M.D.-Ph.D. ProgramH A R V A R D M E D I C A L S C H O O L

Volume 13, No. 2 Fall/Winter 2002

Students, faculty and staff gather at the 20th Annual M.D.-Ph.D. Retreat in Waterville Valley, NH.

Sun Reflects on20th Annual Retreat

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by Bryan K-H. Sun

There’s an energetic buzz in the car— somemixture of Friday afternoon relief, theexcitement of getting out of town, and theanticipation of the weekend retreat.

I’m driving up I-93 with ShannonMcDonald (Year 3-Math), John Ng (Year 5-Biophysics), Rebecca Spencer (Year 6-BBS),and Tammy Chang (Year 9-Immunology).Wading through rush-hour traffic, weexchange tales of lab and the wards, updateeach other on who’s-going-into-what-residency and who-matched-where and who-joined-which-lab, ask each other aboutresearch progress, and argue whetherEminem is a genius or a fake. A back-of-the-napkin calculation tells us that we might justmake it in time for dinner. The tollbooth looms,and exact change appears from collectivepockets.

Twenty years ago, in a cool Octoberjust like this, the first M.D.-Ph.D. retreat washeld at the Cape Cod Sea Camps, wherestudents and faculty shared chilly cabins onthe beach and cafeteria food about one mile’swalk inland. Since then, the retreat locationhas migrated to several other locationsincluding the MBL at Woods Hole, and onone occasion, Linda Burnley’s house.Waterville Valley has been the retreatdestination for the last five years. Whilehaving less rugged charm than the originalretreat, it still aims to bring together facultyand students to share ideas about science,medicine, and careers.

We’ve made it. Well fed from dinner(with minutes to spare!) we head into thefirst set of talks that evening. As usual,there’s a wide breadth of research areas and

Every Dog Has His Day: Update onM.D.-Ph.D. Alumnus Lewis A. Chodosh

continued on page 2

by Andrew E. Elia

Lewis Chodosh graduated from the HarvardM.D.-Ph.D. Program in 1989. He is currentlyAssociate Professor in the Departments ofCancer Biology, Cell and DevelopmentalBiology, and Medicine at the University ofPennsylvania. Many readers of the M.D.-Ph.D. Newsletter, at least those who havereached the six-year mark like myself, mayremember him as author of the articles, “MyLife as a Dog” and “My Life as a RapidlyAging Dog,” published during 1993-1997.Through fictitious diary entries, theychronicle the painful existence of M.D.-Ph.D.graduate Jack Dunbal (aka Lewis Chodosh)from internship through the early years of

his fast-moving assistant professorship. Ihad the opportunity to interview Dr.Chodosh recently and asked him whetherthe pace of academic life has begun toplateau after receiving tenure.

“No,” answered Dr. Chodosh.“It’s accelerating and it’s horrifying. It’s notunlike the expanding universe. You think itshould be slowing down but it’s actuallyspeeding up.” Dr. Chodosh heads a breastcancer research laboratory of 22 people andattends on the endocrinology service at theHospital of the University of Pennsylvaniaone month per year. It is no wonderthat his work has maintained a

2 Harvard M.D.-Ph.D. Program Newsletter Fall/Winter 2002

Lewis A. Chodosh, 1989 M.D.-Ph.D. Graduate

Every Dog, from page 1

Andrew E. Elia is a seventh year M.D.-Ph.D.

Program student (HST, DMS, BBS-Cell Biology).

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frightening pace.Dr. Chodosh earned his Ph.D. in

the laboratory of Dr. Phillip Sharp at MIT,where he was among the first to performDNA gel shift assays in mammalian cells,allowing him to identify some of the earliestpromoter-specific mammalian transcriptionfactors. His work, published in threeseparate Cell papers and a Science paper,was instrumental in establishing theeventually sprawling field of transcriptionfactor biology. When he began identifyingthese DNA binding proteins, he remembersDr. Sharp (whose picture hangs in Dr.Chodosh’s office) speculating, “There maybe many more of these promoter-specifictranscription factors than we thought. Theremay be as many as … TEN of these things.”Of course, hundreds are now known.

After a residency in medicine anda fellowship in endocrinology at MGH, Dr.Chodosh joined Dr. Philip Leder’s lab atHarvard Medical School. “In the Leder lab,”explained Dr. Chodosh, “I became interestedin what I would call experiments of natureand, more specifically, how nature preventsbreast cancer.” Through Dr. Leder’s urging,Dr. Chodosh focused on the observationthat women who have a child early in lifehave a significantly lower lifetime risk ofdeveloping breast cancer. This reduced risklikely stems from protective physiologicevents that occur during full maturation ofthe mammary gland during pregnancy andlactation.

Cancer susceptibility, explains Dr.Chodosh, depends on the developmentalstage of the gland at the time of theoncogenic insult. To study this relationship,the Chodosh lab designed a doxycycline-inducible transgenic mouse system, whichhas allowed them to activate oncogenes inmammary glands at various developmentaltime points, during which they could thenexamine cancer susceptibility. These studies

are made possible by tight temporal controlwithin their system, which provides over100,000-fold induction of transgenes uponadministration of doxycycline, resulting inclear glandular changes in 24 hours.

Working with mouse modelsinducibly overexpressing the MYC andNeu oncogenes, the Chodosh lab has madeimportant findings, published in Nature

Medicine and Cancer Cell, about lategenetic events contributing to breastcancer progression. Though not havingset out to study advanced stages ofcarcinogenesis, they found that after de-induction of either MYC or Neu, completeregression of most oncogene-inducedtumors occurred. In the case of Neu-initiated primary mammary tumors, lungmetastases were also reversible. Suchtumor reversibility, initially shown inmelanomas by Dr. Ronald DePinho, isexciting because it lends credence to theidea of treating cancer with pathway-specific drugs after tumors have alreadydeveloped.

Even more exciting was Dr.Chodosh’s finding that of those tumorsfailing to regress after MYC de-induction,most had spontaneously acquiredactivating point mutations in the oncogeneKras2, yet not in its closely related familymember Hras1. “This provides strongevidence,” says Dr. Chodosh “that tumorsescape dependence on an initiatingoncogene by preferred secondarypathways.” Their finding has importantclinical implications because single drugsare almost never sufficient for curingcancer. If tumors become resistant to drugsby preferred secondary mutations that areknown, one can potentially prevent tumorrecurrence by simultaneously targetingthese secondary pathways during initialtreatment.

More recently, Dr. Chodosh hasbegun using DNA microarrays to studymechanisms of mammary oncogenesis.Such genomic studies have plunged hislab into the field of computational biology,which Dr. Chodosh says “keeps him young… or at least off street corners.” Using

microarrays, the Chodosh lab has identifiedgenes whose expression in the breast ispermanently altered after an early first full-term pregnancy. Experiments are currentlyunderway to study these genes as potentialmediators for parity-induced protectionagainst breast cancer.

Dr. Chodosh has continued seeingpatients while maintaining an active researchlab and hopes to see his career involve evenmore clinical work in the future. For example,he would love to study how parity affectsendocrine function in humans and ultimatelyto perform clinical trials on hormonalchemoprevention regimens aimed atmimicking the protective effects of parity onbreast cancer risk. Making the decision topursue a career in both science and medicine,however, means that you “have to give somestuff up,” says Dr. Chodosh. “People willalways be comparing you to others who doeither science or medicine full time,” heexplains. “You make some sacrifices for doingwhat you love.”

When I asked Dr. Chodosh aboutwhether he had any advice to offer M.D.-Ph.D. students, who were not so far along intheir careers yet still rapidly aging, he replied,“Follow your heart, and don’t worry aboutthe time.”

“I became interested in

what I would call experiments of

nature and, more specifically, how

nature prevents breast cancer.”

3Harvard M.D.-Ph.D. Program Newsletter Fall/Winter 2002

by John W. Hanna and Mauro D. Zappaterra

This past summer, the first and second yearclasses continued what has become atradition at HMS: the M.D.-Ph.D. summerjournal club. There was a particular emphasisthis summer on studying papers that utilizednovel or paradigmatic approaches ortechniques. In particular, a number of thepapers studied this summer in the journalclub were breakthrough papers, that ispapers that resolved longstanding problemsor that launched whole new fields ofinvestigation: true “citation classics.” Thegoal was to use the journal club to discusssome of the different ways of approachingscientific problems utilized in the varioussubfields of biomedical science. The hopeis that students will then take these newapproaches back to their own labs, and applythem, perhaps in novel ways, to their ownresearch problems.

The journal club kicked off with adiscussion of what has been called the most

beautiful experiment in biology, Meselsonand Stahl’s demonstration of the semi-conservative nature of DNA replication. Inthe following weeks, a wide variety ofpapers were discussed. Work on proteintransport, from the laboratory of JimRothman, this year’s co-recipient of theLasker Prize, highlighted the power ofbiochemical reconstitution in the study ofcell biological processes. Molecular biologywas the subject of discussion as weexamined the work which providedexperimental support for the now famousball-and-chain mechanism of inactivation ofcertain potassium ion channels. Twosuccessive lively discussions were held onthe issue of stem cell research, with oneweek devoted to the potential of stem cellresearch for therapeutic medicine and theother week serving as a caveat for thosewho would rush into stem cell therapies.Continuing with the theme of therapy, we

Journal Club Studies the Classics

discussed rational drug design, focusing onwork towards the development of anti-HIVdrugs, from the laboratory of Peter Kim.

The summer journal club was asuccess in many respects. Attendance washigh with approximately half of the combinedfirst and second year classes attending eachmeeting. More importantly, the discussionswere lively, and in true M.D.-Ph.D. form,highly didactic. Given the success of thissummer’s venture, the first and second yearclasses will attempt to carry on the journalclub into the school year. The hope is thatthis endeavor will further allow students tomaintain ties to basic science during the firsttwo years of medical school. Journal clubwill meet on the last Wednesday of eachmonth, in MEC L-OO7 at 7:15 P.M. All M.D.-Ph.D. students are encouraged to attend.

John W. Hanna and Mauro D. Zappaterra are

second year M.D.-Ph.D. Program students.

Where are they now?

30th Anniversary of MARC &MBRS Programs CelebratedThe Annual Biomedical Research Conference for MinorityStudents was held November 13-17, 2002 in New Orleans,Louisiana. This year marked the 30th anniversary of theMinority Access to Research Careers (MARC) and MinorityBiomedical Research Support (MBRS) programs. Over 2500students gathered for the conference, which represented thelargest gathering of research orientated minorityundergraduates in the country.

Representatives from Harvard included Linda Burnley(M.D.-Ph.D. Program), Dr. Jocelyn Spragg (Division of MedicalSciences), Dr. James Hogle (chair of the program in biophysics),Michele Jakoulov (administrative coordinator, biophysics),Victoria Love (immunology graduate student) and Jason Sello(postdoctoral research fellow in Biological Chemistry andMolecular Pharmacology, and graduate of the biophysicsprogram).

Juan Carmona, a Summer Honors UndergraduateResearch Program (SHURP) student, also won the top awardin the cellular biology category for his poster, “Cell-surfaceInteraction of Transferrin Receptor 1 with the T-cell Receptorand CD3 Signaling Complex in T-lymphocyte Development.”The poster reflected the research he did over the summer inthe lab of Dr. Nancy Andrews, the M.D.-Ph.D. Program Director.

Harvard M.D.-Ph.D. Program Alumni (n=310)

by years of graduation

1975-1990 1991-2002(n=117) (n=193)

Professor 15% 0%Associate Professor 33% 2%Assistant Professor 27% 21%Instructor 0% 8%Clinical/Research Fellows 0% 57%Government 7% 0%Industry 12% 6%Other* 6% 6%

Total 100% 100%

*includes 19 in private practice, 6 unknown and 1 deceased

Source: Linda Burnley

4 Harvard M.D.-Ph.D. Program Newsletter Fall/Winter 2002

The Annual Retreat Lobster BakeTop photo: Dr. David Golan & Finny Kuruvilla.Bottom photo: (Back L-R) Andy Aguirre,Sashank Reddy and Cullen Taniguchi.(Front L-R) Rebecca Spencer, Sahar Nissim,Francis Alenghat, Jason Comander,Rita Khodosh and Onyinye Iweala.

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SAVE THE DATE!

April 24-27, 2003

M.D.-Ph.D. ProgramRevisit Weekend

for applicants offered admission

approaches among the studentpresentations, from Anna Greka’s (Year 5-Neuroscience) studies on ion channels andneuronal differentiation to Yonatan Grad’s(Year 6-BBS) computational approach toidentifying micro-RNAs to Thanh NgaTran’s (Year 7-MIT Chemical Engineering)designs of an electrically-switchable surfacemonolayer.

The next morning’s student talkscontinue to showcase even more diversestudent research. I’m introduced to someunique animal experiments which include,to a first approximation, chilling mice in thecold room and observing ferrets as theywatch television. In practice, James Rhee’s(Year 6-BBS) research on mouse PGC-1a andHNF4a during fasting provides a neatmolecular explanation for a metabolicadaptive response. Sohail Tavazoie’s (Year8-Neuroscience) studies of a ferret’s thalamicresponse to horizontal stimuli indicate thatretinal-thalamic connections are dynamicand changeable during development. Theapparent madness to the methods yieldsfruitful discoveries.

Dr. David Nathan, the keynotespeaker, presents a broad view of clinicalresearch from his personal and professionalexperience. From his own role in shapinghealth care policy, he charts the trends andchanges in scientific research over the pastyears that accompanied the doubling of theNIH research budget. A statistic aboutfunding success (or lack thereof) for newinvestigators makes the entire M.D.-Ph.D.student group shudder collectively; as awhole, though, Dr. Nathan paints the pictureof a challenging but optimistic future for

scientific research. He describes the storyof one of his own long-time patients, andhow this patient’s therapy has evolved withprogressing scientific and pharmacologicknowledge.

The afternoon is full of Octobercold and rain, but that doesn’t keep peoplefrom playing golf, going hiking in the WhiteMountains, and exploring Waterville Valleyduring the free time. In the evening,everyone reconvenes for the traditionallobster bake and a festive mix of dancing-talking-pool playing-World Series watching-socializing. Somewhere between Shakira andEminem (informal verdict: genius) the firstand sixth year M.D.-Ph.D. classes lead theway on the dance floor, and the fanfare lastswell into the night.

The next morning, we’re drivinghome on I-93 back to Boston. We stop off atthe Hawaiian Isle II, a campy-lookingrestaurant on the outskirts of Concord. Atthe 1999 retreat, Rebecca and I had stoppedhere on the way home, and were charmedby the faux-Polynesian cocktails, typo-ridden Chinese Zodiac placemats and stalefortune cookies. The Hawaiian Isle IIstopover has been our retreat tradition eversince.

We’re sitting around the table, andRebecca mentions how the M.D.-Ph.D.retreat is that one time in the year when you

get to gather with everyone in the programand meet all the new students. Whilepreserving its founding ideals, the retreathas grown and evolved from its beginningstwenty years ago; I wonder, as I crack openthis year’s fortune cookie, what it will looklike twenty years from now.

Bryan K-H. Sun is a fifth year M.D.-Ph.D.

Program student (Holmes, DMS, BBS-Genetics).

5Harvard M.D.-Ph.D. Program Newsletter Fall/Winter 2002

Celebrity Chefs and Knockout Jockeysby Lilit Garibyan and Onyi I. Iweala

In his welcoming speech to the HMS/HSDMClass of 2006, Dean Daniel Lowensteinremarked that in their exit interviews,graduating medical students consistentlyreported that the most enjoyable part of theirmedical school experience was getting toknow their classmates. After only fourmonths in the M.D.-Ph.D. Program, we findthat the dean’s words ring true.

For example, this summer, throughthe required M.D.-Ph.D. course for first yearM.D.-Ph.D. candidates, we had theopportunity to get to know our classmatesfairly well. While we enjoyed our interactionsin the classroom, the most intriguing part ofour summer experience was coming to realizethe depth and diversity of our classmates’experiences prior to their arrival at HMS.Collectively, the 11 M.D.-Ph.D. studentsrepresent several different countriesincluding Armenia, India, Iran, Israel, Korea,Mexico, Nigeria, and the United States.What is more, as our short autobiographiesbelow reveal, we have strong academicresearch backgrounds and diverse researchinterests.

Even though we’ve entered ourrespective medical school curriculums (sevenof us are in the Health Sciences andTechnology (HST) while four of us arefollowing the New Pathway), we stillmaintain close ties with each other. Forinstance, under the direction of KushParmar, we have started the “Kush Parmar’sCelebrity Chef Series.” This dinner cluballows us to get together every Tuesdayevening to enjoy meals prepared by one ofour own classmates.

We recognize the importance ofestablishing firm bonds with our M.D.-Ph.D.classmates. After all, two years from now,we’re going to have to help each other makethe transition from medical school tograduate school. Furthermore, therelationships we build now will serve us wellin the future.

This is how our classmatesdescribe themselves:

Divya Bolar graduated in 2000 fromJohns Hopkins University with degrees inBiomedical Engineering and ElectricalEngineering. For the last two years, Div has

been engaged in cardiac and pulmonaryfunctional MRI research at the Universityof California, San Diego. At HMS, Div plansto focus on neuroimaging for his graduatestudies. He is specifically interested inusing novel MRI imaging paradigms toexplore task-based brain activity. Outsideof school, Div’s interests includeinternational travel, surfing, teaching,playing guitar, and attending live concerts.

Sarah Henrickson, a 2001graduate of Harvard College, joined theM.D.-Ph.D. Program hoping to combinebasic research and clinical medicine. Pastresearch included topics fromenvironmental science to biophysics andimmunology, which basically means shehasn’t quite settled on a field yet, but isenjoying trying different things. She spentthe last year at NIH, studying cancer usingDNA microarrays and planning herwedding. She hopes to find a project thatcombines exciting techniques and basicscience with clinical and biotechnologicalapplications.

Kush Parmar graduated fromPrinceton in 2002 with a degree in molecularbiology. His parents are from India, but hewas born in New Jersey. When he was oneyear old, his family moved to Veracruz,Mexico and they have lived there ever since.His interests include art history, anythingmedieval, flamenco guitar, and internationaldevelopment. One of his biggestcommitments is running a non-profitorganization (the Cruz Blanca Initiative)that undertakes sustainable developmentprojects in rural areas of Veracruz. He’sthrilled to be here and meet all the amazingpersonalities that make up the M.D.-Ph.D.community, and he looks forward to a funexperience.

Marlys Fassett, a native ofWisconsin, studied biochemistry as astudent at Harvard College. In herundergraduate research, she examined theinteraction between signaling andmembrane microdomains during immunecell recognition. Apart from school, Marlysenjoys performing chamber music, cookingfor friends, and reading literature. Shehopes to complement her HST M.D. with a

Ph.D. in either immunology ordevelopmental biology.

Onyi Iweala is a 2002 graduateof Harvard College, where she receivedan A.B. in Biochemical Sciences. Herundergraduate research centered on theeffect of parasitic infections on the immuneresponse to oral vaccines. She is quiteexcited about the New Pathwaycurriculum, but is worried that she may besuffering from thoracic outlet syndromefrom toting Moore’s Clinically Oriented

Anatomy around in her backpack one toomany times. Onyi hopes to contribute toefforts to improve access to preventivemedicine and primary care forunderprivileged populations. Her firsthand exposure to the challenges of drugand vaccine delivery in Cambodia andNigeria has spurred her interest in researchcentered on developing drugs or vaccinesthat are inexpensive and easy to administerto people in the developing world.

The M.D.-Ph.D. Program

Newsletter

Volume 13, No. 2

Editor

Linda BurnleyAssociate Editor

Tara O’MalleyAssistant Editor

Robin Lichtenstein

This newsletter is published twice a year.

Comments and ideas are welcome.

* * * * * * * * *

Nancy C. Andrews, M.D., Ph.D.Director

David E. Golan, M.D., Ph.D.Co-Director

Linda BurnleyDirector of Administration & Finance

Yi ShenSenior Financial Analyst

Robin LichtensteinAdmissions Specialist

Tara O’MalleyCommunications Specialist

Jennifer Au-YeungStaff Assistant

continued on page 6

6 Harvard M.D.-Ph.D. Program Newsletter Fall/Winter 2002

For the Record

Ph.D.s CompletedSandeep Robert Datta, Castle, BBS-

Microbiology and Molecular Genetics

(DMS) at Harvard University [MichaelGreenberg, Ph.D.] Coupling Growth Factorsto the Apoptotic Machinery: Biochemicaland Genetic Elucidation of the PI-3-Kinase/Akt/BAD Survival Signaling Cascade (8/02).

Anna Greka, Health Sciences andTechnology, Neuroscience (DMS) atHarvard University [David Clapham, M.D.,Ph.D.] TRP Channels and the Cytoskeleton:Implications for Neuronal Growth andCellular Motility (10/02).

Chao-Wei Hwang, Health Sciences andTechnology, Engineering Sciences, Medical

Engineering & Medical Physics atMassachusetts Institute of Technology [ElazerEdelman, M.D., Ph.D.] Local Pharmacokineticsof Stent-Based Drug Delivery (5/02).

Rahul Manu Kohli, Health Sciences andTechnology, BBS-Biological Chemistry and

Molecular Pharmacology (DMS) at HarvardUniversity [Christopher T. Walsh, Ph.D.]Macrocyclization Catalysis by ExcisedThioesterase Domains from Natural ProductSynthetases (11/02).

Gisela Maria Rodriguez Sandoval,Health Sciences and Technology,Neuroscience (DMS) at HarvardUniversity [Gary Ruvkun, Ph.D.]Molecular Genetic Analysis of anInteraction between the VesicularAcetylcholine Transporter andSynaptobrevin in Caenorhabditis

Elegans (7/02).

Lilit Garibyan graduated fromUCLA in 2001 with a degree in Microbiologyand Molecular Genetics. She was born inArmenia but at age twelve she moved toCalifornia with her family and has been livingthere ever since. At UCLA her research mainlyfocused on bacterial genetics. Lilit loves toteach, play basketball and talk about Armenianpeople. Her favorite virus is KSHV, herfavorite molecule is DNA and her favorite bookis “The Double Helix” by James D. Watson.In the future she hopes to work at a universitywhere she can teach, attend to patients andmaintain her own research laboratory.

Jubin Ryu graduated from Stanfordin 2001 with degrees in English and BiologicalSciences. He is interested in definingmechanisms behind cognitive processes suchas learning and memory using molecular,biochemical, and electrophysiological tools. Inthe future, he hopes to integrate basic scienceresearch with clinical and teaching duties.

Scott Vafai graduated in 2002 fromPrinceton University with a degree inmolecular biology. As an undergraduate, heconducted research on the molecular basis ofAlzheimer’s Disease. Scott is currently in theHST program and plans to do his Ph.D. in theneuroscience program.

Marc Wein joins the M.D.-Ph.D.Program in the New Pathway after graduatingfrom Yale University in 2002 with a BS/MSdegree in Molecular, Cellular, andDevelopmental Biology. Marc’s research

background is in signal transduction, in thecontext of behavioral neuroscience andinflammatory responses. In his graduate work,Marc intends to apply knowledge of basicmechanisms of signaling to the study oflymphocyte development and differentiation,hoping to gain insight into the cell biologyunderlying disorders such as autoimmunediseases and hematopoietic neoplasias. Marc’sfavorite anatomical structures are the thoracicduct and the left recurrent laryngeal nerve.

Sonia Cohen graduated from JohnsHopkins with an undergraduate degree insystems neuroscience before joining HST thisfall. In her previous research at Hopkins shestudied the role of the transcription factor CREBin mediating sympathetic nervous systemsurvival and growth. Sonia is interested incontinuing to study signal transduction –especially regulatory mechanisms that influencedifferential transcription, but is also exploringother areas of research.

Ruth Foreman is coming fromPhiladelphia, Pennsylvania where she studiedbiochemistry and the history and sociology ofscience at the University of Pennsylvania. Whilethere she was involved in musical theater. Forthe past year she worked in developmentalbiology at Penn’s Medical School studying therole of a gene (Foxd3) in early mouseembryogenesis. She was also known tomoonlight as a yoga and Pilates teacher (andstudent).

Student Receives Award

Congratulations to M.D.-Ph.D.Program student Michelle Lee

who was recently selected as theWilliam and Charlotte CadburyScholar by the National MedicalFellowships, Inc. This award is“presented annually to a senior,underrepresented medical studentin recognition of outstandingacademic achievement, leadership,and community service.” Shetraveled to the AAMC Conferencein San Francisco to receive theaward.

Staff Update

Welcome Jennifer Au-Yeung

who joined the office in Septemberas the new staff assistant. Jengraduated from Boston Universityin 2002 with a B.A. degree inEconomics.

Alumni Readers

Update your contact informationby emailing any changes tomdphd@hms.harvard.edu. Storyideas for the newsletter are alsoalways welcome.

Celebrity, from page 5

BBS = Biological and

Biomedical Sciences

DMS = Division of Medical

Sciences, Harvard Graduate

School of Arts and Sciences

Program Briefings

7

For the Record

Harvard M.D.-Ph.D. Program Newsletter Fall/Winter 2002

Recent PublicationsKim DH, Sarbassov DD, Ali SM, King JE, Latek RR, Erdjument-Bromage H, TempstP, Sabatini DM. mTOR interacts with raptor to form a nutrient-sensitive complex thatsignals to the cell growth machinery. Cell. 2002 Jul 26;110(2):163-75.

Dubinsky B, Vaidya AH, Rosenthal DI, Hochman C, Crooke JJ, DeLuca S, DeVine A,Cheo-Isaacs CT, Carter AR, Jordan AD, Reitz AB, Shank RP. 5-Ethoxymethyl-7-fluoro-3-oxo-1,2,3,5-tetrahydrobenzo[4,5]imidazo[1,2a]pyridine-4-N- (2-fluorophenyl)carboxamide (RWJ-51204), a New Nonbenzodiazepine Anxiolytic.J Pharmacol Exp Ther. 2002 Nov;303(2):777-90.

Fricker-Gates RA, Shin JJ, Tai CC, Catapano LA, Macklis JD. Late-stage immatureneocortical neurons reconstruct interhemispheric connections and form synaptic contactswith increased efficiency in adult mouse cortex undergoing targeted neurodegeneration.J Neurosci. 2002 May 15;22(10):4045-56.

Chang TT, Kuchroo VK, Sharpe AH. Role of the B7-CD28/CTLA-4 pathway inautoimmune disease. Curr Dir Autoimmun. 2002;5:113-30.

Akbari O, Freeman GJ, Meyer EH, Greenfield EA, Chang TT, Sharpe AH, Berry G,DeKruyff RH, Umetsu DT. Antigen-specific regulatory T cells develop via the ICOS-ICOS-ligand pathway and inhibit allergen-induced airway hyperreactivity. Nat Med.2002 Sep;8(9):1024-32.

Jabs C, Greve B, Chang TT, Sobel RA, Sharpe AH, Kuchroo VK. Genetic backgrounddetermines the requirement for B7 costimulation in induction of autoimmunity. Eur J

Immunol. 2002 Sep;32(9):2687-97.

Chen CC, Hsu L, Hecht JL, Janecka I. Bimaxillary chondrosarcoma: clinical, radiologic,and histologic correlation. AJNR Am J Neuroradiol. 2002 Apr;23(4):667-70.

Beltran-Valero De Bernabe D, Currier S, Steinbrecher A, Celli J, Van Beusekom E, VanDer Zwaag B, Kayserili H, Merlini L, Chitayat D, Dobyns WB, Cormand B, LehesjokiAE, Cruces J, Voit T, Walsh CA, Van Bokhoven H, Brunner HG. Mutations in the O-Mannosyltransferase Gene POMT1 Give Rise to the Severe Neuronal Migration DisorderWalker-Warburg Syndrome. Am J Hum Genet. 2002 Nov;71(5):1033-43.

Corbo JC, Deuel TA, Long JM, LaPorte P, Tsai E, Wynshaw-Boris A, Walsh CA.Doublecortin is required in mice for lamination of the hippocampus but not the neocortex.J Neurosci. 2002 Sep 1;22(17):7548-57.

Orange JS, Fassett MS, Koopman LA, Boyson JE, Strominger JL. Viral evasion ofnatural killer cells. Nat Immunol. 2002 Nov;3(11):1006-12.

Hanna LA, Foreman RK, Tarasenko IA, Kessler DS, Labosky PA. Requirement forFoxd3 in maintaining pluripotent cells of the early mouse embryo. Genes Dev. 2002 Oct15;16(20):2650-61.

Zhang X, Friedman A, Heaney S, Purcell P, Maas RL. Meis homeoproteins directlyregulate Pax6 during vertebrate lens morphogenesis. Genes Dev. 2002 Aug 15;16(16):2097-107.

Humpherys D, Eggan K, Akutsu H, Friedman A, Hochedlinger K, Yanagimachi R,Lander ES, Golub TR, Jaenisch R. Abnormal gene expression in cloned mice derivedfrom embryonic stem cell and cumulus cell nuclei. Proc Natl Acad Sci U S A. 2002 Oct1;99(20):12889-94.

Miller JH, Funchain P, Clendenin W, Huang T, Nguyen A, Wolff E, Yeung A, ChiangJH, Garibyan L, Slupska MM, Yang H. Escherichia coli Strains (ndk) Lacking NucleosideDiphosphate Kinase Are Powerful Mutators for Base Substitutions and Frameshifts inMismatch-Repair-Deficient Strains. Genetics. 2002 Sep;162(1):5-13.

Halfon MS*, Grad Y*, Church GM, Michelson AM. Computation-based discovery ofrelated transcriptional regulatory modules and motifs using an experimentally validatedcombinatorial model. Genome Res. 2002 Jul;12(7):1019-28.

Hanna J, Carroll K, Pfeffer SR. Identification of residues in TIP47 essential for Rab9binding. Proc Natl Acad Sci U S A. 2002 May 28;99(11):7450-4.

Leggett DS, Hanna J, Borodovsky A, Crosas B, Schmidt M, Baker RT, Walz T,Ploegh H, Finley D. Multiple associated proteins regulate proteasome structure andfunction. Mol Cell. 2002 Sep;10(3):495-507.

Esler WP, Das C, Campbell WA, Kimberly WT, Kornilova AY, Diehl TS, Ye W,Ostaszewski BL, Xia W, Selkoe DJ, Wolfe MS. Amyloid-lowering isocoumarins are notdirect inhibitors of gamma-secretase. Nat Cell Biol. 2002 May;4(5):E110-1; discussionE111-2.

Kimberly WT, LaVoie MJ, Ostaszewski BL, Ye W, Wolfe MS, Selkoe DJ. Complex N-linked Glycosylated Nicastrin Associates with Active gamma -Secretase and UndergoesTight Cellular Regulation. J Biol Chem. 2002 Sep 20;277(38):35113-7.

Kohli RM, Walsh CT, Burkart MD. Biomimetic synthesis and optimization of cyclicpeptide antibiotics. Nature. 2002 Aug 8;418(6898):658-61.

Lorenzo ME, Jung JU, Ploegh HL. Kaposi’s sarcoma-associated herpesvirus K3 utilizesthe ubiquitin-proteasome system in routing class major histocompatibility complexes tolate endocytic compartments. J Virol. 2002 Jun;76(11):5522-31.

McDonald WH, Ohi R, Miyamoto DT, Mitchison TJ, and Yates JR 3rd. Comparisonof three directly coupled HPLC MS/MS strategies for identification of proteins fromcomplex mixtures: single-dimensional LC-MS/MS, 2-phase MudPIT, and 3-phaseMudPIT. International Journal of Mass Spectrometry. 2002; 219, 245-251.

Murnick JG, Dube G, Krupa B, Liu G. High-resolution iontophoresis for single-synapsestimulation. J Neurosci Methods. 2002 Apr 30;116(1):65-75.

Goodwin TE, Brown FD, Counts RW, Dowdy NC, Fraley PL, Hughes RA, Liu DZ,Mashburn CD, Rankin JD, Roberson RS, Wooley KD, Rasmussen EL, Riddle SW,Riddle HS, Schulz S. African elephant sesquiterpenes. II. Identification and synthesis ofnew derivatives of 2,3-dihydrofarnesol. J Nat Prod. 2002 Sep;65(9):1319-22.

Eden S, Rohatgi R, Podtelejnikov AV, Mann M, Kirschner MW. Mechanism of regulationof WAVE1-induced actin nucleation by Rac1 and Nck. Nature. 2002 Aug15;418(6899):790-3.

Loureiro JJ, Rubinson DA, Bear JE, Baltus GA, Kwiatkowski AV, Gertler FB. CriticalRoles of Phosphorylation and Actin Binding Motifs, but Not the Central Proline-richRegion, for Ena/Vasodilator-stimulated Phosphoprotein (VASP) Function during CellMigration. Mol Biol Cell. 2002 Jul;13(7):2533-46.

Kornhauser JM, Cowan CW, Shaywitz AJ, Dolmetsch RE, Griffith EC, Hu LS, HaddadC, Xia Z, Greenberg ME. CREB transcriptional activity in neurons is regulated bymultiple, calcium-specific phosphorylation events. Neuron. 2002 Apr 11;34(2):221-33.

Shendure J, Church GM. Computational discovery of sense-antisense transcription inthe human and mouse genomes. Genome Biol. 2002 Aug 22;3(9):RESEARCH0044.

Stover EH, Borthwick KJ, Bavalia C, Eady N, Fritz DM, Rungroj N, Giersch AB,Morton CC, Axon PR, Akil I, Al-Sabban EA, Baguley DM, Bianca S, Bakkaloglu A,Bircan Z, Chauveau D, Clermont MJ, Guala A, Hulton SA, Kroes H, Li Volti G, Mir S,Mocan H, Nayir A, Ozen S, Rodriguez Soriano J, Sanjad SA, Tasic V, Taylor CM,Topaloglu R, Smith AN, Karet FE. Novel ATP6V1B1 and ATP6V0A4 mutations inautosomal recessive distal renal tubular acidosis with new evidence for hearing loss.J Med Genet. 2002 Nov;39(11):796-803.

*Equal contributors.

8 Harvard M.D.-Ph.D. Program Newsletter Fall/Winter 2002

For the Record

M.D.-Ph.D. Program

Harvard Medical School

Tosteson Medical Education Center260 Longwood Avenue, Room 168Boston, Massachusetts 02115-5720

mdphd@hms.harvard.eduhttp://www.hms.harvard.edu/md_phd

(617) 432-0991 (phone)(617) 432-2791 (fax)

Incoming M.D.-Ph.D. Students, 2002-2003

Top L-R: Marc Wein, Divya Bolar, Sarah Henrickson, Kush Parmar andLilit Garibyan. Bottom L-R: Marlys Fassett, Sonia Cohen, Ruth Foreman,Onyinye Iweala, Jubin Ryu and Scott Vafai.

Divya S. Bolar of Martinsville, NJ graduated from Johns HopkinsUniversity in 2000 with a BS in Biomedical Engineering, ElectricalEngineering.

Sonia Cohen of Kenilworth, IL earned a BA in Neuroscience from JohnsHopkins University in 2002.

Marlys S. Stempihar Fassett of Beloit, WI graduated from HarvardCollege in 2001 with an AB in Biochemical Sciences.

Ruth K. Foreman of Harrisville, PA completed a BA in Biochemistry,History and Sociology of Science from the University of Pennsylvania in2001.

Lilit Garibyan of Glendale, CA graduated from UCLA in 2001 with a BSin Microbiology and Molecular Genetics.

Sarah E. Henrickson of Takoma Park, MD received an AB in BiochemicalSciences from Harvard College in 2001.

Onyinye I. Iweala of Potomac, MD graduated from Harvard College in2002 with an AB in Biochemical Sciences.

Kush M. Parmar of Boca del Rio, Veracruz graduated from PrincetonUniversity in 2002 with an AB in Molecular Biology.

Jubin W. Ryu of Morgantown, WV earned a BA/BS in English/BiologicalSciences from Stanford University in 2001.

Scott B. Vafai of Edison, NJ received an AB in Molecular Biology fromPrinceton University in 2002.

Marc N. Wein of Cheshire, CT graduated from Yale University in 2002with a BS, MS in Molecular, Cellular and Developmental Biology.

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