteins, which do all of the heavy liftingin cells. LncRNA upended this dogma becauseit does not code for proteins and yet it stillperforms numerous vital functions in a cell.

Back in 1995, researchers were aware of only

a few lncRNAs, but today they haveidentified over 20,000, and they havepinpointed the function of several hundredof them.

Prasanth started his work on MALAT1in 2005 while in Spector’s lab at ColdSpring Harbor, but with his mentor’sblessing he brought this research to the Uof I when he and his wife came to Urbanaas MCB professors in 2007. Today,Prasanth and Supriya have labs side-by-side in the Chemical and Life SciencesBuilding, and their students work togetheras one unit, even though each lab pursuesits own unique projects. As Supriya andPrasanth continue to collaborateextensively on several ongoing researchprojects, they also challenge each other.

“That’s the way science works,”Prasanth poined out. “You always need tobe challenged.” n

MALAT1 is present in

normal cells, operating

under normal conditions,

so cancer cells might be

exploiting this to their

own benefit.

We’re now trying to

identify those oncogenic

genes whose splicing is

regulated by the MALAT1-

SR protein axis.

TOO MANYSuper resolution imaging of a humanfibroblast nucleus reveals ordered assembly ofoncogenic MALAT1 lncRNA (red), SR splicingprotein (blue) and the pre-mRNA splicing U2snRNA (green) in nuclear specklesub-nuclear domains.

Dr. K.V. Prasanth, Professor of Cell and Developmental Biology

12 SCHOOL OF MOLECULAR AND CELLULAR BIOLOGY 13

“These are exciting findings.

This is very translational

research.”

Thirteen years ago, when Lin-Feng Chenjoined the Department of Biochemistry, he hadhis sights set on a specific protein that could bothcontribute to the growth of cancer and be amajor factor in boosting the body’s immunesystem.

“The protein in question was NF-kappaB(nuclear factor kappa-light-chain-enhancer ofactivated B cells), a kind of “master controller” ofinnate and adaptive immune response, and cellsurvival,” explains Chen.

In healthy cells, it spends most of its life in thecell’s cytoplasm, quietly awaiting orders to assistthe immune system. In response to viral andbacterial infection, NF-kappaB moves into thenucleus and triggers the expression of manygenes that help to fight against infection. Aftereliminating the pathogens, NF-kappaB returns tothe cytoplasm, awaiting the next order. However,NF-kappaB can work against the body’s bestinterests, too. Sustained nuclear NF-kappaB isassociated with a variety of inflammatory diseasesand cancers.

Dr. Chen’s postdoctoral work at the GladstoneInstitute of Virology and Immunology atUniversity of California at San Francisco focusedon the post-translational regulation of NF-kappaB in immunity and cancer. What chemicalmodifications were needed to make NF-kappaBdormant, until needed, in healthy cells and runamok in diseased cells?

That work identified acetylation, a chemicaltag that can be added to lysine, of NF-kappaBthat dictates the transcriptional outcome of NF-kappaB. So the major question when Dr. Chenstarted his lab at the University of Illinois was tofind out how the modification of lysines affectedthe activity of NF-kappaB.

At that time there were some clues that theacetylated lysine can control the protein’s activity

through a signaling partnership with abromodomain, a pocket-like structure, that canaccommodate acetylated lysine and change theproperties of the proteins.

“We stared to look for bromodomains thatmight recognize the acetylated lysine of NF-kappaB and proteins that contain such a domaincould be working with NF-kappaB,” said Chen.In 2009, Chen’s group identified bromodomain-containing protein 4 (BRD4) as a co-activator ofNF-kappaB, specifically recognizing theacetylated lysine of NF-kappaB via itsbromodomains.

This discovery launched a decade of work inChen’s lab focusing on BRD4’s role ininflammation and cancer.

BRD4 belongs to a class of molecules that canrecognize specific chemical tags on other proteinsto spur the marked proteins to perform varioustasks. Chemical tag "readers" such as BRD4 areimportant players in the field of epigenetics,which focuses on how specific genes areregulated.

"In epigenetics, there are writers, there arereaders, and there are erasers. BRD4 is thereader," Chen said. The writers and erasers addor remove tags to or from proteins, withoutchanging the underlying sequence of the genethat codes for them. Drugs targeting epigeneticregulators have emerged as novel therapies incancer treatment, and a number of small-molecule inhibitors against epigenetic regulatorshave already been developed for cancer therapy.

Exploring the role of BRD4 in cancer, Chen’sgroup found that BRD4 prevents thedegradation of nuclear NF-kappaB by binding toacetylated NF-kappaB, and contributing to thesustained presence of NF-kappaB in the nucleusof cancer cells. They also found that a smallmolecule, JQ1, which blocks the interaction

between BRD4 and NF-kappaB, reducedproliferation of cancer cells and suppressed theability of cancer cells to form tumors.

“These findings opened exciting possibilitiesfor translational research. The interactionbetween BRD4 and NF-kapapB could be atarget for therapies to stop the spread of canceror inflammatory disease,” said Chen.

Chen’s lab recently discovered that there was ahigher expression of BRD4 in gastric cancer cellsand in gastric cancer patient samples. Theyidentified an enzyme, PIN1, the expression ofwhich was highly correlated to BRD4 in gastriccancer cells and regulated the tumor-promotingactivity of BRD4 in gastric cancer cells. They alsofound that BRD4 promoted gastric cancer cellproliferation by preventing the cell senescence.

Chen’s latest research is delving even deeperinto the physiological role of BRD4 in cancer andinflammation. A recent paper in Oncogenedemonstrated that removing BRD4 from specificmouse tissues compromised the mice’s innateimmunity to find against bacterial infection andtumor. With these tissue specific BRD4-deficientmice, they have tried to determine thecontribution of BRD4 in inflammatory diseasesand inflammation-associated cancer.

Various inhibitors targeting BRD4 areundergoing clinical trials for the treatment ofcancer and inflammatory diseases. “Our studieswill provide new insights for developing therapiestargeting BRD4,” said Chen. “This is verytranslational research.”n

SISTER, MOTHER

Lin-Feng Chen Lab

Taking a Deep Look at ProteinStructures that Contribute toCancer by Steph Adams

Binding of bromodomain 2 of BRD4 toacetylated lysine of NF-kappaB

Dr. Lin-Feng Chen, Professor of Biochemistry

14 MCB SCHOOL OF MOLECULAR AND CELLULAR BIOLOGY 15

Auinash Kalsotra Lab

by Brian Wallheimer

Kalsotra knew that RNA binding proteins played a role in theformation of mRNA, so his lab started knocking out these proteins frommouse livers to study their functions.

In liver cells, mice that lost certain RNA binding proteins starteddisplaying signs of fatty liver disease. The condition is common amongpeople who abuse alcohol, but also affects more than 100 million peoplein the U.S. and more than a quarter of people in the non-developed worldas non-alcoholic fatty liver disease.

“One-third of people with non-alcoholic fatty liver disease get anaggressive form of the disease,” Kalsotra said. “In addition to having fat intheir livers, they’re going to have a lot of inflammation, scarring and livercell death.”

The mice eventually developed liver cancer. It got Kalsotra’s lablooking for connections between genes and non-alcoholic fatty liverdisease. Analysis revealed that the genes that ranked highest as likelycontributing to the disease are associated with RNA splicing.

“Our goal in knocking out these genes was to understand how thesecells mature and how RNA splicing plays a role in tissue development,”Kalsotra said. “Instead, what we saw was a very specific disease that seemsto match a human phenotype.”

Kalsotra collaborated with the Carle Hospital to analyze biopsy samplesof patients with non-alcoholic fatty liver disease. Each patient showed astriking decrease in RNA binding proteins.

The findings raise more questions, such as whether the loss of RNAbinding proteins leads to the liver disease and cancer. It’s possible that lossof RNA binding proteins could be a biomarker for fatty liver disease andcancer. Or maybe the opposite is true, that loss of the binding proteins is aresult of the liver diseases.

Auinash Kalsotra wasn’t originally interested in studying cancer. Infact, he wasn’t looking to study any particular disease at all.

Kalsotra wanted to know how the complex machinery of our bodiestakes the codes embedded in our DNA and turns them into healthy organtissues, specifically heart and liver. In other words, he wanted to knowhow things worked — not why they break or how to fix them.

“There’s a molecular logic to how cells are put together, howsomething becomes a nerve or muscle cell,” Kalsotra said. “Once thesecells have features, how do they mature and give rise to a functioningadult tissue that carries out a particular function?”

But as often happens, scientists start on one path and eventually findthemselves pulled onto others. In this case, Kalsotra’s search for a deeperunderstanding of cellular mechanisms has led to significant findings thatshow linkages between liver diseases and cancer and may improve ourunderstanding of the origin of these diseases.

Kalsotra’s research has focused on RNA, the workhorse cousin ofDNA, which makes up the genetic instructions for living things. RNA isoften viewed as important for messaging and other functions, takingDNA’s code and transporting it to and carrying out functions in cells. It’soften taken a back seat to DNA in terms of significance.

In particular, Kalsotra is intrigued by the fact that one gene can giverise to multiple types of RNA based on the type of cell it will encode. Along stretch of RNA will be cut into pieces, called exons, which arespliced together to form messenger RNA (mRNA). The pieces splicedtogether, their order and other factors determine the type of function theRNA will carry out.

“That means one gene can give rise to multiple mRNAs, and thosemRNAs are dependent on the cell type,” Kalsotra said.

Kalsotra also wants to know if and how the cancer profiles in mice matchwith humans, who tend to get cancer after fatty liver diseases. And whetherthere are mutations in genes from birth that lead to liver disease and cancer,or whether there are environmental triggers, such as diet, that are involved.

In addition, the Kalsotra Lab is looking at how the transition from thebody making fetal cells to making adult cells might play a role in cancerformation. Fetal cells rapidly proliferate, much like cancer cells. But at somepoint, the body switches to making adult cells — a few years after birth inhumans and a few weeks in mice.

That switch coincides with the creation of adult versions of mRNAs fromthe same genes. It’s possible, then, that a malfunction in the production ofthese “adult mRNAs” could reinitiate cell proliferation, a hallmark of cancer.

“What we’re seeing is that it may not only be at the level of mutation in agene that controls cell proliferation or activating an oncogene that gives acancer cell an advantage to grow, but also what kind of mRNAs you make,”Kalsotra said. “If you impinge on that regulation, you now produce thewrong kinds of mRNAs that might not be good for that cell at that stage.”

While Kalsotra wasn’t aiming to study cancer, there is a sense ofsatisfaction knowing that his work might have an impact on the disease. Hisbrother-in-law has advanced-stage esophageal cancer, and the work hasbecome somewhat more personal. His overall goal is to understand theproper function of RNA splicing, but there is an incentive to furtherexploring the malfunctions as well.

“It kind of gives me extra motivation to see why normal cells all of thesudden become cancerous,” he said. “Maybe one day, if we understand hownormal cells work, we can understand what goes wrong in a cancer cell thatmakes it divide uncontrollably and not listen to the rest of the organ that istelling it to stop growing.” n

Exploring RNA’s Binding Role inLiver Disease and Cancer “Maybe one day, if we understand how

normal cells work, we can understand whatgoes wrong in a cancer cell that makes itdivide uncontrollably and not listen to therest of the organ that is telling it to stopgrowing.”

BROTHER-IN-LAW

The Kalsotra Lab has discoveredthat deletion of a splicing factorresults in spontaneousdevelopment of nonalcoholicSteatohepatitis (NASH) in micerevealing an unexpected linkbetween splicing deregulationand fat metabolism in the liver.

Dr. Auinash Kalsotra, Professor of Biochemistry

16 MCB SCHOOL OF MOLECULAR AND CELLULAR BIOLOGY 17

HO

OH

MOTHER-IN-LAW,GRANDMOTHER,

GOD-FATHER, COUSIN,

GREAT-AUNT, TOO MANY FRIENDS

by Liz Ahlberg Touchstone, News Bureau

High cholesterol levels have been associatedwith breast cancer spreading to other sites inthe body, but doctors and researchers don’tknow the cause for the link. A new study byUniversity of Illinois researchers found that theculprit is a byproduct of cholesterolmetabolism that acts on specific immune cellsso that they facilitate the cancer’s spreadinstead of stopping it.

The study, published in the journal NatureCommunications, identifies new potential drugtargets that could inhibit the creation or actionsof the dangerous cholesterol byproduct, amolecule called 27HC.

“Breast cancer impacts roughly 1 in 8women. We’ve developed fairly good strategiesfor the initial treatment of the disease, butmany women will experience metastatic breastcancer, when the breast cancer has spread toother organs, and at that point we really don’thave effective therapies. We want to find what

drives that process and whether we can targetthat with drugs,” said Erik Nelson, a professorof molecular and integrative physiology wholed the study.

Nelson’s group fed mice with breast cancertumors a diet high in cholesterol. Theresearchers confirmed that high levels ofcholesterol increased tumor growth andmetastasis, and that mice treated withcholesterol-lowering drugs called statins hadless metastasis. Then they went further,specifically inhibiting the enzyme that makes27HC during cholesterol metabolism.

“By inhibiting the enzyme that makes

27HC, we found a suppressor effect on breastcancer metastasis. This suggests that a drugtreatment targeting this enzyme could be aneffective therapeutic,” said Amy Baek, apostdoctoral researcher at Illinois and the firstauthor of the paper.

The researchers also saw unusual activityamong specific immune cells—certain types ofneutrophils and T-cells—at metastatic sites highin 27HC.

“Normally, your body’s immune system hasthe capacity to attack cancer,” Nelson said,“but we found that 27HC works on immunecells to fool them into thinking the cancer isfine. It’s hijacking the immune system to helpthe cancer spread.”

Because 27HC acts through the immunesystem, and not on the breast cancer itself, theresearchers believe their findings have broadapplicability for solid tumors. They performed

experiments looking at colon cancer, lungcancer, melanoma and pancreatic cancer, andfound that 27HC increased metastasis for allthe tumor types, suggesting that a treatmenttargeting 27HC could be effective acrossmultiple cancer types.

The researchers are working to furtherunderstand the pathway by which 27HCaffects the immune cells. With clinical partnersat Carle Foundation Hospital in Urbana, theteam is working to establish whether 27HC hasthe same pathway in human patients as inmice.

“We hope to develop small-molecule drugsto inhibit 27HC,” Nelson said. “In themeantime, there are good cholesterol-loweringdrugs available on the market: statins. Cancerpatients at risk for high cholesterol might wantto talk to their doctors about it.”

Nelson also is affiliated with the Cancer

Center, the division of nutritional sciences, andthe Carl R. Woese Institute for GenomicBiology at Illinois. The National Institutes ofHealth and the Susan G. Komen Foundationsupported this work. n

Cholesterol Byproduct Hijacks ImmuneCells, Lets Breast Cancer Spread

“By inhibiting the enzyme

that makes 27HC, we found

a suppressor effect on

breast cancer metastasis.”

Postdoctoral researcher Amy Baek, professorErik Nelson and breast cancer survivor SarahAdams. Photo by L. Brian Stauffer

“Normally, your body’s

immune system has the

capacity to attack cancer,”

but we found that 27HC

works on immune cells to

fool them into thinking the

cancer is fine.”

SCHOOL OF MOLECULAR AND CELLULAR BIOLOGY 1918 MCBMCB

Robert Gaynes, adistinguished doctorknown for his effectiveteaching and mentorshipof medical students, hasbeen chosen as a 2017Illini Comeback Guestby the University of

Illinois Alumni Association.Robert P. Gaynes (BS, ’75, biology-honors),

professor of medicine and infectious diseases atEmory University, professor of epidemiology atthe Rollins School of Public Health, and anattending physician at the Atlanta VeteransMedical Center, said that it’s a thrill to be comingback to campus.

“There were a couple decisions I made as anundergraduate student at the University ofIllinois that I reflect back on as being quiteinfluential in my life,” Gaynes said..

After receiving his degree from Illinois,Gaynes went on to receive his medical degreefrom the University of Chicago Pritzker Schoolof Medicine. Since then, Gaynes has served as aconsultant to the World Health Organization andthe Joint Commission on Accreditation ofHealthcare Organizations, earned induction intothe Academy of Medical Educators for histeaching and mentorship of medical students,and hosted the Centers for Disease Control andPrevention’s (CDC) Morbidity & MortalityWeekly Report podcast.

Gaynes said majoring in the Honors BiologyProgram gave him a solid academic backgroundin the field, as well as an opportunity to workclosely with others. As an undergraduate, Gaynesand 13 other students spent an entire threesemesters taking courses together under theguidance of one professor.

“We all got to know each other quite well. Welearned basic biology and learned criticalthinking,” Gaynes said. “It really wascollaborative science. Medicine today is a teamsport — you really work with a variety of alliesand medical professionals. That collaborativeapproach is something I got out of HonorsBiology.” n

Biology Alumnus ReceivesIllini Comeback Award

Joanne Chory (PhD Microbiology '84) is currently a plant biologist atthe Salk Institute for Biological Sciences.

Chory, one of the world’s preeminent plant biologists who is nowleading the charge to combat global warming with plant-based solutions,has been awarded a 2018 Breakthrough Prize for her pioneering workdeciphering how plants optimize their growth, development and cellularstructure to transform sunlight into chemical energy.

The prestigious award, founded in 2013 by Silicon Valley luminariesSergey Brin and Anne Wojcicki, Mark Zuckerberg and Priscilla Chan, and Yuri and Julia Milner,honors top achievements in life sciences, physics and mathematics.

Chory, a professor and director of the Plant Molecular and Cellular Biology Laboratory at theSalk Institute for Biological Studies, received the prize, which included a $3 million award, onDecember 3 at a televised event at the NASA Ames Research Center in Mountain View,California.

“By celebrating science and recognizing its importance to our world, the visionary founders ofthe Breakthrough Prize are having a significant impact on promoting life-changing discovery andencouraging bright young minds to bring their talents to these exciting fields,” says Chory, who isalso a Howard Hughes Medical Institute Investigator and holder of the Howard H. and Maryam R.Newman Chair in Plant Biology. “I’m truly honored to receive this award, humbled to be in suchdistinguished company and tremendously gratified that the study of plants, which is essential todeveloping everything from better agricultural practices to mitigating global warming, has been putin the spotlight with this award.”

Chory joined the faculty of the Salk Institute in 1988 as one of the first plant biologists at theInstitute. In 2003, she was named Scientific American’s Research Leader in Agriculture, and in2016 she made Thomson Reuter’s list of the World’s Most Influential Scientific Minds. She is amember of the U.S. National Academy of Sciences, the German National Academy of Sciences(Leopoldina), the American Philosophical Society, the American Academy of Arts and Sciences,and is a fellow of the American Association for the Advancement of Science. She also is a foreignmember of the Royal Society of London and a foreign affiliate of the French Academy of Science.

Dr. Chory did her PhD research in the lab of Samuel Kaplan, former Chair of Microbiologyand Director of the School of Life Sciences. n

Microbiology Alumna Wins the 2018 BreakthroughPrize in Life Sciences

Alumnus Thomas Cycyota Receives AmericanAssociation of Tissue Banks Award

Cycyota received the Jeanne C. Mowe Distinguished Service Award,which recognizes an individual who has made a significant contribution intissue banking or transplantation, whether in research, education, orlaboratory improvement, or who has served the Association or the field oftissue banking.

Biology alumnus (’80), Thomas Cycyota is the President and CEO ofAlloSource, one of the nation's largest providers of cartilage, bone, skin,

soft-tissue and cellular allografts for use in surgical procedures and wound care to advance patienthealing.

Under his leadership, the organization has grown into a leading provider of allografts for use inspine, sports medicine, foot and ankle, orthopedic, reconstructive, trauma and wound careapplications. AlloSource continues to identify new opportunities to create innovative products thatadvance patient healing.

In 2015 Cycyota was also awarded the LAS Alumni Humanitarian Award. He considers thedonation of tissue to be a “sacred gift.” “Everybody understands organ donation because a heart ofkidney saves somebody’s life,” he said. “But with tissue donation, a donor who has passed away canaffect hundreds of people.”n

Faculty HonorsAlumni Honors

SCHOOL OF MOLECULAR AND CELLULAR BIOLOGY 2120 MCB

Emad TajkhorshidNamed the J. WoodlandHastings Endowed Chairin Biochemistry

Emad Tajkhorshid is a professor ofbiochemistry, biophysics and quantitativebiology, pharmacology, and bioengineering.He is also interim head of the Department ofBiochemistry and is the director of the NIHBiotechnology Center for MacromolecularModeling and Bioinformatics..He was chosenfor the award by a committee of his seniorcolleagues who hold endowed positions. He isa member of the Beckman Institute forAdvanced Science and Technology.

This endowed chair is named for the lateJohn Woodland “Woody” Hastings (1927-2014), and set up by donors George andTamara Mitchell. Hastings was a decoratedscholar who served as a faculty member atIllinois from 1957-66 and was best known forhis innovation in the field of bioluminescence.He was also a founder in the field of circadianbiology, focusing on the biological cycles ofplants, animals, fungi, and other living things.

Tajkhorshid has authored over 180 researcharticles, including over 17,500 citations inhigh-profile journals such as Nature, Science,eLife, and PNAS. He has delivered nearly 150invited lectures at international meetings,universities, and research institutes. He serveson the editorial boards of multiple journals,including Biophysical Journal, Journal ofBiological Chemistry, and PLoSComputational Biology.

“Most importantly, I would like toacknowledge my students, post-docs andcolleagues,” Tajkhorshid said. “They are thereason I’m standing here, presenting what theyhave been doing for many, many years; I reallyappreciate and enjoy working with them.”

Satish Nair Named I.C.Gunsalus Professor in theCollege of Liberal Arts &Sciences

Satish Nair, a professor of biochemistry in theSchool of Molecular and Cellular Biology anddirector of the Center for Biophysics andQuantitative Biology, is a leader in studying howbacteria can make antibiotics and othermedicinally relevant molecules.

The professorship is named in honor of thelate I.C. Gunsalus, who joined the University ofIllinois as a professor of microbiology in 1950.In 1955, he became head of the biochemistrydivision in the Department of Chemistry. Hetaught and researched at Illinois for 32 years.

Nair’s lab conducts research that allows forcertain drugs to be produced in test tubes andfacilitates production of drug derivatives that donot exist in nature. This research will helpdevelop new classes of therapeutics for thetreatment of infections from drug-resistantbacteria. Nair has served on various reviewpanels around the world, and his laboratory hastrained more than 50 undergraduate students,almost all of whom have gone on to advancedcareers in science.

“This professorship means a lot to me andone of the things it provides is independence forwork that is not yet funded,” Satish said. “Mylab is very interested in expanding what we do,and moving on to doing new things and movingon to new areas of science is not somethingyou’d get money for except for this endowedappointment.”

Llano BecomesProfessorial Scholar

Dan Llano, associate professor in molecularand integrative physiology and member ofBeckman's Neurotechnology of Memory andCognition Group, was recently appointed theBenjamin R. and Elinor W. Bullock and Edwin E.and Jeanne Bullock Goldberg ProfessorialScholar in the Department of Molecular andIntegrative Physiology in the School ofMolecular and Cellular Biology.

Dr. Edwin Goldberg, M.D., and Dr. JeanneBullock Goldberg, M.D., established theprofessorship to enhance the opportunity forUniversity of Illinois faculty scholars to conductresearch that is novel, translational, andsustainable.

Dr. Llano is a leader in his field investigatingthe neuronal circuits in the midbrain, thalamus,and cortex that participate in the processing ofauditory information. He has developed a well-respected research program designed tounderstand cellular and network mechanisms ofauditory processing and alterations associatedwith pathology of this system. His laboratory hasmade several innovative advances to study thecomplex interaction between key areas ofauditory function. In addition, he has usedcomputational approaches to constructpredictive models that can be used to betterunderstand normal and pathological functions ofthe auditory circuitry. Using these tools, Dr.Llano has made significant contributions to thefield through fundamental new discoveriesregarding the structural and functionalorganization of auditory feedback pathways andthrough the generation of novel hypothesesregarding the underlying information processingprinciples. His studies also established theauditory cortex as a primary site of pathologyduring both normal aging and in the setting oftinnitus (ringing in the ear). n

MCB

A study led by Dr. Geena Skariah, a recentNeuroscience graduate of the Ceman lab in Celland Developmental Biology, and currentpostdoctoral researcher at the University ofMichigan, revealed the importance of the proteinMov10 (Moloney leukemia virus 10) inneurological development in animals. The findingswere published in BMC Biology.

The study began with an idea from fellowgraduate student in the Ceman lab, Miri Kim.“Why don’t you look at the brain over time andsee what happens with the protein Mov10?”she asked. “It was a novel question because Mov10 has

been characterized only in cell lines as an RNAhelicase and as a regulator of retrotransposons,”said Dr. Stephanie Ceman. “No one was reallylooking at its effect on the brain.”Skariah was intrigued. She walked over to

the lab of Dr. Auinash Kalsotra, a biochemistwho, along with Dr. Ceman, focuses on RNAbiology. Skariah knew that the Kalsotra lab wasworking on cytosolic poly(A)-binding protein 1(PABPC1) in the livers and hearts of mice andasked if they would be willing to shareresources. “We both share the interest in how RNA

brings things together and makes the cells andtissues in our bodies work,” said Dr. Kalsotra.From the resources available in the Kalsotra

lab, Skariah was able to test post-mortembrains of mice at different points in theirdevelopment and measure the level of Mov10. “We saw that Mov10 goes up during

development and goes back down in the adult,”said Skariah. “That was my first piece of realdata.”No one had ever looked at Mov10’s role in

the development of the brain, and this was a

completely new finding. “That finding startedoff this whole project,” said Skariah.Mov10 was thought to be unimportant to

brain function because there are usually lowlevels of it found in adult brain. “I didn’t think they were going to see

anything. I didn’t say not to do it, but I did sayit was not going to work,” admitted Dr. Ceman,with a laugh.But Skariah was able to convince Dr. Ceman

with the impact of her first results. “That’s great!” Ceman said. “Now test it in

different sexes and with different strains.”“Every single day. Over and over and over!”

quipped Dr. Kalsotra.The initial finding opened the door to a

cascade of questions. Why is this protein goingup in early development? What is it is doing inthe brain?“What’s fun about this,” said Ceman, “it’s

the biggest discovery project I have been part ofin a long time.” Every time they did anexperiment in this project, they had no ideawhat they were going to find. Further experiments showed that reduced

levels of the protein resulted in behavioralchanges that suggested neurologicalimpairment. They were seeing several defects inthe cells, but where were they coming from? Toaddress this question, they moved to aneuroblastoma cell line (Neuro2A), on whichthey could use CRISPR-Cas9 to remove bothcopies of Mov10. Then they examined theeffect of Mov10 loss on total RNA levels andon the ability to grow a neurite, Cemanexplained. “They sequenced the cellular RNA millions

of times at the Carver Biotech Center oncampus and obtained a huge amount of datashowing a lot of differences in the RNA levels,”

said Kalsotra. “We all started to talk about whatto make of it and delve into the data.”The Ceman and Kalsotra labs have an RNA

journal club that meets every week, andthrough this club, Skariah learned that JosephSeimetz, in the Kalsotra lab, could help withthe bioinformatics on this project. “There is a list of gene candidates, and you

can’t test every one because there arethousands of them,” said Skariah.“Bioinformatics is so powerful because you canpick important ones and remove them from thecell.”“The Ceman lab basically did all the work,”

said Seimetz. “It was perfect timing. We hadstarted to build our own bioinformaticspipelines for analyzing “Big Data,” so wecombined it with our work.” “Joe developed the graphics that were so

important for the paper,” said Skariah. “Wecould move from a point of taking out genes toa point where we see a phenotype, we remove itand see how the genes change and how theyfunction.”There is a lot more research that can come

from this data. Their next step is to see whathappens when Mov10 is removed from thebrain. The lab is continuing to look at how thereduction of Mov10 changes the neurons.The findings were published in BMC

Biology, and the paper has piqued significantinterest, with nearly 5000 views in the last sixmonths.Seimetz’s work organizing the sizable

amounts of data collected during the project isnow shared in a public database that allowsscientists around the world to work with anduse the data. “It’s like our data keep on giving,” Dr.

Ceman said. n

RNA-BindingProtein, Mov10, is Key to BothSurvival and Brain Function

by Steph Adams

Scientists have discovered how a unique bacterial enzyme can blunt thebody’s key weapons in its fight against infection.

Researchers at the University of Illinois at Urbana-Champaign andNewcastle University in the U.K. are investigating how infectious microbescan survive attacks by the body’s immune system. By better understandingthe bacteria’s defenses, new strategies can be developed to cure infectionsthat are currently resistant to treatments, the researchers said.

The study, reported in the journal PLOS Pathogens, focused on thebacterium Staphylococcus aureus, which is found on approximately half ofthe population. While it usually safely coexists with healthy individuals, S.aureus has the ability to infect nearly the entire body; in its most pathogenicform, the bacterium is the so-called “superbug” methicillin-resistant S.aureus, or MRSA.

The human body uses a diverse array of weapons to fight off bacteria likeS. aureus. “Our immune system is very effective and prevents the majorityof microbes we encounter from causing infections,” said U. of I.microbiology professor Thomas Kehl-Fie, who led the study with KevinWaldron, of Newcastle University. “But pathogens such as S. aureus havedeveloped ways to subvert the immune response.”

S. aureus can overcome one of the body’s key defenses, nutritionalimmunity, which prevents bacteria from obtaining critical nutrients. Itstarves S. aureus of manganese, a metal needed by the bacterial enzymesuperoxide dismutase, or SOD. This enzyme functions as a shield,minimizing the damage from another weapon in the body’s arsenal, theoxidative burst. Together, the two host weapons usually function as a one-two punch, with nutritional immunity weakening the bacteria’s shields,enabling the oxidative burst to kill the bacterium.

S. aureus is particularly adept at causing devastating infections. Differingfrom other closely related species, S. aureus possesses two SOD enzymes.The team discovered that the second SOD enhances the ability of S. aureusto resist nutritional immunity and cause disease.

“This realization was both exciting and perplexing, as both SODs werethought to utilize manganese and therefore should be inactivated bymanganese starvation,” Kehl-Fie said.

The most prevalent family of SODs, to which both of the S. aureusenzymes belong, has long been thought to come in two varieties: thosethat are dependent on manganese for function and those that use iron.

In light of their findings, the team tested whether the secondstaphylococcal SOD was dependent on iron. To their surprise, theydiscovered that the enzyme was able to use either metal. While theexistence of these cambialistic SODs, capable of using both iron andmanganese, was proposed decades ago, the existence of this type ofenzyme was largely dismissed as a quirk of chemistry, unimportant in realbiological systems. The team’s findings dispel this notion, demonstratingthat cambialistic SODs critically contribute to infection.

“We found that, when starved of manganese by the body, S. aureusactivated the cambialistic SOD with iron instead of manganese, ensuringits critical bacterial defensive barrier was maintained,” said Yuritzi Garcia,senior graduate student and a lead author on the study. “By learning howS. aureus’s defenses work we are able to better understand the innerworkings of this human pathogen,” she said.

“The cambialistic SOD plays a key role in this bacterium’s ability toevade the immune defense,” Waldron said. “Importantly, we suspectsimilar enzymes may be present in other pathogenic bacteria. Therefore, itcould be possible to target this system with drugs for future antibacterialtherapies.”

The emergence and spread of antibiotic-resistant bacteria, such asMRSA, make such infections increasingly difficult, if not impossible, totreat.

This has prompted leading health organizations, such as the Centers forDisease Control and Prevention and the World Health Organization, toissue an urgent call for new approaches to combat the threat of antibioticresistance. n

Dr. Thomas Kehl-Fie, Assistant Professor of Microbiology andYuritzi Garcia, graduate student

Dr. Stephanie Ceman (cell and developmental biology), Dr. Auinash Kalsotra(biochemistry), Dr. Geena Skariah (Ceman lab), and Joseph Siemetz (Kalsotra lab)by Serina Taluja

Staphylococcus aureus, in yellow, interacts with a human whiteblood cell. Photo courtesy the National Institute of Allergy andInfectious Disease

22 MCB

Team Discovers How Bacteria Exploit a Chink in the Body’s Armor

SCHOOL OF MOLECULAR AND CELLULAR BIOLOGY 23MCB

“The discovery that excess bile acid affectsheart metabolism was a big step forward, sincethis could allow us to identify potential treatmentoptions,” said Anakk.

Based on these findings, Ms. Mathur testedwhether reducing bile acid levels would besufficient to reduce the heart defect. They treatedthe mouse model with Cholestyramine, an FDAapproved drug to treat high cholesterol that canremove bile acids from the blood, and found thatthe use of Cholestyramine protects against heartfailure.

The team, with Dr. Moreshwar Desai, apediatrician at Texas Children’s Hospital and firstauthor with Bhoomika Mathur, undertook thisstudy. “The curative potential is exciting, but wehave many more questions for bile acid’s role incardiac malfunctioning,” said Anakk. n

Infants and children with liver diseases aremore likely to succumb to heart failure than toliver failure, and in fact, the heart’s health oftenimproves after a liver transplant. New researchfrom the Annak lab, published in the journalHepatology, demonstrates that excess bile acids inthe liver cause metabolic change and stress in theheart. “That there is a connection between liverand heart disease has been known for hundredsof years,” said Dr. Sayee Anakk, assistantprofessor of Molecular and IntegrativePhysiology, whose lab studies the regulation ofmetabolic signaling in the liver. “High levels ofbile acids in diseased livers is associated withconsequent cardiac dysfunction, but we do notknow the mechanisms responsible for thatconnection.”

Using mouse models that resembled the

Exploring the Effect of Liver Disease on the Heart

In a second paper, the Anakk labexplored the mechanism by whichthe liver can be protected fromdeveloping fatty liver disease. Thiswork was also published inHepatology and led by two formerundergraduates of the MCBprogram, Oludemilade Akinrotimi(Demi) and Ryan Riessen alongwith another MCB alumnus, PhilVanduyne. Using the sameexperimental mouse model withdouble knockout (DKO) ofFarnesoid X Receptor (Fxr) andSmall Heterodimer Partner (Shp), theyfound that these mice are lean and resistant to diet induced obesity.

“To learn why the mice are lean we examined their caloric intake,activity and basal metabolism,” said Riessen. DKO mice ate the sameamount of food as the mice, which became obese but they were moreactive and burnt more fat. “Therefore we asked why are they moreactive?” said Akinrotimi. The answer was in skeletal muscle of thesemice, which had more type I, or slow twitch fibers, with high oxidationcapacity. “These mice were like marathon runners!” said Riessen.

Since the Anakk lab is focused on understanding liver diseases, they

clinical cholestasis, or very high levels of bile acidsin the liver, Anakk, with graduate student and firstauthor Bhoomika Mathur, observed the effect ofcholestasis on a key indicator of heart health.

“Healthy hearts metabolize fat as its mainenergy source to pump blood,” said Mathur.“Whereas, a stressed heart exposed to high levelsof bile acids, switches to glucose as its energysource, and this switch in fuel metabolism is seenduring heart disease.”

The researchers also discovered that increasedbile acids suppressed a master regulator ofmitochondrial function, Pgc1α, that is central forregulating fat breakdown. Thus, suppression ofthis key gene can result in reprogramming thesubstrate preference and heart failure. Theresearchers named this Bile acid mediated effecton the heart: “Cholecardia.”

Dr. Sayeepriyadarshini Anakk and Bhoomika Mathur

The Anakk Lab

examined why the DKO mousemodel did not develop fatty liverdisease despite eating high fatcontaining food. It is typicallythought that the receptor namedFxr (Farnesoid X Receptor) iscrucial to control the amount of fatin the liver. Fxr functions byrecruiting another receptor, Shp, todo its bidding. So when they foundthat really it was Shp that wasimportant to causing fatty liver itwas very surprising. “I didn’tbelieve it,” said Anakk. “I told them to do the experiment over and over

again.” The study showed that Shp has a role of its own. The paper washighlighted in an editorial by Dr. Richard Green from Northwestern,who suggests that “Targeting Shp may be efficacious for drugdevelopment to treat fatty liver disease.”

“Research is really exciting and takes a lot of hard work,” said Anakk.“But what makes this journey truly stimulating are the individuals whomake it happen. I have been very fortunate to have wonderfulundergraduate and graduate students in my laboratory who have mademy job easy, and it is to them I owe my success.”n

Oludemilade Akinrotimi,now a medical student atLoyola University StritchSchool of Medicine

Ryan Riessen, now a medicalstudent at Michigan StateUniversity’s College ofOsteopathic Medicine

Uncovering a Way to Fight Fatty Liver Disease

by Sayantani Sarkar and Dr. Sayee Anakk

MCB SCHOOL OF MOLECULAR AND CELLULAR BIOLOGY 2524

Academic DistinctionAbdul-Rahman Abdel-Reheem,

MCBHaijira Ahmed, MCB, Fall 2016Jessica Bachman, MCB, Fall 2016Abdul Bhuiya, MCB Honors

Conc.Larry Chen, MCB, Fall 2016Kevin Duffin, MCB, Fall 2016Brett Geever, MCB, Fall 2016Juhi Gupta, MCBΨMatthew Heffernan, MCBOctavio Herrera, MCBZhuoli Huang, BiochemistryMark Huston, MCBStephen Jan, MCBEun Ji Jeong, MCB Honors Conc.Linyang Ju, Fall 2016Amish Khan, MCB Honors

Conc., Fall 2016Tae Gyoon Kim, MCB Frank Leuzzi, MCBMatthew McKenna*Elan Melman-Volchenko, MCBTina Moazezi, MCBUdit Nangia, MCB Honors Conc.Christopher Nardone, MCBAkash Patel, MCBDavid Rhode, MCBAleetra Roberts, MCBDavid Rossi, MCBDiane Schnitkey, MCB Honors

Conc.Emma Schuster, BiochemistryChristine Shen, MCBMatthew Siegel, MCBRoss Skelly, MCB Honors Conc.*Lacey Solomon, MCBSteven Szymanski, MCBPha Thaprawat, MCB Honors

Conc.*Andy Wu, MCB Honors Conc.*Daniel Yoakum, MCBJohn Zahour, MCB

Highest Distinction,ResearchNicole Blum, MCB Honors Conc.Lolita Golemi, MCB, Fall 2016Zhouli Huang, BiochemistryJohn Krapf, MCB Honors Conc.Hayoon Lim, BiochemistryChristopher Nardone, MCBEmma Schuster, BiochemistryRoss Skelly, MCB Honors Conc.*Pha Thaprawat, MCB Honors

Conc.*Andy Wu, MCB Honors Conc.*

High Distinction,ResearchAbdul Bhuiya, MCB Honors

Conc.Kristopher Bosi, MCBCorinne Cannavale, MCBΨMacey Coppinger, MCB Honors

Conc.Mary Kate Feldner, MCBZachary Foust, MCB*Matthew Heffernan, MCBAllison Hollatz, MCB Honors

Conc.Nhan Huynh, MCB Honors

Conc., Fall 2016Eun Ji Jeong, MCB Honors Conc.Linyang Ju, MCB, Fall 2016Phillip Kim, BiochemistryJordan Kryza, MCBNicholas Lammer, BiochemistryVamsikrishna Naidu, MCBDiana Pacyga, MCBΨ

Weilun Pang, MCBKurt Reynolds, MCBNainika Roy, MCBKimberly Sam, MCB Honors

Conc.Diane Schnitkey, MCB Honors

Conc.Madeline Steiner, MCBBenjamin Wang, MCB

Distinction, ResearchAli Aijaz, MCBHumza Ashraf, BiochemistryKatrina Dovalovsky, MCB, Fall

2016Brandon Jones, MCBAmish Khan, MCB Honors

Conc., Fall 2016Giyeong Kim, BiochemistryXinyi Li, BiochemistryKatie Liang, MCBAlaa Mansour, MCB*Andrew McClintock,

BiochemistryOmar Shennib, Summer 2017Edward Wang, BiochemistryAlexander Willis, Biochemistry*Adam Wylder, Biochemistry

Molecular and CellularBiology HonorsConcentrationAbdul BhuiyaNicole BlumMacey CoppingerAllison HollatzNhan Huynh, Fall 2016Eun Ji JeongAmish Khan, Fall 2016John KrapfUdit NangiaKimberly Sam Diane SchnitkeyRoss Skelly*Pha Thaprawat*Andy Wu*

Biochemistry, SpecializedCurriculumHumza AshrafJesse BarrIvan ChauYiling Ding, Fall 2016Zhuoli Huang Giyeong KimPhilip KimAnastasia KondyukhNickolaus LammerHugo LeeXinyi Li Hayoon LimJiayi Luo Anita Mathew*Andrew McClintockRichard ParkZoe PetrosEmma SchusterMalvika SinghAleksas ValaitisEdward WangAlexander Willis*Adam Wylder

Molecular and CellularBiologyAlyssa AbayAbdul-Rahman Abdel-ReheemMalini AcharFarjad Adamjee, Fall 2016 Ariana AdelmanΨAnusha Adkoli

Hajira Ahmed, Fall 2016Hamza AhmedArjun AhujaAli AijazAbdul-Quddus AkinlusiWaleed AldadahIrfan AliLauren AndersenJohn Anderson, Summer 2017Gabriel Arce, Fall 2016Josephine Awah-Kanneh, Fall

2016ΨKayla BacharJessica Bachman, Fall 2016Eun Seol BaekSamiat BalogunMegan BartimocciaHannah BehleVanessa BelknapJohn BelzFranco Benyamin, Fall 2016Rohit BhonagiriJames BiondoSamuel BoctorPaul BogdanKristopher BosiDiamond BrownPaul BrownSaloni BuchPaul CamachoΨStefani CanadzicCorinne CannavaleΨAlejandro Cardona Arturo ChaidezCecilia Chan, Fall 2016*Audra ChavesMarialicia ChavezJohn Cheline, Fall 2016Larry Chen, Fall 2016Max ChenΨRachel ChinchillaMaham ChoudryGrace Clayton, Fall 2016Adam CohenJoshua CohrsHaven ComeauxKyle CootsAzariel CossElizabeth CullumNicole CurtisRyan CyriacΨFarnaz DadrassParoma De, Summer 2017Zachary DeanMatthew Del PinoSenem Demir, Summer 2017Taylor Desanto, Fall 2016Samantha DiCaroNathaniel Dimaano, Summer

2017Chuhong DingPatrick DoahHeidi Doden*Alexander Dolinar, Fall 2016Vinisha DoshiKatrina Dovalovsky, Fall 2016Kevin Drent, Fall 2016Kevin Duffin, Fall 2016Clarence DukesKevin DwyerNeil EdatSamantha EichnerCortney Eiers, Fall 2016Ehitare EmuzeJessica EndresJonathan EngAdam EsmailTristan EstepLauren Feld, Fall 2016Mary Kate FeldnerRyan FellMary Figura

Alejandra FloresSandra FolarinZachary Foust*Dulce FraustoSadie Freedman, Fall 2016ΨRachel FullLauren Gabra, Summer 2017Hannah GaddamTea GaribovicChristopher GaviganPalak Genge, Summer 2017Stephanie GeorgeMichael GiulianoMahima GoelLolita Golemi, Fall 2016Jose Gonzalez, Summer 2017Aleksandra GorskiJeffrey Gougis, Jr.Daniel GryzloΨQingrou Gu, Summer 2017Jovanny Guadarrama-Aniceto*Ellen GuoJuhi GuptaΨArmaan HaleemMohammed Hamad, Fall 2016Owen HauptMatthew HeffernanBrittany HermosilloOctavio HerreraHui Ting Iris HouSamantha HuntMark HustonHelena IgboAbdalah IsmailTeodora IvanovaJacek IwanickiChitra Iyer, Summer 2017ΨStephen Jan Adrianna JelenΨKun Jing, Fall 2016Varsha JohnΨErin Johnson, Fall 2016Brandon JonesLinyang Ju, Fall 2016Ayub JulanyChristian KalfasConstadina KalourisΨWei-Chun KaoAndriy KapeniakSarah KaschkeJohn KeeneElizabeth Kehl, Fall 2016Patrick KellyShivani KhakhkharNadia Khan, Fall 2016Sana KhanAkash KhuranaConnie KimKyung Il Kim, Summer 2017Lois KimSally Kim*Sang Min Kim Se Yi KimTae Gyoon KimMarit KirklysDavid KooJessica Kosapatti Rahul Koshy*Vladimir KoveshnikovSusmitha KowligyΨEmily KroegerJordan KryzaBenjamin LamarMaureen Lawless, Summer 2017Frank LeuzziJunyu LiRao Li Katie LiangJustin LienΨBailey LinkQingyuan LiuDi’Reon Lowry, Summer 2017

Lauren Lundquist, Fall 2016 Scott LyonsJad MaamariJared MaddenJennifer MainTheodore ManahanGio Manguerra, Summer 2017ΨAlaa Mansour*Hanna MatsesheKyle McClatcheyJanayah McClellanJasmine McDowellMatthew McKenna*Yuhao MeiElan Melman-VolchenkoDaniel MelnikovGibran Mendez, Fall 2016Stephanie MenezesMolly Mevis*ΨMaria MihailescuJeremy MikrutMichelle Miller, Fall 2016 Katherine MitchellTina MoazeziMitchell MohrAllison MonieRachel Moore*Grace MorrisseySamuel MounceRobert Mowery, Fall 2016Angelica Mulica, Fall 2016Vamsikrishna NaiduKimberly NalleySara NapoliChristopher NardoneEmilee NawaYusuf NekzadMichael NemsickElizabeth NettletonJoseph NeumannHeather NewmanGabriele Noreikaite, Fall 2016Margaret O'BrienQuincy OgboguChristine Oksas, Fall 2016ΨAmy Ou Diana PacygaΨBrandon PagniWeilun PangTara ParkYoonho ParkStephanie PascualAkash PatelDhruv PatelDil PatelΨJay PatelPayal PatelPriya PatelRavi PatelReema PatelShivaliben Patel, Fall 2016Shivam PatelΨThomas Pickett, Fall 2016Porsha PilateNathan PinskyKovas Polikaitis, Fall 2016Renee PondSarah RahmanNeha RaiJeffrey RajkumarAdin RandAlyssa ReitzDenise ReynishKurt ReynoldsMatthew RheeDavid RhodeAndrea Rice Noah RisnerJordyn Robare, Fall 2016Aleetra RobertsMegan RobinAbraham Rodriguez

Alexander Rodriguez, Fall 2016Daniel Rodriguez, Fall 2016Samuel RomoEvi Rondo, Fall 2016Anita Rong, Summer 2017Kathryn RossDavid RossiNainika Roy Daisy SalgadoSidra SalmanDonel SamuelDiana SarfoRyan SchaabChelsea Schultz, Summer 2017Minjoo Seo, Fall 2016Alexandria Shadid, Fall 2016Shane Shafi, Fall 2016Amy ShahBinoy Shah, Fall 2016ΨVaibhav SharmaToral ShastriChristine ShenOmar Shennib, Summer 2017Jinrong ShiMackenzie ShimminJulia SidorMatthew SiegelMatthew SimanonisΨMeghan SmithLacey SolomonMadeline SteinerMallory StimacNathaniel StringerMayu Sugikawa, Fall 2016 Zarin SultanaCindy SunKalee Sweeney, Fall 2016Shahbaz SyedSteven SzymanskiSabrina TahseenDaniel TanLawrence TanClaire TangBridget TesherZachary ThomasonChristopher ThuruthiyilDavid Tian*Thomas TopalisΨElizabeth Tran, Fall 2016Michael TrevinoΨTiffany Tsoi, Summer 2017ΨJoshua ValentinChristian VanhooserPravin VenceOkker Verhagen MetmanLauren WallingBenjamin WangAshley WehrheimKaitlyn WehrheimHailey Weidner, Fall 2016William WeissingerTheresa WelleΨKevin WellsJaleel WilliamsAlexander Willis*Julia WitowskaJulia WitvlietKui WuCharley XiXuling XuYiran Xu, Fall 2016Jason YehDaniel YoakumIvanna YuΨNeil Yu John ZahourChenqi Zhu

BiochemistryZehua BaoJonathan Chekan, Fall 2016Alexander CioffiJoshua Gajsiewicz, Fall 2016Michael Gregory, Fall 2016Daniel Harris, Jr., Fall 2016Gus LawrencePaween Mahinthichaichan, Fall 2016Kiruthika Selvadurai, Fall 2016Nitesh Shashikanth, Summer 2016Shannon WalshXin Ye, Fall 2016Xiaobin Zheng, Fall 2016

Biophysics & QuantitativeBiologyJavier Baylon Cardiel, Summer 2016Janish Desai, Fall 2016

Tyler Harpole, Summer 2016Seyfullah Kotil, Fall 2016Bo Liu, Summer 2016Stuart RoseKai Wen Teng, Fall 2016Erdal Toprak, Fall 2007Kevin WhitleyCharles Wilson

Cell and DevelopmentalBiologyYu Chen, Summer 2016Xiang Deng, Fall 2016Paul Hamilton, Summer 2016Anika JainJames KempRuiqi LiaoAmbika Nadkarni, Summer 2016Christina Rosenberger, Summer 2016

Amir Saberi, Summer 2016Younguk Sun, Summer 2016Rachel Waldemer-Streyer, Summer 2016Yating Wang, Summer 2017Hui-Chia Yu-Kemp, Fall 2016Xinying Zong

MicrobiologyMaksym BobrovskyyAriana Bravo-CruzWhitney England, Fall 2016He FuNicholas HessCrystal Hopp, Fall 2016Song Jiang, Summer 2016David Krause, Summer 2016Madeline López MuñozKenneth Ringwald, Fall 2016Margaret Wetzel, Fall 2016

Molecular and Integrative PhysiologyCongcong Chen, Fall 2016Kirsten EckstrumItamar LivnatJanelle MapesDaniel Ryerson

NeuroscienceAadeel Akhtar, Fall 2016Amogh BelagoduAlexandra BrooksPetra Majdak, Fall 2016George Nikolaidis, Summer 2016Matthew Petrucci, Summer 2016Jenessa SeymourBernard Slater, Fall 2016Benjamin Zimmerman, Fall 2016

Doctor of PhilosophyMaster of Science

Undergraduate Degrees—Bachelor of Sciences

M C B G R A D U AT E S

BiochemistryGulishana AdilijiangAaron Frimel, Fall 2016Carissa Klanseck

Biophysics & QuantitativelBiologySreeradha Biswas, Fall 2016

The lists are organized first by degree, then by major. Students earning the certificate in Microbiology are noted with *. Students earning the certificate in Neuroscience are noted with Ψ. MCB Learning Center for Teaching and Advising

Coming Soon in Fall 2018

• Learning Center with computer stations and tables forstudent group work and TA or Faculty office hours

• Six new active learning iFlex classrooms• New MCB Advising Center

• Seminar Rooms for Career Services Events• New space for limited-distraction exams• Meeting spaces available for student use• Space for Writer's Workshop Personnel

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26 MCB SCHOOL OF MOLECULAR AND CELLULAR BIOLOGY 27MCB