3Partners forDiscovery

4NewRecruits

5YoungInvestigators

6ResearchNotes

8Girls Scoutson Campus

I N S I D E T H I S I S S U E

Dean’s Discovery InitiativeSchool of Medicine Development OfficeVCU’s Medical College of Virginia CampusP.O. Box 980022 Richmond, VA 23298-0022

ADDRESS SERVICE REQUESTED

NONPROFIT ORGANIZATIONU.S. POSTAGE PAIDPERMIT NO. 869RICHMOND VA

V i r g i n i a C o m m o n w e a l t h U n i v e r s i t y

R E P O R T

D E A N ’ S

discovery

6ResearchNotes

SPR I NG 20 1 2 VOLUME 1 1 , NUMBER 1

by Frances Dumenci

“in the 20th century, the pharmaceutical industry researchedand developed new medications. Academic medical centers trained the scientistswho moved to pharmaceutical companies to do the translational research,”explains James Bennett, M.D., Ph.D., who holds the Bemiss Chair in theDepartment of Neurology. “In the 21st century, pharmaceutical companies arejust concentrating on development. The research has to come from universities.”

As many pharmaceutical companies cut back or eliminate their research divisions and concentrate solely ondeveloping drugs and bringing them to market, drugs are being discovered more and more by investigators atacademic medical research centers.

Each year, researchers at VCU create more than 100 inventions. A significant amount of that translationalresearch is taking place in the medical school, from studying more effective ways to treat patients following acardiac arrest to discovering new drug compounds for the treatment of various complex health issues, such asdegenerative brain diseases.

continued on page 2>

PATENTSPOTLIGHT

From DiscoverytoPatient Care

JAMES BENNETT, M.D., PH.D.,

IS A PHYSICIAN, RESEARCHER AND

THE CHAIR OF THE DEPARTMENT

OF NEUROLOGY. HE IS ALSO AN

INVENTOR ON PATENTS PROTECT-

ING THE USE OF A PROMISING NEW

DRUG COMPOUND.

{

Translationalresearch

aims to improve human health byconverting scientific discoveries intopractical applications as quickly and

efficiently as possible. Such discoveriestypically begin at “the bench” with basic

research in which scientists study disease ata molecular or cellular level, then progress tothe clinical level, or the patient’s “bedside.”

BENCHtoBEDSIDE:

Bennett personifies this shift in drug discovery from pharmaceutical companies to physicianscientists at academic medical centers. He is the founding director of the VCU Parkinson’s andMovement Disorders Center and an inventor on patents protecting the use of a new drugcompound that shows promise for treating the patients he sees in the clinic each day.

In 1996, Bennett identified the compound R(+) pramipexole as a candidate therapy foramyotrophic lateral sclerosis, or ALS. Sixteen years later, Bennett is awaiting results on a Phase 3trial that could lead to an FDA approval for patient with ALS later this year. (The timeline belowcharts the compound’s progress through regulators and clinical trials.)

Along the way, the compound has shown promise for treating other brain diseases likeAlzheimer’s and Parkinson’s. More clinical trials to test its usefulness against these diseases arenow underway.

“Because our research shows similar molecular abnormalities in ALS, Alzheimer’s andParkinson’s,” Bennett said, “I am hopeful that this compound will also slow developmentof degeneration in brains of individuals afflicted with these other diseases.”

_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _

VCU’s Center for Clinical and Translational Research fosters investigations that have thepotential to accelerate laboratory discoveries into treatments for patients. A $20 millionClinical and Translational Science Award from the National Institutes of Health fuelscampus research as well as nationwide collaborations with other academic medicalcenters working to advance science.

R E P O R T

D E A N ’ S

discovery

from bench to bedside :: behind the scenes

1 9 9 6James Bennett, M.D., Ph.D.,identified the compound R(+)pramipexole as a candidatetherapy for amyotrophiclateral sclerosis, or ALS. Hebegan running labexperiments.

2 0 0 0Bennett sent anInvestigational New Drugapplication to the FederalDrug Administration, whichwas eventually approved.

- - - - - - - -BACKGROUND: Federal lawrequires that a drug be thesubject of an approvedmarketing application before itis transported or distributedacross state lines. Because asponsor, in this case Bennett,probably will want to ship theinvestigational drug to clinicalinvestigators in many states, hemust seek an exemption fromthat legal requirement. TheInvestigational New Drugapplication is the means throughwhich the sponsor obtains thisexemption from the FDA.

2 0 0 1Bennett filed a preliminarypatent about his discovery.The US Patent Office issued afull patent to Bennett inJanuary 2007.

- - - - - - - -BACKGROUND: The Bayh-Dole Actwas enacted in 1980 to encouragethe development of universitydiscoveries that came aboutthrough federally fundedresearch. It allowed facultymembers and their universitiesto retain control of intellectualproperty and, as a result, sharea financial interest in thesuccess of a commerciallyvaluable discovery.

2 0 0 6Bennett licensed the drug toa start-up company, KnoppNeurosciences (now KnoppBiosciences).

- - - - - - - -BACKGROUND: Licensing providedKnopp the legal right to pursuecommercial development andalso determined how incomefrom drug development wouldbe distributed as royaltypayments.

2 0 0 7Knopp began designing andcarrying out clinical studiesat medical researchuniversities across thecountry to investigate thesafety and tolerability of thedrug, which was relabeled“dexpramipexole.”

- - - - - - - -BACKGROUND: “The first part oftesting a new drug for aparticular condition is safetyand tolerability,” explainsBennett. “Researchersinvestigate how patientstolerate the drug. Doses areescalated to see how peopledo. After this step, researchersdesign a larger study toexamine the drug’seffectiveness on disease.”

2 0 0 9Knopp completed the Phase 2study of the drug’s possibleeffectiveness and recentlyreleased the results in theprestigious scientific medicaljournal Nature Medicine.Knopp has licensed the drugto another company, Biogen-Idec, which will design andcomplete the Phase 3 studytrial.

WHERE WE ARE NOW: “The firstBiogen Phase 3 trial sought torecruit 800 subjects. When itclosed enrollment at the end ofAugust 2011, there were 950persons in the study,” Bennettsaid. “With this large numberof participants, Biogen will beable to determine fairly quicklyif the drug alters the course ofALS. If the Phase 2 results arerepeated in this larger study,the drug might be approved bythe FDA sometime later in2012.”

LAST FALL, a grassroots group of local Parkinson’s disease patientsknown as the Movers and Shakers celebrated hitting the goal in a $5 mil-lion campaign. Matched dollar-for-dollar with funding from the medicalschool, that private philanthropy was essential for creating the VCUParkinson's and Movement Disorders Center. Claudia M. Testa, M.D., Ph.D.,

points to the dedication of that volunteergroup as one of the reasons she’s now onthe medical school’s faculty.

“Part of the appeal of joining VCU is thatpeople in the local community had theenthusiasm and drive to build this greatnew center and made it happen,” she said.The fundraising campaign also supportsTesta’s work in a concrete way: it pro-duced the Joan Massey Endowed Chairthat Testa now holds.

An expert in movement disorders, Testa issetting up a clinic that offers comprehen-sive care integrated with clinical research.This includes a multidisciplinaryHuntington’s disease program. The clinicwill soon become an enrollment site fornational studies such as PREDICT-HD,which looks at the earliest changes inthinking skills, emotions and brainstructure that occur in people who areat risk for Huntington’s disease but areundiagnosed.

She is also collaborating on studies ofessential tremor with 14 other institutionsas part of a North America consortium she

founded. One of these studies aims to uncover the genetic variationsthat are associated with the onset of this common disorder. “We knowthat essential tremor tends to run infamilies but we don’t know much yet about its genetic basis,” Testa said.

Prior to joining the medical school last September, Testa was anassistant professor in the Department of Neurology and co-director ofthe Huntington’s Disease Center of Excellence at Emory University.

Testa says that receiving the Joan Massey Chair means she can devote thetime she needs to start up the new programs. “It covers part of my salaryand shows VCU is committed to seeing these programs grow and succeed.”

A RENOWNED PHYSICIAN-SCIENTIST, Steven R. Grossman,M.D., Ph.D., specializes in the treatment of gastrointestinal cancers andstudies the role of tumor suppressor proteins in cancer. One of hisresearch projects focuses on a protein called p53 that normally preventscells from becoming cancerous. But when p53 is inactivated by, forexample, a gene mutation, tumors are freed to grow. “We are investigat-ing how p53 works normally so we can find ways of restoring its functionin cancer cells,” Grossman said, adding that his goal is to eventuallydesign cancer therapies and prevention strategies based on thisresearch.

Another of Grossman’s objectives is to develop a drug that can inactivatea cancer-promoting protein known as CtBP. Grossman and his team mayhave found an answer in a compound called MTOB that can potentiallybe used to treat colon and pancreatic cancers. Currently they are testingthe compound in combination with standard chemotherapy in a mousemodel of human colon cancer. “We’re hopeful that we can move thisdrug or a similar one into human trials atthe Massey Cancer Center within the nexttwo years,” Grossman says.

Grossman joined the medical school lastJuly from the University of MassachusettsMedical School in Worcester, Mass. He holdsa grant from the National Institutes ofHealth and a prestigious Research ScholarAward from the American Cancer Society.

Grossman says that being offered theDianne Nunnally Hoppes Endowed Chair inCancer Research was a key factor in hisdecision to make the move. “Since it paysfor a significant portion of my salary, thatmeans that more of the money we receivefrom granting agencies can go towardsour laboratory research – for instance, forhiring postdoctoral fellows and buyingsupplies,” he explained. “Knowing thatthere is long-term, solid support for myresearch here was hugely important to me.”

Claudia M. Testa, M.D., Ph.D.,holds the Joan Massey Chair inthe VCU Parkinson’s andMovement Disorders Center,where she is also associatedirector of clinical care andresearch.

Program Director, VCUHuntington’s Disease Program

Associate Professor in theDepartment of Neurology

Steven R. Grossman, M.D., Ph.D.,holds the Dianne Nunnally HoppesEndowed Chair in Cancer Researchmade possible by members ofthe Moses D. Nunnally, Jr. family.

Chair of the Division ofHematology, Oncology andPalliative Care

Professor in the Department ofInternal Medicine with an affiliateappointment in the Department ofHuman and Molecular Genetics

PARTNERS FOR DISCOVERY[ ]Professors who hold endowed chairs can build promising research programs knowing they havean ongoing, stable source of funding. Meet two newly recruited faculty members whose work issupported by privately funded endowments. Both were drawn to join the medical school because

of its commitment to rapidly translating laboratory discoveries into treatments for patients.

by Jen Uscher

discoveryR E P O R T

D E A N ’ S

Ananda Amstadter, Ph.D., hasalways been interested in the interplay of

genes and environment, such as traumatic

events, for producing psychiatric conditions. A

clinical psychologist, Amstadter joined the

Virginia Institute for Psychiatric and Behavioral

Genetics at VCU to continue her studies of

mental health issues— including post-

traumatic stress disorder and substance abuse

— in soldiers returning from the wars in Iraq and

Afghanistan.

“I want to do nuanced assessments of different types of traumatic

events, look at risk and resiliency and personal history of trauma, and relate

that to mental health outcomes,” she said. A current project is investigating

how acute stress affects drinking behavior in soldiers with different degrees

of combat experience and mental health issues.

Amstadter earned her Ph.D. at Auburn University and did a clinical

internship at the Medical University of South Carolina. She stayed on in

Charleston as faculty until she came to the MCV Campus.

Amstadter says the draw was the institute, directed by Ken Kendler, M.D.

She lauds its richness of faculty and multidisciplinary environment. “The

field is so complex. Our institute has on facultypsychologists, psychiatrists,

statisticians, geneticists and molecular biologists. It’s a rare place.”

Joseph Landry, Ph.D.,came to the medical school with asolid background in the basicscience of epigenetics — how genesare regulated without altering theDNA itself. Now, as an assistantprofessor in human andmolecular genetics, he’s hoping toapply that knowledge to the real-world problem of breast cancer.

Using a mouse model of human breast cancer, Landry investigates howepigenetic processes may help cancerous tumors hide themselves from thebody’s immune defenses and how they may contribute to cancer’s spreadthrough metastasis.Landry earned his Ph.D. in genetics from Stony Brook University wherehe studied histones. He went on to a postdoctoral fellowship at the NationalInstitutes of Health where he studied chromatin remodeling. Both histonesand chromatin are structures that can control the accessibility of genes tobe expressed as proteins.With funding from the V Foundation for Cancer Research and theJeffress Foundation in hand, Landry was attracted to the MCV Campusbecause of its expertise in translational research. “I came to VCU for theopportunity to work with [department chair] Paul Fisher, to work with a lotof people who are well-versed in applying basic research findings todevelop therapeutics,” he said.

Leon Avery, Ph.D., has made acareer of studying how genes determinebehaviors. He joined the faculty last Augustas a professor of physiology and biophysicsto run his lab alongside a former student ofhis from the University of TexasSouthwestern Medical Center — Young-JaiYou, Ph.D., an assistant professor ofbiochemistry and molecular biology.

Avery studies feeding behavior inthe nematode worm Caenorhabditiselegans. “Worms have a simple nervous system of 302 neuronsand very good genetics,” he says, which makes them an ideal model withwhich to study how food and nutrition regulates behavior. Humans, incontrast, are a much more complicated system, but findings in the wormcan inform research in higher animals, he said. “What it does is gives you aplace to look.”

For instance, the molecule TGF-beta is involved in satiety, the signal thatsays “I’m full. Stop eating.” This molecule is important in human feeding aswell and may contribute to the wasting syndrome in some cancer patients.Avery finds the MCV Campus a good fit for the way he likes to do research.Its size and convenience allow him to spend more time at the lab bench.

Rebecca Etz, Ph.D., is a cultural anthropologist who recentlyjoined the family medicine department. That m

ay sound an odd match, but

it fits Etz perfectly. “In college, I always imagined I’d be a family doctor,” she

says. To learn more, she shadowed general practitioners, but found the

reality did not match her expectations. She gravitated to anthropology,

getting her Ph.D. at Rutgers.

Next, she took a postdoctoral fellowship at theRobert Wood Johnson

Medical School and did research, from the vantage point of an

anthropologist, on primary care practice. Fromthat experience, she

emerged with two driving motivations: cultural anthropology has a lot to

offer primary care practitioners, and current primary care practice does not

yet do enough to integrate mental and behavioral health. “For my career to

have meaning, I’d like to help figure out how to have medical records give

voice to patient concerns and to foster everyday integration of mental and

behavioral health into primary care practice,”said Etz.

Etz was excited to come to the MCV

Campus because of “the really incredibly

gifted team” in the department. “They

have an unusual level of passion and

enthusiasm for what they do,” she said.

Her current work involves finding

exemplars of primary care practice and

identifying key attributes—whether

innovative staffing or integrated care

delivery— from which others could learn

and grow.

newrecruitsby J I L L U . A D A M S

Talented Trend BustersIn the United States, educators have made only slow gains in recruiting minoritiesinto the fields of science, technology, engineering and mathematics. “Given theincidence of chronic disease in underrepresented populations, there is a need for moreunderrepresented people in research and in positions of leadership, so that they canensure that those health problems are adequately addressed,” said Suzanne Barbour,Ph.D., a professor of biochemistry and molecular biology.

Over the past few years, she has seen VCU move to the forefront in tackling thenational problem. The university currently boasts $1.3 million in grants supportingsix different programs that create opportunities for underrepresented minorities.

Four of those programs are funded through grants from the NIH’s Division ofTraining, Workforce Development and Diversity. That makes VCU one of only twoinstitutions in the country to reach that level of support, an achievement that Barbourcalled “a huge vote of confidence from the NIH.”

Barbour measures programs’ success by the nearly 200 talented trend busters who haveparticipated. The earliest of those now are securing positions in their chosen fields. Agraduate from the year-round training program for postdocs is on faculty at HowardUniversity’s medical school and, this May, the first two MARC Scholars will earntheir undergraduate degrees with plans to enter Ph.D. programs.

Read more about the programs at http://go.vcu.edu/trendbusters

Ph.D. candidate Allen Owens has benefitted from two of the medicalschool’s programs that are drawing underrepresented minorities intoscience careers. Because of his interest in how drugs interact with thebody– and a desire to learn about something completely differentfrom anything he’d already studied– he chose to study in theDepartment of Pharmacology and Toxicology for a year-long stint inthe Postbaccalaureate Research Education Program. There, he said, hewas pushed beyond his comfort level. “As an undergraduate, you learnabout science,” he explained. “But to be someone who developsscience is a different process.” With his interest in the world ofresearch confirmed, Owens now is pursuing a doctorate with thesupport of the IMSD program.

SUMMER PROGRAMS

HEROHealth Educational Research OpportunitiesSummer research program forunderrepresented undergraduates andprofessional students from any institution

STEP-UPShort-Term Education Program forUnderrepresented PersonsSummer research program for undergraduatesfrom any institution

YEAR-ROUND PROGRAMS

IMSDInitiative for Maximizing Student DiversityYear-round research training program forundergraduate freshman and sophomores andfirst and second year Ph.D. students from VCU

IRACDAInstitutional Research and AcademicCareer Development AwardYear-round research training program forpostdoctorals in training at VCU

MARCMinority Access to Research CareersYear-round research training program forundergraduate junior and senior honorsstudents from VCU

PREPPostbaccalaureate ResearchEducation ProgramYear-round research training program forrecent college graduates from any institution,but training at VCU

5

Record numbers of freshman have volunteered for a confidential study aimed at understanding how

genetic and environmental factors contribute to the development of alcohol use and emotional health.

“Having nearly 60 percent of VCU’s incoming freshman class participate in the Web-based survey is a huge

success, especially compared to an average of 34 percent Web-based survey completion at other

universities,” said Danielle M. Dick, Ph.D. She is co-investigator on the project with Kenneth S. Kendler, M.D.

The researchers were also impressed to see 97 percent of the freshman who completed the Web survey went

on to provide a saliva sample to take part in the DNA component of the study of the study.

Analysis of the DNA samples and survey data are underway. Researchers will do a follow-up survey this

spring, and each year thereafter while the students are at VCU. New freshman cohorts will also be enrolled

for the next several years. They will use the findings to gain insight into how genetics and environmental

factors influence the development of substance use and emotional health across the college years._ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _

Danielle M. Dick, Ph.D., associate professor of psychiatry, psychology and human

and molecular genetics; and Kenneth S. Kendler, M.D., the Rachel Brown Banks

Distinguished Professor of Psychiatry, professor of human and molecular genetics

and director of the Virginia Institute for Psychiatric and Behavioral Genetics

Sp

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RESEARCH NOTES

discoveryR E P O R T

D E A N ’ S

GRANTS SUPPORT HIV AND STD STUDIES IN CHINA

Hongjie Liu, Ph.D., associate professor of epidemiology

The spread of HIV and other sexually transmitteddiseases among older adults in China is driven, expertsbelieve, by female sex workers who are 35 years old orolder. China’s Ministry of Health would like to launchinterventions aimed at this group, but the lack ofepidemiologic data from community-based studies hasbeen a challenge.

Now a $1.56 million grant from the National Institutes of Health will supportLiu’s study of the epidemic as well as personal and social determinants thatinfluence risky behavior. “This is the first large-scale, multi-site studyexamining the extent of how HIV and STDs spread in this unique andstigmatized population in China,” said Liu, who is principal investigator thefour-year international project that includes the University of California, LosAngeles; Johns Hopkins University; and China’s Shandong University andNanning Center for Disease Control and Prevention.

In another study, Liu is partnering with colleagues at Vanderbilt Universityand the Chinese government to reduce the spread of HIV infection amonggay men. Supported by a $2-million NIH grant, the five-year project will betechnology driven, using text messaging to deliver intervention tips.

PREVENTING COLLATERAL DAMAGEAFTER HEART ATTACK

Antonio Abbate, M.D., assistant professor of medicine in theDepartment of Internal Medicine’s Division of Cardiology

During a heart attack, cardiac tissue is deprived of oxygenand nutrients and the resultant injury is met with aninflammatory response. However, inflammation is adouble-edged sword, triggering both healing processes andfurther damage. In a paper published in the Dec. 6 issue ofthe Proceedings of the National Academy of Sciences,

Abbate and his colleagues report on a particular inflammatory mediator thatorchestrates the damage side of the equation.

In an animal model, blocking this mediator — interleukin-1 beta (IL-1β) —prevented adverse outcomes such as heart enlargement. “Based on the findingsof the current study we are even more convinced that blocking IL-1βmay besafe and beneficial, and we are now exploring novel ways to do so,” he said.Abbate’s research team included Internal Medicine’s Fadi Salloum, Ph.D., andStefano Toldo, Ph.D., as well as the School of Pharmacy’s EleonoraMezzaroma, Ph.D., and Benjamin VanTassell, Pharm.D. Clinical trials at theVCU Pauley Heart Center are now testing an IL-1β blocker called anakinra inpatients with various heart conditions.

OUTMANEUVERING CANCER’S EVASIVENESS

Masoud Manjili, D.V.M., Ph.D., assistant professor ofmicrobiology and immunology and Massey CancerCenter member

Growing cancers develop ways to evade the body’s ownimmune attacks and those same mechanisms can subvertcancer immunotherapy. Manjili has been working toovercome this problem. In a paper published in the July15, 2011, issue of the Journal of Immunology, Manjili

and his colleagues described a method to improve adoptive cellular therapy,the current approach to using a patient’s own immune cells to fight tumorgrowth in breast cancer. Manjili’s group found that re-programming T cellsand natural killer T cells by activating and changing their phenotype wouldresult in the rejection of breast tumor cells when these T and natural killerT cells were transfused in an animal model.

“We’re very encouraged by our results and hope this approach will result inmore effective adoptive cellular therapies against breast and other cancers,including melanoma, prostate and ovarian cancer,” Manjili said. Working withVCUTech Transfer, he and his colleagues filed a patent on the technology.They have received additional grant funding to determine whether thisprotocol may re-program cells of the immune systems of breast cancer patients.Results are expected to lead to breast cancer immunotherapy clinical trials.

CONSORTIUM STUDIES POST-CARDIAC ARREST PATIENTS

Mary Ann Peberdy, M.D., professor of internal medicineand emergency medicine

To improve care for patients who suffer a cardiac arrest,members of the Pauley Heart Center and Department ofEmergency Medicine will lead a four-member consortiumthat includes the internationally renowned Beth Israel-Deaconess/Harvard University, the University ofPittsburgh and the University of Pennsylvania.

“Most large, single institutions treat approximately 10 to 12 patients a year.As the regional referral center for cardiac arrest treatment and Level I TraumaCenter, VCU Medical Center treats about 70 or 80 post-arrest patientsannually,” said Peberdy, who is the lead investigator of the multi-center study.“The three other consortium members are similar to us in terms of treatmentsand patient volumes.”

The consortium is funded by the National Institutes of Health as part of the$20-million Clinical and Translational Research Award that seeks to fosterpartnerships that speed innovation and accelerate laboratory discoveries intotreatments for patients.

NEW TARGET IN BRAIN CANCER

Paul B. Fisher, M.Ph., Ph.D., professor and chair of humanand molecular genetics and the Thelma Newmeyer CormanEndowed Chair in Oncology Research

Brain cancer causes altered neuronal signaling anddegeneration of nerve cells. New research by Fisher detailsthe precise mechanism by which this damaging cascade ofevents occurs and reveals new targets with which to treatbrain cancer — and potentially other neurodegenerative

diseases, such as Alzheimer’s, Lou Gehrig’s (Amotrophic Lateral Sclerosis),Huntington's and Parkinson’s.

The most common and aggressive form of brain cancer, known asglioblastoma multiforme, contains the AEG-1 oncogene that decreases theactivity of a common neurotransporter involved in glutamate transport, amolecule which can be toxic to neurons when at high concentrations. “Inhighlighting the importance of AEG-1 in brain cancer development,progression and neurodegeneration, we have identified a new target forinhibiting all of these processes through therapeutic intervention,” Fisher saidof the study, which was published in the Oct. 15, 2011, issue of CancerResearch.

Fisher also is co-program leader of Cancer Molecular Genetics at the MasseyCancer Center and director of the VCU Institute of Molecular Medicine. Hewas recently named co-editor-in-chief of the premier Elsevier cancer researchreview journal Advances in Cancer Research.

ACCUMULATED EXPERIENCES ARE HUGEFACTOR IN ANXIETY AND DEPRESSION

Kenneth Kendler, M.D., the Rachel Brown BanksDistinguished Professor of Psychiatry, professor of humanand molecular genetics and director of VCU’s VirginiaInstitute for Psychiatric and Behavioral Genetics

Twin studies can be enormously helpful when trying tosort out genetic influences from environmental ones.Kendler recently studied anxiety and depression inthousands of identical twins using established databases.

He and his colleagues found that environmental factors — namely, lifeexperiences — played a large role in how much anxiety and depressionsomeone has as an adult. “In this time of emphasis on genes for this and thattrait, it is important to remember that our environmental experiences alsomake important contributions to who we are as people,” he said of the study,published in the October 2011 issue of Psychological Science.

In a second study last year, Kendler participated in an international effort toidentify novel genes that contribute to schizophrenia and bipolar disorder. Fivenew gene variants were described and published by the team in the Sept. 18,2011, issue of Nature Genetics.

SINGLE GENE ASSOCIATED WITHAUTISM SPECTRUM DISORDER

Sarah H. Elsea, Ph.D., associate professor in theDepartments of Pediatrics and Human and MolecularGenetics

A neurodevelopmental syndrome that includes autismspectrum disorder with intellectual disability, languageimpairment and seizures appears to result from tinychanges in a single gene, according to a recent study. Inan article published in the Oct. 7, 2011 issue of the

American Journal of Human Genetics, Elsea and her international team ofcollaborators describe genetic alterations in a critical region of chromosome 2.The alterations or small deletions, identified in 65 patients, all affected a singlegene, called MBD5. Further studies of large autism cohorts revealed thatvariants in the MBD5 gene are a likely causative factor in about one percent ofautism cases.

Future work will focus on understanding the developmental and cognitiveeffects associated with these genetic changes. “We expect these findings topush diagnostic laboratories to modify the way they assess genes in thediagnosis of neurodevelopmental disorders, which will improve diagnosis andinform parents regarding familial risk for autism spectrum disorder,” she said.With proper diagnosis, targeted interventions can be started early, which mayimprove outcomes.

MOLECULAR DETAILS OF ANTIPSYCHOTIC DRUG ACTION

Diomedes E. Logothetis, Ph.D., the Bower Chair of theDepartment of Physiology and Biophysics

Antipsychotic drugs are classified as typical if, likehaloperidol, they target dopamine receptors. Those, suchas risperidone, that target serotonin receptors are classifiedas atypical and command a market of $10 billion peryear. The most effective antipsychotic for more than 50years has been clozapine, which targets both: serotonin

receptors at lower concentrations and dopamine receptors at higher. But evendrugs of choice show significant undesirable effects and only treat 70 percentof patients. As a result, the need for new, more effective drugs is great.

Yet the precise mechanism of antipsychotic drugs has been hard to pinpoint,thus making it hard to design new compounds. An internationally recognizedleader in the study of ion channels and cell signaling mechanisms, Logothetisreports in the Nov. 23 issue of Cell that atypical antipsychotics act on areceptor complex containing serotonin and glutamate receptors. “Not onlyhave we learned how antipsychotics drugs are effective, but we have also foundthat the signaling through this receptor complex is critical to how theseantipsychotics work,” he said. Moreover, Logothetis and his team, whichincludes researchers from the Mount Sinai School of Medicine in New Yorkand the University of Maryland, have developed a promising test foridentifying compounds that interact with the receptor complex in the sameway, paving the way for high-throughput screening for novel compounds.

IMPROVING HEALTH THROUGH SOCIETAL CHANGE

Steven Woolf, M.D., M.P.H., professor of family medicineand director of the VCU Center on Human Needs

“As we see poverty rates climbing and know thateconomic conditions have health implications, we canpredict an actual tidal wave of disease coming to thehealth care system,” Woolf said.

He points to non-health factors like education andeconomic conditions as major drivers of health outcomes

– and of health care spending. His message is drawing attention, from acommentary in last May’s Journal of the American Medical Association to arecent webinar that drew nearly 150 participants, including governmentofficials and senate and congressional staffers. The webinar introduced a newpublication series from the Center that will analyze national and state-leveldata to reveal how Americans are faring when it comes to basic needs.

The Center is supported by grants from the W.K. Kellogg Foundation, theRobert Wood Johnson Foundation and the National Institutes of Health.

TACKLING THE MITOCHONDRIAL GENOME

Shirley M. Taylor, Ph.D., associate professor of microbiolo-gy and immunology and Massey Cancer Center member

In addition to the main genome contained in the nucleus,cells carry a second set of genetic information in themitochondria — the power-generators of the cell. Now, anew discovery by Taylor reveals that the on-off switch forgene expression that exists in the nucleus is also found inthe mitochondrial genome.

Certain segments of DNA strands can be chemically modified, therebysilencing a gene. Taylor’s group showed that these same modifications exist onmitochondrial DNA and demonstrated that the enzyme responsible for thesemodifications is located within these power generators. The discovery hasimplications for diseases such as cancer, heart disease, diabetes and Parkinson’sdisease. “Our research indicates that errors in gene expression in mitochondriacontribute to the loss of mitochondrial function that is typical of cancer and ahost of other age-related diseases,” she said. The work was published in theMarch 1, 2011, issue of the Proceedings of the National Academy of Sciencesand led directly to a three-year grant from the National Science Foundationaimed at understanding the significance of mitochondrial DNA modificationto mitochondrial energy generation.

PM&R ASSOCIATE PROFESSOR LAUDED FORTWO EARLY CAREER ACHIEVEMENTS

Juan Carlos Arango-Lasprilla, Ph.D., associate professor ofphysical medicine and rehabilitation

In the 10 years since he received his doctorate, Arango hasdistinguished himself through substantial contributionsto the field of brain injury. He has been instrumental insecuring over $3 million dollars in grant funds primarilyfocusing on research with culturally diverse populationsand has published more than 130 articles and book

chapters in the area of brain injury, cultural issues and rehabilitation. He hasconducted numerous research studies in Europe, Central America, SouthAmerica and the U.S. to understand and address the psychological andemotional needs of individuals with brain injury and their families.

In November 2011, Arango received the Early Career Award from theNational Academy of Neuropsychology at the academy’s annual conference,and in March 2012, he was recognized with the 2012 International BrainInjury Young Investigator Award at the Ninth World Congress of Brain Injuryin Edinburgh, Scotland.

TWO NEW AVENUES FOR FIGHTING MULTIPLE MYELOMA

Steven Grant, M.D., professor of internal medicine and theShirley Carter Olsson and Sture Gordon Olsson Chair inOncology Research

Late last year, Grant made two contributions to researchon multiple myeloma, a cancer of white blood cellsoriginating in the bone marrow. In a study published inthe Nov. 10 issue of Blood, Grant and colleagues tested anew treatment regimen on a subpopulation of myeloma

cells that has traditionally been hard to target. Cells that aren’t dividing (i.e.,quiescent cells) are generally resistant to many inhibitors of tumor growth.However, Grant's team used a combination strategy that simultaneouslydisrupted survival and DNA repair pathways, and effectively killed these cells.Importantly, the treatment did not harm normal bone marrow cells, and plansfor a clinical trial based on this concept are underway.

In a second study, published in the Journal of Biological Chemistry on Sept.30, 2011, Grant and his team describe another way multiple myeloma cellsbecome resistant to treatment. They show that blocking the activation of aprotein complex known as NF-kappaB made cells considerably morevulnerable to a class of anti-cancer drugs known as histone deacetylaseinhibitors.

Grant, who is also associate director for translational research and program co-leader of Developmental Therapeutics at the Massey Cancer Center, recentlyreceived several new appointments that will broaden his influence off-campus,including one to the Investigational Drug Steering Committee of the NationalCancer Institute.

rianna Winston thinks DNA is cool. DaniellaHamilton likes marine biology. Emma Krusz isconsidering a career as a pharmacist or anurse practitioner.

No matter what choice they make, these youngbudding scientists now have a greater understandingof the connection between science and their careeroptions thanks to the sixth annual “Girls ScoutsScience Day” presented by the Women in Sciencestudent organization.

Every March, more than 100 Girl Scoutsarrive on the MCV Campus to experiencea half-day of workshops, lectures andhands-on experiments led by professorsfrom the MCV and Monroe Parkcampuses. This year they represented21 troops from around central Virginiaand were accompanied by 40 leadersand parent volunteers.

“It’s wonderful that VCU makes these opportunitiesavailable,” said Mary-Lynn Krusz, Emma’s mother andtroop leader from Tappahannock. “I think science,technology, engineering and mathematics are soimportant for the girls to be exposed to. These arenot traditional female careers and I don’t know of aprogram like this where they might get thisexperience. It’s not something they get in theclassroom.”

The Scouts, ages 9 – 12, spent time in small groupswhere they were exposed to various biochemical andmolecular research techniques, robotics, simulationand even a mock crime scene to demonstrate thestudy of forensic science.

“Forensic science is a great hook to get young peopleinterested in science and math,” said Michelle Peace,Ph.D., interim chair of the Department of ForensicScience in the College of Humanities and Sciences.“Because of that, we’re always really eager to inspireand engage young people at this level. So when wewere asked to participate again this year, I said, ‘Ohmy heaven’s yes!’”

Women in Science member and event organizerDivya Padmanabha, a graduate student inBiochemistry and Molecular Biology, has fondmemories of being a Girl Scout herself in India. “As astudent troop leader, I developed valuable skills that

help me even today. I believe that my decision toenter graduate school was shaped by my experiencesas a young girl. I hope that the hands-on experiencesin labs and conversations with scientists at VCU willinspire the young girls to take on exciting challengesthat science and engineering have to offer. I hopethat, like me, some girl will discover herself throughthe marvels of science!”

For Frederica Winston, a parent volunteer with Troop894 in Hanover County, the experience providedsomething for everyone. “Every girl had anopportunity to learn something about the variousareas of science,” she said. “I was impressed with thevariety of activities and the individualizedinformation.”

For Jan F. Chlebowski, Ph.D., professor in theDepartment of Biochemistry and Molecular Biologyand associate dean for Graduate Education in themedical school, the annual event is a labor of love.Not only for himself, but for his colleagues as well.

“Every year has been great. The people who run thedemonstrations and the workshops deserve alot of credit,” he said. “They comeup with demonstrationsthat areappealing, andthey devote a lotof time to theevent. We’ve had notrouble gettingpeople to participate.It really speaks well for thewhole VCU community.”

Thanks to the Women inScience studentorganization and theannual “Girl ScoutsScience Day,” there’s anew cadre of future femalescientists in Central Virginiawho can explain the origin ofa fingerprint while building DNA structures fromTwizzlers, gumdrops and toothpicks.

THE GIRL SCOUTS HAD THE CHANCE TO EXAMINE A

MOCK CRIME SCENE AS WELL AS USE TWIZZLERS,

GUMDROPS AND TOOTHPICKS TO BUILD THE DOUBLE

HELIX STRUCTURE OF DNA.B

DEAN’S DISCOVERY REPORT | Volume 11, Number 1

The Dean’s Discovery Report is published twice a year by Virginia Commonwealth University’sSchool of Medicine on the Medical College of Virginia Campus. Reader comments and suggestionsare welcome; please call (800) 332-8813 or (804) 828-4800, e-mail MedAlum@vcu.edu or write toP.O. Box 980022, Richmond, VA 23298-0022.

The Dean’s Discovery Initiative provides an opportunity for donors to transform the researchenvironment in the School of Medicine. Through philanthropy, alumni and friends can supportthe school's research endeavor in ways that traditional funding sources do not.

Dean: Jerome F. Strauss III, M.D., Ph.D.Produced by the School of Medicine’s Alumni and Development Office: Associate Dean forDevelopment, Tom Holland; Editor, Erin Lucero.ContributingWriter: Jill U. Adams, Nan Johnson, Jen UscherPhotographers: Allen Jones, Tom Kojcsich, Jay Paul and VCU Creative ServicesGraphic Design: Zeigler|Dacus

© Virginia Commonwealth University, 2012.

Serving the Medical College of VirginiaCampus of Virginia CommonwealthUniversity since 1949 and proud to be apartner with the School of Medicine.

PO Box 980234Richmond, VA 23298

(804) 828-9734www.mcvfoundation.org

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