The Magazine of

The University of Massachusetts Medical School

fall/winter 2004, vol. 27 no. 1

Diabetes Pre-emption

Raising the Bar on Toll

A Place of Their Own

Vit e: L., the plural of life

The name of this magazine encompasses the lives of those who make up the UMMS community,

for which it is published. They are students, faculty, staff, alumni, volunteers, benefactors and

others who aspire to help this campus achieve national distinction in education, research and

public service.

University of Massachusetts Medical School

The University of Massachusetts Medical School was created in 1962 by an act of the

Massachusetts Legislature and today is comprised of three schools. Since accepting its first

class in 1970, the School of Medicine has provided students with an accessible, comprehensive

and personally rewarding medical education of the highest quality, one which optimally

prepares them to excel as physicians. The Graduate School of Biomedical Sciences, opened

in 1979, is a faculty-initiated PhD program that trains scientists in a specialty area with a broad

background in the basic medical sciences, in preparation for conducting research with direct

relevance to human disease. Opened in 1986, the Graduate School of Nursing, through its

master’s, post-master’s and doctoral degree programs, provides professional education and

training for advanced practice nurses within three specialties: adult acute/critical care nurse

practitioners, adult ambulatory/community care nurse practitioners and advanced practice

nurse educators.

Commonwealth Medicine

Commonwealth Medicine is UMass Medical School’s innovative public service initiative, provid-

ing expertise to public sector agencies so they may optimize their efficiency and effectiveness.

By offering access to its unparalleled breadth of academic, research, management and clinical

resources, Commonwealth Medicine assists agencies to enhance the value and quality of expen-

ditures, and improve access and delivery of care to at-risk and uninsured populations.

UMass Memorial Foundation

The UMass Memorial Foundation, established in May 1998, is the charitable partnership created

through a merger of the former University of Massachusetts Medical Center Foundation and the

Memorial Foundation. The mission of the Foundation is to support the academic and research

enterprises of UMass Medical School and the clinical initiatives of UMass Memorial Health Care.

Worcester Foundation for Biomedical Research

The Worcester Foundation for Biomedical Research is a nonprofit organization devoted to the

support of research and the education and training of tomorrow’s scientists at the University of

Massachusetts Medical School. Founded in 1944 as an independent basic biomedical research

institute, with research accomplishments that include the birth control pill and the work that led

to in vitro fertilization, the Worcester Foundation merged with UMass Medical School in 1997.

UMass Memorial Health Care

UMass Memorial Health Care is Central Massachusetts’ largest nonprofit health care delivery

system, covering the complete health care continuum with teaching hospitals, affiliated commu-

nity hospitals, free-standing primary care practices, ambulatory outpatient clinics, long-term

care facilities, home health agencies, hospice programs, a rehabilitation group and mental

health services. UMass Memorial is the clinical partner of the University of Massachusetts

Medical School.

News and Notes 2

Features 7

Grants and Research 21

Alumni Report 23

The Last Word 28

Contents

Diabetes Pre-emption 7A new UMMS clinical trial introduces weight control, nutrition and exercise initiatives to a population at high risk for developing diabetes, with implications for all.

Raising the Bar on Toll 12The discovery of immune response ‘Toll-like receptors’—and the leadership of UMMS researchers in exploring their significance—is revealing potential impact on a range of diseases.

A Place of Their Own 17UMMS and UMass Memorial gain designated space for conducting clinical research trials, key to expansion and potential designation as a General Clinical Research Center.

Research Team to Test New Protocol

for Islet Cell Transplantation

2

Michael P. Czech, PhD, UMMS professor and chair of molecularmedicine, was awarded the American Diabetes Association’s2004 Albert Renold Award in June. The award, named for therenowned physician and researcher, is given annually to an indi-vidual whose career is distinguished by outstanding achieve-ments in the training of diabetes research scientists or the facili-tation of diabetes research.

“I am honored to receive the Albert Renold Award in recognitionof my role in mentoring the many students and postdoctoral fel-lows who have passed through my lab,” Dr. Czech said. “I knowthat each and every one of them has made a contribution to fur-ther advancing our knowledge of diabetes and obesity.”

Throughout his career, Czech has studied type 2 diabetes, whichcurrently afflicts over 18 million Americans and is on the rise;his lab has made essential strides in understanding the funda-mental mechanisms of the disease. An integral member and asso-ciate director of the UMMS Diabetes Endocrinology ResearchCenter, one of 15 across the country funded by the NationalInstitutes of Health, Czech directs a lab group of 20 scientistswho are at the leading edge of research on diabetes, insulin

action and signal transduction pathways involved in metabolicdiseases. In 2000, Czech received the prestigious Banting Medalfrom the ADA.

UMMS Scientist Receives ADA Renold Award

Taking new steps in research aimed at abetter treatment for the most severe formof diabetes, two new clinical trials atUMass Medical School and UMassMemorial will soon transplant insulin-producing islet cells into a limited num-ber of patients with type 1 diabetes. Thesetransplant trials will use a novel protocolfor therapy that may help the patients livefree of insulin dependence—and in thelatest advance, one of the trials will useinsulin-producing cells isolated and cul-tured at UMMS.

“Our ultimate goal is to be able to trans-plant islet cells without the need for thepatients to stay on powerful immunosup-pressive drugs for the rest of their lives,”

said Aldo A. Rossini, MD, the Williamand Doris Krupp Professor of Medicineand chief of the Division of Diabetes atUMMS, leader of one of the teams prepar-ing for the islet transplantation. “We hopethis next round of trials will take us onestep closer to that goal.”

The new protocol, funded by the National Institutes of Health, is based, in part, upon the experience leaders in thefield gained while participating in theinternational Edmonton Protocol in 2002.At that time, UMMS was among 18 centers worldwide to participate in theclinical trial which tested a transplantprotocol first developed at the Universityof Alberta in Edmonton, Canada to reverse

the insulin dependence of diabeticsthrough islet cell transplantation.

As this issue of Vitae went to press,Cristiana Rastellini, MD, associate profes-sor of surgery, and an expert in the field of islet cell isolation, received approvalfrom the U.S. Food and DrugAdministration to isolate and culture isletcells for use in a transplantation clinicaltrial, making UMMS one of just 10 suchcenters in the country with permission to culture these insulin-producing cells.

Michael Czech, PHD, mentors Graduate School of Biomedical Sciencesstudent Nana Hagan.

Islet cells (left) and insulin molecules within them

News and Notes

Jean Sullivan, JD, special assistant to theDeputy Chancellor for CommonwealthMedicine at UMass Medical School, is thelatest UMMS employee to win the ManuelCarballo Governor’s Award for Excellencein Public Service. The Carballo Award ispresented annually to 10 state workerswho exemplify “the highest standards ofpublic service through exceptional accom-plishment, exemplary leadership, creativi-ty and productivity.” UMMS employeeshave received this honor in four of thepast six years.

Sullivan shares her extensive knowledgeof Medicaid law and federal reimburse-ment through her responsibilities atCommonwealth Medicine, where sheserves as the key liaison with the stateExecutive Office of Health and Human

Services. She was pivotal in the passage of the 2002 Act for a Healthy Common-wealth, implemented to stabilize thehealth care safety net by increasing support for Medicaid and for theUncompensated Care Pool, which paysfor medically necessary services provid-ed by acute care hospitals and communi-ty health centers to low-income unin-sured and underinsured individuals.

Sullivan also played a critical role in thedevelopment of the legislation that creat-ed the Division of Medical Assistance(DMA) and, most notably, was a leader indeveloping the Medicaid waivers thatcreated MassHealth, the state healthinsurance program responsible for direct-ly reducing the number of uninsured residents in the state.

Commonwealth Medicine Executive Wins Carballo

Arthur M. Mercurio, PhD, whose career hasfocused on the mechanisms of invasive andmetastatic cancer, has been appointed vicechair of the Department of Cancer Biology.Formerly the director of the Division ofCancer Biology and Angiogenesis in theDepartment of Pathology at Beth IsraelDeaconess Medical Center and HarvardMedical School, Dr. Mercurio joined UMMSas a professor of cancer biology this fall.

“Art Mercurio is a leader in the field ofbreast cancer research and brings to ourcancer program more than 20 years of expe-rience in tumor cell biology,” said Dario C.Altieri, MD, the Eleanor Eustis FarringtonChair in Cancer Research and chair of theDepartment of Cancer Biology. “He has along history of translational oncologyresearch and a vision to further build ourresearch program and its interface with ourclinical efforts.”

Mercurio, whose research is focused onunderstanding the biology that contributesto the metastasis, or spread of solid tumors,particularly breast and colon cancers, willwork closely with Azra Raza, MD, chief ofthe Division of Hematology-Oncology in theDepartment of Medicine, to spearhead theclinical cancer research initiatives at UMassMemorial Medical Center. Mercurio willalso become the program leader of the solidtumor initiative at UMMS.

“My goal is to use the outstanding basic science here as a foundation for buildingprograms that unravel mechanisms ofmetastasis and to work with oncologistsand pathologists to translate this knowl-edge into more effective approaches forthe clinical management of solid tumors,”said Mercurio.

Jean Sullivan, JD

Renowned Cell Biologist Joins Cancer Biology

Arthur Mercurio, PhD

3

Accreditation Visit Reveals

GSN Achievements

4

The Graduate School of Nursing completed a successful accredita-tion visit in early October by the Collegiate Commission on NursingEducation, an official accrediting body for U.S. baccalaureate andhigher degree nursing programs. This on-site review followed sever-al weeks and months of a self-study process undertaken by the GSNto evaluate the effectiveness of the graduate nursing education pro-grams, assess the program’s broad educational goals and examinethe teaching environment of the graduate nursing students.

The CCNE validated that the GSN has met and is in compliancewith each of the four areas: Mission and Governance, InstitutionalCommitment and Resources, Curriculum and Teaching LearningPractices, and Student Performance and Faculty Accomplishments. Students interact during a Graduate Entry Pathway class, one

of the GSN’s innovative programs.

MERIT Award Recognizes UMMS Professor’s

Sustained Excellence

News and Notes

UMMS Chancellor and Dean Aaron Lazarereceived critical acclaim for his book OnApology, published by Oxford UniversityPress in late August. The book exploresthe components of an effective and

sincere apology and how apology can be a healing act of honesty, humility and generosity in both interpersonal and international relations. Calling it a “jewelof a book that reveals the many facets of

the seemingly simple act of apology,”Publisher's Weekly gave On Apology astarred review in its Sept. 27 issue.“Drawing on a vast array of literary andreal-life examples...Lazare succeeds in

Professor of Pathology Raymond Welsh, PhD, first received thegrant, “Immunity and Virus Disease,” in 1975 while at theScripps Clinic in California. He brought the grant with him whenhe joined UMMS in 1980 and, in a recent letter to the NationalInstitutes of Health (NIH), described a number of discoveriesabout basic mechanisms of viral immunology andimmunopathology gleaned over the past 29 years from the grant’s studies of viral infections in mouse models.

For this sustained record of scientific productivity, the NIH hasawarded Welsh a highly selective extension on the grant for 10years–in the form of back-to-back, five-year grants–totalingapproximately $4 million. The Method to Extend Research inTime, or MERIT Award, recognizes investigators whose research

competence and productivity are distinctly superior, and who are likely to continue to perform in an outstanding manner.

The MERIT Award also acknowledged Welsh’s contributions inteaching; he has trained the most UMMS PhD graduate students,11, of any GSBS faculty member to date and credits the graduatestudents, post-doctoral fellows and junior faculty who haveworked in his lab with assisting in the development of the datathat helped secure the MERIT Award.

Other UMMS investigators who have received NIH MERITAwards include Mario Stevenson, PhD, the David J. FreelanderProfessor of AIDS Research, and Steven N. Treistman, PhD, professor of neurobiology and anesthesiology.

On Apology a Critical Success

Radiation Oncology Department Established

showing that a true apology is among the mostgraceful and profound of all humanexchanges,” the review read. “When it is sin-cere, [an apology] is not an end but a newbeginning....Everybody on earth could benefitfrom this small but essential book.”

In addition to Publisher’s Weekly, On Apologyhas been reviewed or featured by Oprahmagazine, The Forward, the San FranciscoChronicle, Real Simple magazine, ESPN’s“Outside the Lines” and Boston’s ABC affiliateWCVB-TV.

‘Blue Ribbon’ Honors Lamar Soutter Library

The growth of the UMass Medical Schooland UMass Memorial cancer research and care programs, and the increasedinteraction between radiation oncologistsand their colleagues in departments suchas Cancer Biology, led to the recent establishment of the Division of RadiationOncology as a department.

“The members of the division are widelyregarded for their expertise,” notedChancellor and Dean Aaron Lazare.

“While their primary appointments in anumber of different departments and divi-sions speak to the multidisciplinarynature of the specialty, having a commonacademic department makes good sense,and enhances our ability to recruit andretain academic physicians in this special-ty.” The administrative change is expectedto promote future research, academic andclinical care achievements in a vital area of cancer research and treatment.

Thomas (T. J.) FitzGerald, MD, leads thedepartment as its chair. A 1980 graduate of UMMS and incumbent chief of theDivision of Radiation Oncology, Dr. FitzGerald is a noted academic radiation therapist who is widely published and serves as director of theQuality Assurance Review Center, a National Cancer Institute-funded programfor several important treatment protocols.

The Lamar Soutter Library has received a 2004 Blue Ribbon Consumer HealthInformation Recognition Award forLibraries from the National Commissionon Libraries and Information Science

(NCLIS). The award recognizes one libraryin each state that best promotes a healthylifestyle for its citizens; the libraries arenominated by state library agencies andwinners are chosen based on the overall success of the library’s consumer healthinformation services program, withemphasis on the program’s potentialimpact, innovativeness and adaptability.

The Soutter Library was one of threeMassachusetts libraries nominated. It wasparticularly recognized for its role in pro-viding information to the families ofchronically ill children through the estab-lishment of a pediatric library and for itstraining and outreach services providedthrough the Regional Medical Library

grant program. In the award letter, sent toDirector of Library Services Elaine R.Martin, MSLS, the commission’s ChairBeth Fitzsimmons, PhD, wrote, “TheLamar Soutter Library’s...innovative creation and distribution of consumerhealth information has enabledMassachusetts to strengthen and build itsconsumer health information services,resulting in a healthier, well-informedcommunity of users. The Library...epito-mizes the concept of knowledge develop-ment and knowledge sharing, one of thebasic tenets of professional librarianship.”

Aaron Lazare, MD, at a recentbook signing

5

6

Blue Cross Blue Shield of Massachusettsreturned this year as the presenting spon-sor for the sixth annual Walk to CureCancer, held Sunday, September 26. Thecompany also pledged $50,000 per yearfor the next three years, beginning withthe 2004 Walk.

Blue Cross Blue Shield participated in theinaugural Walk in 1999 and again in 2000as a water stop and team sponsor. “In 2001,we were particularly inspired by theMassachusetts AFL-CIO’s impressive participation in the Walk to Cure Cancerand compelled to match that commitmentwith our own contribution,” said SeniorVice President of Corporate Relations FrediShonkoff. “We applaud the collaborationbetween the Mass. AFL-CIO and UMassMedical School with its clinical partner,UMass Memorial Health Care, in the effortto battle cancer, and are thrilled to continueour partnership with the Walk.”

Over the years, Blue Cross Blue Shieldemployees who make up the “Blue Crew”have become integral to the success of the Walk, volunteering at water stops and along the route, as well as raisingfunds as they walk for a cure. Many of the 700 employees on the team have feltthe impact of cancer—one is a nine-yearsurvivor of brain cancer, for example. Forthis and many other similar reasons,members of the Blue Crew will continueto be a strong presence.

Blue Cross Blue Shield of Massachusetts,in partnership with the Mass. AFL-CIO,was joined by other corporate and mediasponsors of the Walk, including Verizon,FleetBoston, NSTAR, Raytheon, PolarCorporation, Stop & Shop, New EnglandCable News, Worcester Telegram & Gazetteand WSRS-FM/WTAG-AM. Flagship spon-sors were: UMass Memorial Health Care,CWA Local 1301, Mailhandlers of N.E.

Local 301, UFCW Local 1445, College ofthe Holy Cross and Worcester FitchburgBuilding Trades Council.

News and Notes

Corporate and Community Sponsorship Ensures Successful

Walk to Cure Cancer

Members of presenting sponsor Blue Cross BlueShield of Massachusetts’ “Blue Crew” joined some8,000 other participants at the 2004 Walk, whichraised approximately $660,000 for UMMS cancerresearch programs. Top, from left: Tom Cabral, Elaine Ermanski, Eileen Marsh, Teri Doucette andDave Rudick; bottom, from left: Diana Poole, KarieLee, Deb Mikelonis and Patricia Peters

6

Rod Miller, a highly regarded develop-ment professional, was named chief exec-utive of the UMass Memorial Foundationin June. He is leading the joint develop-ment and outreach functions of theschool and clinical system as UMMSVice Chancellor for Development andUMass Memorial Health Care VicePresident for Development.

“Rod’s accomplishments as a fundraiserare impressive, but his talent for engendering involvement andnurturing support in a way that builds long and mutually pro-ductive relationships strikes us as his real strength,” saidChancellor and Dean Aaron Lazare.

Miller joined the UMass Memorial Foundation from his mostrecent position as vice president for institutional advancement at the Cold Spring Harbor Laboratory in New York, one of theworld’s eminent biomedical research institutions. Previously, he developed comprehensive fund-raising and alumni programsat Polytechnic University in Brooklyn and QueenslandUniversity of Technology in his native Australia.

“With the fruits of the Human Genome Project in hand, the challenge to treat many debilitating diseases is no longer theoretical or technical, but financial,” said Miller. “I am delighted to be joining the effort to develop opportunity for philanthropic investment that furthers the biomedical discoveryand health care at UMass Medical School and UMass Memorial.”

Miller Named UMass Memorial Foundation Chief Executive

7

By Michael I. Cohen

Diabetes Pre-emptionAn ambitious UMMS initiative introduces weight control, nutrition and

exercise programs to a population at high risk for developing

diabetes, with implications for all.

Elliot Joslin, founder of the famed diabetes clinic thatbears his name, said nearly 100 years ago that with diabetes, genetics loads the cannon, but obesity pulls thetrigger. Today, among the Latino population of the UnitedStates, the cannons of diabetes are booming.

To address the soaring incidence of diabetes among Latinos,both in the Commonwealth and across the country, UMassMedical School and the Greater Lawrence Family HealthCenter (GLFHC) have embarked on an ambitious clinicaltrial to test a program that researchers hope will prevent theonset of type 2 diabetes among members of the Latino popu-lation in Lawrence, Massachusetts. And if the trial succeedsthere, it could point the way to a cost-effective approach forpreventing type 2 diabetes in all populations.

“If we show that we can prevent diabetes among Latinos inLawrence, then I would hope third-party payers would startcovering this kind of intervention for anyone who needs it,”said Ira S. Ockene, MD, principal investigator of the clinicaltrial and the David J. and Barbara D. Milliken Professor ofPreventive Cardiology and professor of medicine at UMMS.“Right now third-party payers are willing to pay $50,000 tohave stents placed in your heart when you are sick, butthey’re not willing to pay $1,000 for the counseling that

might prevent you from becoming sick. That’s unfortunate, and Ihope if our study is successful, that will change.”

Dr. Ockene’s reference to heart disease in the context of a diabetesprevention program is hardly casual. The consequences of dia-betes left unchecked are severe, including heart disease, stroke,blindness and kidney failure. “Diabetes is an extraordinary riskfactor for heart disease,” Ockene said. “The major cause of deathamong diabetics is heart disease. So as a cardiologist, I have everyreason to be interested in diabetes, just as I have every reason tobe interested in smoking, high blood pressure and cholesterol.”

Conversely, diabetes can be managed with great success. Wellunderstood measures, such as weight control, proper nutritionand increased physical activity can help most diabetics avoidthe severe complications of the disease. So Ockene and his col-leagues will attempt to translate that body of knowledge to helppeople who do not yet have diabetes remain free of the disease. “Based on all the studies we have done previously onhow you get people to change their nutrition and physical activ-ity, we believe we can develop an intervention that will be sim-ple and workable in the real world—even in a very challengingenvironment like the one in Lawrence,” said Ockene.

Nutritionists like Migna Alecon (left) will take participants in theclinical trial food shopping, to help them select items that fit theprotocol for diabetes prevention. She visits the El Pilon market inLawrence, owned by Cesar Arias (right).

8

“A confluence of factors here add up

to diabetes being much worse

for Latinos in Lawrence.”

– Trinidad Tellez, MD (above center, and on page 7),

who will oversee the clinical trial’s operations on a daily basis.

She’ll be helped by Alexandra Luciano (left) and Nelida Vatcher (right).

John P. Mordes, MD, professor of medicine,a diabetes researcher and clinician atUMMS, worked as a consultant withOckene to craft the clinical trial. “I seemany Latinos in my clinic, so I know first-hand the magnitude of this problem,”Dr. Mordes said. “The goal of interveningbefore diabetes is present is, by far, prefer-able to providing care for someone whoalready has the disease. So it was a privi-lege for me to be asked by Dr. Ockene to beinvolved in the design of this trial.”

The effort is called the Lawrence LatinoDiabetes Prevention Project (LLDPP), a four-year, $2.6 million randomized clinical trial funded by the NationalInstitute of Diabetes and Digestive andKidney Diseases at the National Institutesof Health (NIH). The study brings togetheran array of community groups includingthe Lawrence Council on Aging/SeniorCenter, which will be the host site formuch of the programming; the YWCA ofGreater Lawrence, which will help withrecruitment and advise on communityissues; UMass Lowell, which will analyzethe blood samples from participants in thestudy; and the clinical and researchresources of UMass Medical School and theGLFHC. “This is an excellent partnershipbetween the academic researchers and the

community,” said Trinidad Tellez, MD, aclinician-researcher at the GLFHC, and aninstructor in family medicine & communityhealth at UMMS.

Dr. Tellez is a co-principal investigator ofthe prevention study. She’s also a member of the Executive Advisory Committee for the Massachusetts Diabetes Prevention andControl Program, which is working on astatewide diabetes action plan. “The bur-den of diabetes in Lawrence is high andthere are a lot of challenges delivering thisintervention,” Tellez said. “We believe thatif we can prevent diabetes here, anybodyshould be able to do it anywhere.”

According to the American DiabetesAssociation (ADA), some 18 millionAmericans now have type 2 diabetes (oftencalled adult onset diabetes, though thespike in obesity among children is drivinga similar increase in diabetes among youngpeople). More troubling is the rate ofincrease in the prevalence of the disease.According to federal statistics, the numberof people diagnosed with type 2 diabetesjumped nearly 30 percent between 1997and 2002.

While type 2 diabetes affects all segmentsof the population, it hits certain groupsharder. Latinos, Asians, African Americansand Native Americans are genetically more

susceptible to diabetes, and that predis-position is enhanced by environmentalor behavioral factors such as poverty andobesity that can hasten onset of the dis-ease. The result: these minority groupssuffer from diabetes at two to three timesthe rate of the majority population in theUnited States. In Massachusetts, theprevalence of type 2 diabetes amongLatinos is 8.4 percent, compared to 4.7percent for the Caucasian population.

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As principal investigator of the Lawrencediabetes study, Ira Ockene, MD, hopes it willyield dramatic results that can translate intoa national model for diabetes prevention.

Increasing daily physical activity is a key component of the clinical trial. Below, Lawrence residents representing a range of ages work out at the Senior Center.

In Lawrence, one of the poorest communities in theCommonwealth, the problem is even worse, with the prevalencerate now pegged at 11.8 percent for Latinos of Puerto Rican andDominican origin. “There’s a confluence of factors here that addup to diabetes being much worse for Latinos in Lawrence,”Tellez said.

As it tracked the soaring incidence of type 2 diabetes inLawrence, the GLFHC began working several years ago to helppatients better manage their diabetes. Funded by a REACH 2010grant from the U.S. Centers for Disease Control and Prevention,the health center developed educational and clinical protocolsaimed at diabetic Latinos. Under the leadership of DeanCleghorn, EdD, UMMS associate professor of family medicine &community health and a director of one of the GLFHC clinics,the REACH program has built an infrastructure of diabetes education and care within the health center. A cornerstone of

that effort is the Diabetes Self-Management Education Programthat was recently awarded “Education Recognition” from theADA. “REACH is very important and very successful,” saidTellez, who also works on the REACH project. “We know ithelps people who have diabetes. Now we’re trying to expand ourscope and help the 42,000 Latinos in Lawrence who don’t havethe disease, but who are at risk for developing diabetes.”

The Lawrence study will enroll a total of 400 Latinos who fallinto this category. The participants will be split into two groupsof 200 each, with one group (the control group) being given theusual care for non-diabetics now practiced in the Lawrence area.The other group (the intervention group) will participate in a 23-month-long series of programs designed by the research team tohelp reduce the risk of developing diabetes—primarily throughweight loss and increased physical activity. Both groups will befollowed for a year after the intervention classes end.

10

The Lawrence Latino Diabetes Prevention Project is not just a series of classroom sessions filled with facts and figures. Participants will cook together and dine together for several months at the Lawrence Senior Center, learning recipes and eating habits that are both satisfying and healthful.

The preventive programs for the group will include cooking class-es, exercise classes, strategies for food shopping and eating out at restaurants. There will be educational sessions about dia-betes, the risk factors that lead to diabetes, and the consequencesof the disease if left unchecked. The program will also includeseveral psychosocial elements to help people deal with issuessuch as self-efficacy and depression that play a pivotal role in aperson’s ability to change behaviors. “Long-term adherence is thekey to the success of this program,” said Milagros C. Rosal, PhD,assistant professor of medicine at UMMS and co-principal inves-tigator of the study. “When you want people to change, you haveto make the changes easy and appealing, otherwise they won’tadhere to them long-term. So we will try to build skills in situa-tions that resemble their day-to-day activity.”

Dr. Rosal works in the UMMS Division of Preventive andBehavioral Medicine. In the Lawrence study, Rosal will lead theeffort to develop the programs that will convey the educationalinformation on diabetes prevention to the intervention group. Shewill also develop practical literacy- and culturally sensitivestrategies to facilitate attitudinal and behavioral change. “TheLawrence population presents multiple challenges, including lan-guage, culture and literacy level,” Rosal said. “We’ll need to usevery little printed material, and we’re planning to deliver theentire intervention in Spanish.”

In that effort, Rosal will draw on insights she’s gleaned from several years of work studying factors that facilitate or inhibit diabetes self-management among low-literate Latinos. That population typically suffers higher complication rates and higherdeath rates from diabetes as compared to Caucasians, Rosal said.

“Interestingly, we found that the problem was not access to healthcare; nearly everyone in the groups we studied had access tohealth care and was seeing their doctor several times a year. Sothe key issue, I believe, is that patients may not be receiving the information they need about diabetes in ways they could processand integrate into their daily lives.”

Rosal is now working closely with clinicians, nutritionists andcounselors from UMMS and the GLFHC to finalize the methodsand materials to be used in the Lawrence clinical trial. Plans callfor a variety of group sessions, individual sessions, and follow-upphone calls to participants’ homes. Recruitment for the study willbegin this fall, and the first intervention classes are scheduled forJanuary 2005.

Throughout the study, researchers will track participants’weight, body/mass index, blood pressure, cholesterol and bloodglucose levels. That data will be used in a well-established for-mula that can predict a person’s chance of developing diabeteswithin seven years, based on their metabolic profile. The test ofthe Lawrence study will be to see if the intervention group sig-nificantly reduces its risk of diabetes, compared to the controlgroup. “Years ago when we studied cholesterol and heartattacks, we had to track people and prove we reduced the inci-dence of heart attacks in the group. We don’t do that anymorebecause the linkage is a given—now we just focus on reducingcholesterol, knowing that will reduce heart attacks,” Ockenesaid. “The same is true with diabetes. We don’t have to followthe people in this study for 10 years to see what will happen.Our goal is to gain the knowledge that if we reduce these riskfactors, the incidence of diabetes will be reduced.”

“When you want people to change, you have to make the

changes easy and appealing.... We will try to build skills in

situations that resemble their day-to-day activity.”

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– Milagros Rosal, PhD (left), has studied behavioral patterns of Latinos with diabetes in

Springfield, Massachusetts and drew upon the experience to design program

materials and methods for the Lawrence clinical trial.

Raising the Bar on TollThe discovery of immune response ‘Toll-like receptors’—and the leadership

of UMMS researchers in exploring their significance—is revealing potential

impact on a range of diseases.

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By Kelly A. Bishop

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For years, scientific inquiry into immunity was dominated by the study of the adaptive immune system—how thebody fights infection with the complexproduction of antibodies that specificallytarget an invading pathogen. In recentyears, however, a series of new discoverieshas reinvigorated the study of the innateimmune system, one with much in common among plants, insects andmammals. With the recent discovery thatthe gene Toll from the fruit fly(Drosophila) plays a critical role ininsect immunity, and the identificationof mammalian Toll counterparts called“Toll-like receptors,” innate immunity isbecoming one of the hottest areas of cur-rent research. Leading the way, UMassMedical School is rapidly building acore group of investigators who are fur-ther elucidating how Toll-like receptors(TLRs) work as a means to gain insightinto the innate immune response.

The innate immune system–the onlyform of immunity in insects and the pre-cursor to the adaptive immune system inmammals–acts as the first line of defenseagainst a range of pathogens. Whereasadaptive immunity involves the body’sresponse to an invading microorganismwith the production of specific antibodiesand lymphocytes that precisely target andcombat the invader, the innate immunesystem reacts non-specifically immediatelyupon infection, before adaptive immunityis triggered. When signaled, the body’scells respond to pathogens by secreting“cytokines,” proteins that function asmediators in the generation of an immuneresponse. Recent research has shown thatTLRs somehow recognize pathogens rightaway, activating the critical signaling path-ways that stimulate this initial immuneresponse. A number of new investigationsat UMMS–a representative few of whichare described in the following pages–aretargeted at understanding the mechanisms

by which TLRs recognize pathogens, howthey activate signaling pathways, and, ultimately, how TLRs can be manipulatedto limit or promote the immune response.

A developmental biologist, UMMSAssociate Professor of Molecular Medicineand Cell Biology, Y. Tony Ip, PhD, wasworking on the embryonic development

of the fruit fly when he became interestedin the Toll gene. First identified inGermany in 1980 as a gene in the pathwaythat controls dorsoventral patterning–thedevelopment of the fruit fly from the backto the belly–it soon became apparent thatthere were similarities between the Tollpathway in tiny fruit flies and a mam-malian pathway (the Interleukin 1Inflammatory Pathway) that was known to play a significant role in immunity. “Wefound that both pathways use a similarfamily of transcription factors [NF-kappaB],” said Dr. Ip. “So we asked, ‘Why is a transcription factor for inflam-matory gene expression and the regulationof T cells and B cells in mammals so simi-lar to a protein that controls dorsoventraldevelopment in Drosophila?’ ”

“...one hypothesis is that

the body needs some sort

of ‘danger’ signal, a signal

that activates the immune

response. Current research

indicates...Toll-like

receptors.”

– Neal Silverman, PhD (pictured left)

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Ip’s research focused on the Drosophilaequivalents of NF-kappaB (three fly genescalled, in the whimsical way of fruit flygene-naming, Relish, Dorsal and Dif) toanswer that question. “We started workingon the Toll-Dorsal pathway and we showedthat Dorsal was not only similar insequence to NF-kappaB, but it also func-tions in a similar way. In the fly embryo,Dorsal binds to sites that are akin to themammalian NF-kappaB signaling pathways,similarly regulating the genetic response that controls the developmental process as well as inflammation and immunity.”Subsequent investigations proved that allthree NF-kappaB-related proteins, Dorsal,Relish and Dif, play key roles in theDrosophila immune response. Toll, it was shown, was an important contributor to the fly’s immune response.

Ip is continuing his research into the Tollpathway to determine whether all of the Tollgenes in Drosophila (nine have been identi-fied in the fruit fly; 11 TLRs have been identified in mammals) play a role in theinnate immune response and also whetherthey have additional function in Drosophilabeyond immunity.

Like Ip, UMMS Assistant Professor ofMedicine Neal Silverman, PhD, is usingDrosophila as a model system to study themechanisms that allow pathogens to lead tospecific immune responses and to see what’sresponsible for transmitting a signal from thesite of infection to the nucleus of an immuneresponsive cell. “Immunologists have alwaysasked the question, ‘How does the body recognize something as being a pathogen so it knows to attack it?’” Dr. Silverman said.“It turns out there are a lot of differentanswers to that question, but one hypothesisis that the body needs some sort of co-stimu-latory or ‘danger’ signal, a signal that acti-vates the immune response. Current researchindicates that such signaling is most likelyaccomplished through Toll-like receptors.”

One model that Silverman is interested in isthe plague agent Yersinia pestis. Certain pro-

teins made by Yersinia can effectively stopthe innate immune response. “Yersinia canmake proteins and then when it infects amammal, it can nuzzle up to its cells andinject bacterial protein into them, at whichpoint it wreaks havoc. In particular, Yersiniamakes six of these proteins that get injectedand together they collaborate to effectivelystop the immune response,” Silvermanexplained. One of these proteins, in fact, has been shown to prevent the activation of NF-kappaB and the production of cytokines.To understand how this protein inhibits

the immune response, Silverman is examining how it blocks the signaling pathways to prevent the cytokine responseand is trying to determine what genes it istargeting in the Drosophila innate immuneresponse pathways.

“I think this is a really exciting area ofresearch in terms of possible clinicaladvances, bench to bedside,” saidSilverman, “That’s because a whole raft ofdiseases–some might even go so far as tosay all diseases–have in their pathology acontribution from the innate immune

Prior page: Neal Silverman, PhD, is poised before a series of images demonstrating the effects ofYopJ, a protein of plague agent Yersinia pestis, as manifested through the fruit fly eye (above).Through Drosophila’s optical instrument, Dr. Silverman is investigating the mechanism by whichYopJ can inhibit the immune response.

Tony Ip, PhD (above), is pictured against the illustration of the Drosophila Toll Pathway, which has been shown to play an important role in both the developmental process andimmunity. At right, cancer biologist Michelle Kelliher, PhD, is investigating the effect of protein RIP1, on the signaling of Toll-like receptors 3 and 4. Previously implicated in the signaling of tumor necrosis factor, an important pro-inflammatory cytokine affecting manyinflammatory diseases, Kelliher’s research has shown that RIP1 may also play an importantrole in innate immunity.

response—something that was not fullyappreciated just five or 10 years ago. Butwith the discovery of these Toll-like recep-tors, it’s really blossomed into a dynamicarea of research with the potential to haveimpact in a range of diseases.”

With cancer as one such potential disease,Michelle A. Kelliher, PhD, associate professor of cancer biology, has recentlyexpanded her own research into the TLRrealm. Dr. Kelliher’s research into TLRsdeveloped from a collaboration with JurgTschopp of Switzerland’s University of

Lausanne. Kelliher and Dr. Tschopp havebeen working on a protein (RIP1) that par-ticipates in the NF-kappaB response to thesignaling of TNF, or tumor necrosis factor,a cytokine that is produced by tumors andcontributes to muscle breakdown, weak-ness and loss of appetite in cancerpatients. TNF is also a very important pro-inflammatory cytokine affecting manyinflammatory and immune diseases. “It ishard to find a disease that TNF doesn’tinfluence,” Kelliher said.

Her studies indicate that RIP1 also existsin a pathway with Toll-like receptor 3 andpotentially, Toll-like receptor 4. “Thatprompted us to test whether TLR 3 or 4signaling is affected in mice that lack RIP1.We found that RIP1-deficient cells fail toactivate NF-kappaB or produce cytokineswhen exposed to molecules that typicallyevoke a response from TLR 3.” Continuingresearch is focused on exploring what happens to the signaling and to inflamma-tory gene expression in the absence ofRIP1. “While we previously thought thatRIP1 was a specific mediator for TNF only,we now see that it is also a mediator forTLR 3 and possibly TLR 4 and that it mayplay a very important role in regulatinginnate immunity.”

To further investigate these questions,Kelliher’s laboratory is working on developing a RIP1-deficient mouse model.“In the absence of RIP1 itself, mice don’tsurvive, so it’s an essential gene. We stilldon’t know why those RIP1-deficient micedie, but one idea that has developed fromTLR research is that the mice are very susceptible to infection because they cannot activate the cytokine response to pathogens.”

15

Although the innate immune system functions as a protective response,

an overactive response can be a detriment. One investigation studies TLR

response to a particular virus and the devastating effect inflammation can have.

16

Although the innate immune systemfunctions as an important protectiveresponse, the opposite–an overactiveimmune response–can be a detriment toorganisms. The manifestations ofcytokine production, such as intensefever, shock-like symptoms and inflam-mation, can prove dangerous and all toooften fatal. Evelyn A. Kurt-Jones, PhD,research associate professor of medicine,and Chair of Medicine Robert W. Finberg,MD, the Richard M. Haidack Professor ofMedicine, are investigating the mecha-

nisms associated with this overreactionof the innate immune response.

In studying TLRs, Dr. Kurt-Jones and colleagues recognized that viral diseasesoften had many of the same initial clini-cal features that are seen in a bacterialinfection such as fever and inflamma-tion. Their subsequent research foundthat TLRs did indeed recognize viralpathogens. “It turns out that a number ofviruses do engage Toll-like receptors andthis is important in ‘fighting-off’ an infection. However, while the inflamma-

tion associated with viral infection can be beneficial to the host, if that inflam-mation occurs in a closed compartmentlike the brain and skull it can actually be detrimental.”

One investigation underway is studyingTLR response to a particular virus and thedevastating effect that such inflammationcan have. “The herpes simplex virus 1(HSV 1) can cause a disease in neonatesand it has the clinical features of a shock-like syndrome,” Kurt-Jones explained. “In previous research, we

found that TLR 2 was involved in activa-tion of the immune response, so itoccurred to us that HSV 1 might alsoengage TLRs.” A series of studies con-firmed that HSV 1 did engage TLR 2 toprovoke an activation of cytokines.However, the cytokine activation was sur-prising. While mice with TLR 2 who wereexposed to the virus became infected andthe virus traveled into the brain–resultingin a massive inflammatory response,encephalitis and severe illness–mice with-out TLR 2 became infected, the virus went

into the brain, but they didn’t develop anyinflammation. “These mice survived andeventually the adaptive immune systemcleared the virus but without the inflam-mation. So, it was a distinct advantage tothose mice that didn’t have TLR 2. As longas you don’t have TLR 2 you can survivelong enough to make an adaptive responsethat will clear the infection.” These find-ings have led to clinical studies that areexamining the response of neonatal bloodcells to HSV which seems to indicate thatthese blood cells are more reactive to thevirus and have a much more exuberantcytokine response. “The eventual goalwould be to modulate or dampen the TLR2 response and prevent the encephalitis,”Kurt-Jones said.

Reflecting on the Toll and Toll-like receptor researchers currently at UMMS, Kurt-Jones noted that they are an invalu-able source of support and information.“We have frequent conversations through a recently established Innate ImmunityGroup. And, we have so many exceptionalpeople working on the many aspects of Tolland Toll-like receptors that we are becom-ing a major center for Toll research.”

As evidence of UMMS’ growing reputationin the field, Kurt-Jones joined colleaguesFinberg, Ip and Silverman with presenta-tions at Toll 2004, an international conference that attracted over 300 scientists from around the world. UMMSexpertise in TLRs was prominently fea-tured at the conference, which was co-organized by UMMS Professor ofMedicine Douglas T. Golenbock, MD. Arenowned TLR researcher and a leader in this emerging field, Dr. Golenbock alsopresented at the conference.

Kelliher looks forward to continuing workwith Toll-like receptors with the supportof the UMMS Toll community. “There issuch expertise to call upon here that weare all very excited about future researchin this area.”

Pictured with slides showing the inflammatory response triggered by the herpes simplex virus in the brains of infected mice, Evelyn Kurt-Jones, PhD, has demonstrated that the absence of Toll-like receptor 2 and the consequent lack of inflammation is actually beneficial to those mice.

A Place of Their OwnUMMS and its clinical partner gain space for conducting clinical research trials,

key to expansion and potential designation as a General Clinical Research Center.

By Alison M. Duffy

17

18

The newly opened Clinical TrialsUnit on the seventh floor of UMassMedical School is one of the more visiblecomponents of a concentrated multi-yeareffort by the Office of Clinical Research(OCR) to expand the clinical researchenterprise at UMMS in conjunction withits clinical partner, UMass MemorialHealth Care. While the Medical Schoolfocused considerable energies in creatinga successful and widely respected basicsciences research enterprise, the institu-tions’ clinical trials capabilities havelagged behind. That will soon change.

“Both the school and the clinical systemaspire to be one of the top ten academichealth centers and research medicalschools in the country, and if you look atthe top 20 or 30 now, they all have verystrong, very well developed clinicalresearch enterprises,” said John L.Sullivan, MD, director of the Office ofResearch and UMMS professor of pediatrics and molecular genetics &

microbiology. “Ours is really in its infancyand if we want to be an outstanding aca-demic health center and one of the top 25research medical schools in the country,our clinical research enterprise simply hasto be robust.”

Director of the Office of Clinical ResearchSheila B. Noone, PhD, notes that two of thefactors that faculty have said hamper theirefforts to grow the enterprise are a lack ofspace in which to conduct clinical studiesand a shortage of well-trained clinicalresearch nurse coordinators readily avail-able to staff those studies. Without thisessential support, Dr. Noone said,researchers often miss out on highly com-petitive clinical trials, particularly thosesponsored by industry that require immedi-ate start up. In answer to these needs,UMMS has invested $500,000 in the newClinical Trials Unit (CTU), which providesdedicated space, well trained staff and amenu of important services from whichclinical investigators can choose to help

expand, enhance and expedite high qualityclinical research studies.

The 2,600-square-foot suite is designedmuch like an ambulatory clinic, with fourpatient exam rooms for study visits, aninfusion room with two recliners, and aquiet, comfortable waiting room. It alsohouses a conference room, four staffoffices, and workspace and computersfrom which investigators and study coordinators can retrieve laboratoryresults and other necessary documents.The CTU also features a kitchenette and asmall laboratory with a centrifuge, a freez-er and a hematocrit machine, as well as anarea for packing and shipping of trial samples to comply with strict transportregulations. In addition, there is a securearea for study files and case reports and,working with the existing investigationalpharmacy located in the hospital, the CTUcan accept delivery of study drugs to beused during the day.

Prior page: Sheila Noone, PhD, and John Sullivan, MD, are a welcoming sight in the new Clinical Trials Unit. In the unit’s infusion room (below),four essential individuals who carry out key components of any clinical trial: (left to right) Lucie LaJeunesse, RPh (investigational pharmacist);Bernie White, RN (clinical research nurse coordinator); Donna Christian (regulatory specialist); and Michael Brennan (clinical contracts specialist).

19

Of particular value to the investigatorswill be the availability of highly skilledclinical research nurse coordinators, suchas Bernadette “Bernie” White, RN, CCRC,who serves as the CTU’s research manager. White, who oversees clinical trials for investigators in the currentClinical Research Center tucked away inthe hospital, is one of two full-time certified clinical research nurse coordina-tors who will staff the new CTU. The second coordinator is being recruited anda third per diem coordinator will beadded as the number of studies facilitatedby the CTU increases.

“The support of well-trained, experiencedresearch nurse coordinators is probablythe key to the CTU,” said Noone, whoholds a joint appointment as assistant professor in the Graduate School of Nursing and the Department of Obstetricsof Gynecology. “It’s time consuming forinvestigators to recruit and train their owncoordinators, especially for divisions inwhich there are sporadic trials. By staffingcoordinators, the CTU takes the recruitingand training onus off the researchers sothey can focus on the study and get itstarted quickly.”

“This is a different kind of nursing,”noted White, who has been a clinicalresearch nurse coordinator at UMMS since1989. These coordinators must have at least two years of research experienceand “an intimate knowledge of regulatoryinformation” in addition to skills in basiclife support, infection control, phleboto-my, EKG, IV insertion, and packaging andshipping of sensitive materials. While allareas of nursing require strict attention todetail and high quality patient care, Whitenoted that in research nursing, “you haveto be precise in not only what you do buthow you do it and how you document it, because the validity of the data can determine the outcome and the value of the research.”

Through the CTU, investigators canrequest coordinator support as either a “percent of effort,” depending on theintensity of the study, or on a per-visitbasis. Because some studies enroll asmall number of patients, or becauseinvestigators may need assistance withonly one part of their study, the coordinators can simultaneously managestudies for several different investigators.Fees for the services are factored into thestudy budget.

Peter N. Riskind, MD, PhD, professor ofclinical neurology, is one such investiga-tor who expects to utilize the CTU’s a lacarte menu. He already relies on White toadminister a novel, once-a-month infusionof a study drug to treat multiple sclerosis,something Dr. Riskind has neither the clinic space nor the staff time to accom-plish. He agrees that the CTU’s flexibilitywill serve a critical need: “We can add tri-als easily knowing that through the CTUwe will have the space and the coordina-tor available.” In Riskind’s experience, aCTU “offers tremendous time savings interms of streamlining paperwork and lin-ing up knowledgeable staff, and can get us

to a study’s starting line much morequickly. It helps to not have to hire andtrain someone for each trial.” Riskindnotes that with enough space and appro-priate coordinator support, he and his col-leagues “could double the number of clin-ical trials we’re doing in neurology.”

Aside from physical space and staff time,the services offered by the Office ofClinical Research include the support ofan investigational pharmacist, LucieLaJeunesse, RPh, who also serves as vicechair of the Institutional Review Board(IRB). LaJeunesse consults with clinicalresearchers, reviews new study protocols,manages the dispensing of investigationaldrugs and handles drug-related documen-tation. Investigators also benefit from regulatory support—help with the some-times overwhelming but important crossing of t’s and dotting of i’s during themany steps preceding the start of any clinical trial. The negotiation of contracts,budgeting process and, in particular, theIRB submission process, can be onerous,according to Noone, especially for investi-gators who have busy clinic schedulesand are managing concurrent clinical

The new Clinical Trials

Unit provides dedicated

space, well trained staff

and important services

from which clinical

investigators can expe-

dite high quality clinical

research studies.

trials. Donna Christian, the CTU’s on-siteregulatory specialist, is available to assistclinical investigators with study initiationby drafting their IRB submission and con-sent form, organizing their regulatory doc-uments for the sponsor, and, if needed,assisting with the investigational newdrug applications to the FDA.

In the past two years, Christian has sup-ported 38 investigators in 55 projects.Departments that have sought regulatoryor research coordinator assistance fromthe Office of Clinical Research includeneurology, pediatrics, dermatology,endocrinology, gastroenterology, radiologyand psychiatry, indicating an across-the-board need for the CTU.

“2004 saw the number of industry-spon-sored clinical trial agreements nearly double, to 114,” said Noone, thanks to theoffice’s concerted efforts to streamline theprocess of review and negotiation of clini-cal trials agreements. (In comparison, theaverage number of trials opened from1995 to 2003 was 64 per year.) Noonedeveloped a new database to track theprocess of contract receipt, review andnegotiation that is proving invaluable inreducing the time that will be needed toprocess an agreement to two or threeweeks instead of the months it currentlytakes. She is assisted in the communica-

tions and negotiation of industry-spon-sored clinical trials by Michael Brennan,clinical contracts specialist for the Officeof Clinical Research.

Cognizant that clinical trials units at otherinstitutions have struggled with an overwhelming response by theirresearchers–about three-quarters of academic medical centers in the UnitedStates have opened similar units in thelast several years, according toCenterwatch, a clinical trials listing service–Noone plans to carefully managethe growth of the CTU. Seven to ninestudies will move to the CTU this fall, and Noone projects approximately 25 to30 clinical trials will utilize the unit in itsfirst year while also providing relevanttraining for faculty.

“There’s an education and training com-ponent that I feel very strongly about,” shesaid. “By training faculty to prepare moreaccurate study proposals and understandthe budgeting process a little better, wecan be more efficient in the start up of tri-als, thereby increasing the number of trialswe can manage.” Noone has presented tofaculty several sessions on budget planning and regulatory issues and is currently planning one on industry-spon-sored clinical trials with representativesfrom the Mass Biotech Council. She also

hopes to have an FDA representative present a session on the regulatory issuesregarding device studies.

One final component Noone wishes todevelop through the CTU is a useful poolof study volunteers, which would requiretwo things: raising public awareness aboutwhat participation in a clinical trialentails, and a workable database of volun-teers, particularly for healthy studies.Many clinical studies recruit patients whosuffer the disorder being studied, but thereis an increasing need for healthy people in phase 1 trials, something a volunteer database could facilitate.

In providing an array of services, Nooneand Dr. Sullivan expect the CTU to serveclinical researchers from across the entireinstitution, enabling faculty to pursuemore National Institutes of Health-spon-sored clinical research studies and eventu-ally positioning UMMS and UMassMemorial for a successful application fordevelopment of a General ClinicalResearch Center. According to the NIH,there are currently 78 such centers at uni-versity-based hospitals in the country,facilities that offer centralized and highlyspecialized resources for inpatient andoutpatient clinical research. Right now,Sullivan said, UMMS stands out among itspeer institutions for not housing a center.

“While we’ve been extraordinarily suc-cessful in developing a rich talent pool inthe basic sciences, physician-scientists area rare breed and very difficult to attract,”he said. “One would expect to see a morerobust clinical research facility here, akinto the vibrant basic science work currentlyunderway. With the consensus amongleadership in both institutions, that’s whatour efforts are now directed toward.”

“I believe we have the pieces in place,”agreed Noone. “With the collaboration ofthe Medical School and its clinical part-ner, we are primed to elevate the scale,scope and complexity of the clinicalresearch enterprise across our campuses.”

20

“We have the pieces in

place. We are primed to

elevate the scale, scope and

complexity of the clinical

research enterprise across

our campuses.”

– Sheila Noone, PhD

21

Grants and Research

BIOCHEMISTRY

& MOLECULAR PHARMACOLOGY

National Institutes of Health

Job Dekker, PhD, assistant professor:Structural Annotation of the HumanGenome, one year, $366,820; recommend-ed for two more years, $800,000.

Kai Lin, PhD, assistant professor:Structural Basis of Regulation of IRF, oneyear, $383,340; recommended for threemore years, $1.2 million.

C. Robert Matthews, PhD, the Arthur F.and Helen P. Koskinas Professor ofBiochemistry & Molecular Pharmacologyand chair: Folding Mechanisms of TIMBarrel Proteins, $344,475; recommendedfor three more years, $1 million.

William E. Royer, PhD, associate professor: Ultrafast Time-resolvedCrystallography on Scapharca Hb, oneyear, $227,724; recommended for threemore years, $651,000.

Scot A. Wolfe, PhD, assistant professor:Dimeric Cys2His2 Zinc Finger Proteins forGene Targeting, one year, $274,003; recommended for four more years, $1.2 million.

Zuoshang Xu, MD, PhD, associate profes-sor: Understanding Mechanism andTherapy of ALS Using RNAi, one year,$367,688; recommended for four moreyears, $1.5 million.

CANCER BIOLOGY

National Institutes of Health

Dario C. Altieri, MD, the Eleanor EustisFarrington Chair in Cancer Research andchair: Control of Apoptosis in Cancer bySurvivin, one year, $298,920; recommend-ed for four more years, $1.2 million.

CELL BIOLOGY

National Institutes of Health

Harvey M. Florman, PhD, professor:Regulators of the Sperm AcrosomeReaction, one year, $343,000; recommend-ed for four more years, $1.3 million.

Timothy Henion, PhD, research assistantprofessor: Notch Signaling in OlfactoryProgenitor Cell Fate, one year, $141,500;recommended for one more year,$141,500.

Andre J. Van Wijnen, PhD, associate pro-fessor: Bone Cell Growth Regulation byRunx2/Cbfal, $293,374; recommended forfour more years, $1.1 million.

FAMILY MEDICINE & COMMUNITY

HEALTH

Department of Health and

Human Services

Darlene M. O’Connor, PhD, associate pro-fessor: Real Choice Systems Change, threeyears, $499,992.

Carole C. Upshur, EdD, professor:Treatment of Chronic Pain—Consumerand Provider Concerns, one year,$100,000.

MEDICINE

National Institutes of Health

Elliot J. Androphy, MD, the Barbara and Nathan Greenberg Chair inBiomedical Research: Functions of HumanPapillomavirus E6, one year, $293,355;recommended for four more years, $1.2 million.

Egil Lien, PhD, assistant professor: TheRole of LPS and Toll-like Receptors inPlague, one year, $382,160; recommendedfor four more years, $1.5 million.

Shan Lu, MD, PhD, associate professor:Multi-gene Plague Vaccine With ExpandedProtection, one year, $550,179; recom-mended for one more year, $540,000.

Aldo A. Rossini, MD, the William andDoris Krupp Professor of Medicine:Interdisciplinary Studies of HormoneFunction, one year, $248,054; recommend-ed for four more years, $1.3 million.

Neal Silverman, PhD, assistant professor:Activation of Insect Immunity by Gram-negative Bacteria, one year,$357,750; recommended for four moreyears, $1.4 million.

Michele Trucksis, PhD, MD, associate professor: Accessory Cholera Enterotoxin,Mechanism of Action, one year, $119,250;recommended for three more years, $1.1 million.

Robert B. Zurier, MD, professor:Treatment of Rheumatoid Arthritis—Marine/Botanical Oils, one year, $551,061;recommended for three more years, $2.2million.

MOLECULAR GENETICS

& MICROBIOLOGY

National Science Foundation

Dannel McCollum, PhD, associate professor: Regulation and Function of Clp 1p Protein Phosphatase, one year,$283,713; recommended for three moreyears, $800,000.

MOLECULAR MEDICINE

American Diabetes Association

Laxman D. Gangwani, PhD, research assis-tant professor: To Define the Function of theZinc Finger Protein ZPR1 in SpinalMuscular Atrophy, one year, $110,805; rec-ommended for two more years, $223,000.

New and competitive renewal grants of $100,000 or more are listed here according to department and funding sources.

22

Grants and Research

National Institutes of Health

Joel D. Richter, PhD, professor:Polyadenylation and TranslationalControl, one year, $339,962; recommend-ed for three more years, $1 million.

Rossella G. Tupler, MD, PhD, researchassistant professor: Investigating theMolecular Basis of FSHD, one year,$367,688; recommended for four moreyears, $1.5 million.

U.S. Army

Stephen J. Doxsey, PhD, associate professor: Centrosome-based Mechanisms,Prognostics and Therapeutics in ProstateCancer, three years, $596,250.

Keith W. Mikule, PhD, a postdoctoral fel-low in the laboratory of Stephen J. Doxsey,PhD, associate professor: Building BreastCancer: Dissecting the Contribution ofPericentrin and its Binding Partners toChromosome Instability andTumorigenesis, three years, $171,000.

NEUROBIOLOGY

National Institutes of Health

Vivian G. Budnick, professor: TheWingless Transduction Pathway inSynapse Development, one year, $321,975;recommended for four more years, $1.3 million.

Patrick Emery, PhD, assistant professor:Circadian Photoreception in DrosophilaMelanogaster, one year, $291,946; recommended for four more years, $1 million.

Steven M. Reppert, MD, the HigginsFamily Professor of Neuroscience andchair: Circadian Clock: TranscriptionalControl, one year, $367,688; recommend-ed for three more years, $1.1 million.

Scott Waddell, PhD, assistant professor:How Does the Amnesiac Gene ProductAid Memory, one year, $315,993; recom-mended for four more years, $1.3 million.

NEUROLOGY

National Institutes of Health

William Schwartz, MD, professor:Neurobiology of Circadian Dysrhythmias,one year, $294,150; recommended forthree more years, $882,000.

PATHOLOGY

National Institutes of Health

Kenneth L. Rock, MD, professor and chairof pathology: Immunobiology CTLResponses to Exogenous Antigens, oneyear, $403,125; recommended for fourmore years, $1.2 million.

Richard and Susan Smith

Family Foundation

Francis K. Chan, PhD, assistant professor: Smith Family New InvestigatorAward; TNF-Induced Programmed Cell Death in Immune Responses, two years, $200,000.

PEDIATRICS

National Institutes of Health

Peter E. Newburger, MD, professor: GeneExpression in Mature Neutrophils, oneyear, $562,035; recommended for fourmore years, $2.4 million.

U.S. Department of Education

Charles D. Hamad, PhD, associate professor: Fund for the Improvement of Postsecondary Education, one year, $149,864; recommended for two more years, $300,000.

PHYSIOLOGY

National Institutes of Health

John V. Walsh, MD, professor: Local Ca2+Signaling in Smooth Muscle, one year,$465,542; recommended for four moreyears, $2 million.

PSYCHIATRY

Alzheimer’s Association

Evgeny I. Rogaev, PhD, professor:Interaction Between Presenilin-related Putative Proteases and Alzheimer’s Disease Pathway, three years, $250,000.

National Institutes of Health

Timothy Q. Duong, PhD, assistant professor: Layer-Specific Functional and Perfusion Imaging of Retina, one year, $344,475; recommended for threemore years, $1 million.

Karen Lionello-Denolf, PhD, assistant professor: Developing a Model of Transitive Behavior, one year,$127,350; recommended for one more year, $127,350.

SURGERY

U.S. Army

Shuk-mei Ho, PhD, professor: Estrogen Receptor-beta Hypermethylationand Prostate Carcinogenesis, three years, $596,251.

Alumni Report

Do you recall your Commencement? Can you picture UMMS biomedical research at that time? We were justifiably proud of ourachievement. We were delighted to boast researchers of the highest

caliber and graduate students whose work was at the leading edgeof research. Our students and faculty were capturing national atten-tion for their research. Fifteen years ago, the Program in MolecularMedicine was just an emerging idea. The Graduate School ofBiomedical Sciences had grown to recruit 25 students annuallyand our alumni had almost reached 100.

Fast forward to Commencement 2004 and the growth is trulyastonishing! Entering our 25th year of the GSBS, we now recruitmore than 80 students annually. We number more than 250 alumni. Our school stands at 350 students and 250 research faculty.We house half of our faculty and students in a new, state-of-the-art,360,000-square-foot research building and our basic scienceresearch program is ranked 18th among the nation’s medicalschools. The numbers speak volumes but only begin to capture theexcitement that circulates about our school. We feel this excitementin many ways. Our students eat, drink and breathe their research.They work long hours to drive their progress forward, ever awarethat their competition is close at their heels. Our students under-stand the importance of their work and are determined to experi-ence the thrill and recognition of bringing their discoveries to pressfirst. We encourage this attitude and celebrate each success theyenjoy. More significantly, our students understand that every inchof progress brings new hope to those whose health is inexorablylinked to research success and they are determined to succeedwhere others have not.

Each mid-winter heralds the annual GSBS recruitment weekends.Here, prospective students experience our collective excitement forgraduate studies. Faculty, students and staff organize and execute aweekend of science, interviews, education and social mixingwhich, for all participants, captures the essence of the GSBS—col-legiality, passion for research, ambition, teamwork, unquenchableintellectual curiosity, competition, friendships, hard work and fun!These qualities encapsulate the graduate experience which, whencombined with a nurturing hand from one or more of our giftedfaculty, transforms talented undergraduates into the scientific lead-ership of tomorrow.

For the researcher, the ultimate measure of an institution isthe quality of the research that bears the institution’s name.

The quality, diversity and impact of the research carried outby GSBS students and their guiding faculty over these 25 yearsis stunning. We are recognized at the highest levels of peerreview for our contributions to the areas of diabetes, AIDS,RNA interference, cancer, immunology, neuroscience and neu-rodegenerative disease, to name just a few. This success hascatalyzed further recruitment of outstanding new faculty andgraduate students to the school. We have the overwhelmingsense that our work and growth have only just begun.

We have risen to national distinction through the efforts of many atall levels of this institution. The leadership team of my office andthe chairs has worked to foster an environment that promotes bio-medical research and the development of tomorrow’s scientificleaders. We are thrilled by the success that our junior faculty andgraduate students enjoy today and we continue to work diligentlyto promote an environment in which research can flourish.

As we look to the future with a sense of accomplishment and inanticipation of exciting discoveries and growth yet to come, weshould also recognize the great debt we owe our founding facultywho include the first dean of the graduate school, George Wright,and his successor, Thomas Miller Jr. Each shaped this school andcultivated an environment in which faculty and students canthrive. If I may quote the current dean of the GSBS, AnthonyCarruthers, “The first 25 years have produced astounding achieve-ment by our school. The next 25 years will be breathtaking.”

Aaron Lazare, MD

MESSAGE FROM THE

CHANCELLOR/DEAN

23

Alumni Profiles

Dr. Alla Grishok was in the right place at theright time. A graduate student in the UMassMedical School laboratory of Craig C. Mello,PhD, Howard Hughes Medical InstituteInvestigator and the Blais University Chair inMolecular Medicine, Grishok was involved inmany of the first investigations that unlocked thepossibilities of RNA interference (RNAi), one ofthe most important methods used in cutting-edgebiomedical research today.

Yet Grishok almost didn’t attend UMMS. Withher bachelor’s degree in molecular biology fromKiev State University, Grishok worked for adecade as a research assistant in her nativeUkraine and as a research technician at theMedical College of Wisconsin before deciding topursue her PhD. Admitted into the GraduateSchool of Biomedical Sciences (GSBS) in 1995,she says that if she hadn’t entered the program,she probably wouldn’t have gone back to schoolfor her doctoral degree at all.

“I chose the GSBS because it was flexible andoffered more interdisciplinary opportunities. I was also very interested in the work beingundertaken at the time in Jeanne Lawrence’s laboratory on regulatory RNAs. I was fortunatethat, although there were no opportunities in Dr.Lawrence’s lab, I was able to find out more aboutDr. Mello’s lab from a student, Sam Driver, whois actually one of the authors on the originalRNAi paper published in Nature.”

Although graduate school was difficult–giventhat she was a single parent pursuing her degreelater in life–Grishok credits her success at theGSBS to the warm environment and constantsupport she received from her fellow studentsand the administration.

Currently a postdoctoral fellow at the Center forCancer Research at MIT, Grishok is pursuing herpassion for genetics and microRNAs in C. ele-gans—work she directly attributes to her experi-ence in Mello’s lab. In recognition of her out-standing research, she was named one of 17recipients of the 2002 Weintraub GraduateStudent Award by the Fred Hutchinson CancerResearch Center, and was awarded a three-yearDamon Runyon Cancer Research Foundationpostdoctoral fellowship, presented to young sci-entists whose research focuses on cancer preven-tion and therapies.

“It’s rare to have the opportunity to do work in afield that is just developing,” Grishok said.“When I look back on our discussions of the firstmutants identified in the RNAi pathway, it’s likea miracle. If I had pursued a different path, Iwould definitely have been less successful in myown research. The GSBS allowed me to workindependently and design my own experiments.And, that’s why I went to graduate school—toformulate my own scientific questions and tofind answers.” —LCB

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Alla Grishok, PhD ’01

Kenneth Wright, PhD ’90

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Dr. Kenneth Wright is gratified to be conductingcutting-edge cancer research at a prestigious insti-tute, in his home state, no less. The GSBS gradu-ate is Member-in-Residence at the H. Lee MoffittCancer Center & Research Institute, located on thecampus of the University of South Florida (USF)in Tampa—the youngest institution ever to receivecomprehensive National Cancer Center accredita-tion from the National Cancer Institute.

Wright’s journey to the forefront of cancer biolo-gy has taken him full circle professionally aswell as geographically. His current, NIH-fundedinquiries into how the immune system can beharnessed to fight tumors build on his firstexplorations into how cells work in the lab ofGary Stein, PhD, and Janet Stein, PhD (both thenat the University of Florida, now at UMMS asthe Gerald L. Haidak, MD, and Zelda S. HaidakProfessor of Cell Biology and chair, and profes-sor of cell biology, respectively).

Wright was an undergraduate at the University ofFlorida when he first met the Steins; he pro-gressed from volunteering in their lab, to com-mencing doctoral studies there. When Gary Steinwas invited to become chair of cell biology atUMMS in 1987, Wright also made the move. “Itwas a great opportunity and an easy decision.UMMS already had a strong reputation.”

His decision to focus on cancer research wascemented after Wright completed a post-doctoralfellowship with Jenny Ting, PhD, at the

Lineberger Comprehensive Cancer Center at theUniversity of North Carolina. Today Wright isassistant professor of interdisciplinary oncologyin the immunology program at the Moffitt CancerCenter. His inquiries into the normal and abnor-mal function of immune cells led to his lab’sbreakthrough discovery of a key moleculerequired for the development of cancer-fightingimmune cells. The molecule modifies histone pro-teins—the same proteins he studied as a studentat the GSBS. “Having histones on my radarhelped in our discovery.”

Wright’s commitment to training the next genera-tion of scientists has evolved along with hisresearch. He again credited the Steins’ influence.“They have a love for science and they make itfun. They taught me that mentoring students is avery important part of what we do.” In responseto the shortage of trained investigators in the still-young field, Wright was instrumental in establish-ing a Cancer Biology PhD Program at Moffitt andUSF. “Our students start learning about cancerfrom day one. Scientific discovery takes time. Ourjob is to keep working at it so the breakthroughswill keep coming.”—SLG

According to Dr. Daniel Hebert, “life just doesn'tget any better.” With the support of enthusiasticstudents and sufficient grant funding, the associ-ate professor of biochemistry & molecular biolo-gy at the University of Massachusetts Amherst ispursuing his own research riddles. And, he cred-its his experience at the Graduate School ofBiomedical Sciences (GSBS) with leading him toembrace this career choice. “In academia, youcan truly formulate your own scientific questionsand engage in investigations specifically gearedtoward answering those questions,” he said.

Hebert currently oversees a research group with-in the UMass Amherst Program in Molecular andCellular Biology, monitoring how proteinsmature and degrade in the cell. “When proteinsdon’t fold correctly, it can lead to a number ofdisease states,” Hebert said, “Our lab investigatesthis chemical question in the context of livingcells, focusing on the factors that assist theseprocesses. Although very basic biology, its con-nection to disease is evident.”

Following receipt of his bachelor’s degree inchemistry from the University of NewHampshire, Hebert worked for a year in his fami-ly’s business, which manufactures ion-selectiveelectrodes. However, his brother’s positiveimpressions of UMMS while a student at nearbyWorcester Polytechnic Institute, coupled withHebert’s own interest in the biological sciences,led him to the GSBS.

Still in its infancy in 1985 when Hebert enteredthe program, the GSBS was preparing to graduateits first students. One of a dozen in his class,Hebert noted the closeness among students–whoall knew and supported each other–as well asthe immediacy with which he was able to pursuehis interest in biochemistry. Hebert worked asthe first member in the newly formed lab ofAnthony Carruthers, PhD; the current GSBSDean was then a junior investigator who had justcompleted his own postdoctoral experience. “Itwas a very attractive program; you were able tofocus on your research from the get-go. After myfirst lab rotation, I co-authored a paper withTony Carruthers,” noted Hebert. “We had incred-ible access to the faculty.”

Following receipt of his PhD, Hebert pursued hispostdoctoral work in the Department of CellBiology at Yale Medical School. Like his experience at UMMS, the spirit in his lab wascommunal. And, it’s this type of environment–one that Hebert continues to foster today–that gar-ners fruitful results. “The stereotype of the scien-tist as introverted couldn’t be farther from thetruth,” concluded Hebert. “Researchers must bestrong communicators, willing to interact with col-leagues. It’s collaboration that leads to success inscience; no one individual can do it alone.” —LCB

Daniel N. Hebert, PhD ’92

Alumni Profiles

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Alumni of the School of Medicine, Graduate School of

Biomedical Sciences and the Graduate School of Nursing may

send their latest news to alumni@umassmed.edu

1975

Claudio Delise, MD, no longer practices obstetrics, but continueshis work in the field of gynecology. He and his wife, Joan, arerelocating to Sudbury, Mass. from Hingham and are enjoyingtheir 20-month-old grandson.

1979

Robert M. Haddad, MD, was appointed president and chiefexecutive officer of Caritas Christi Health Care in May, after serv-ing since 2001 as president of Caritas St. Elizabeth’s MedicalCenter in Boston, a teaching hospital affiliated with Tufts Schoolof Medicine and the Caritas system’s flagship institution.

1982

David Liberman, MD, is president and founder of ComputerTrust Corporation of Boston, which develops, installs and sup-ports the WinSURGE family of information systems used in hos-pitals and commercial laboratories performing anatomic patholo-gy (surgical pathology, cytology, autopsy, histology and nuclearmedicine). Dr. Liberman lives in Brookline, Mass. with his wife,Judy, and their daughters, Cindy, 10, and Debbie, 7.

Bruce D. Minsky, MD, recently received an honorary medicaldegree from the Friedrich Alexander University in Erlangen,Germany. He is a professor of radiation oncology in medicine atthe Weill Medical College of Cornell University, as well as thevice chairman of the Department of Radiation Oncology andchairman of Quality Assessment at Memorial Sloan-KetteringCancer Center. His wife, Connie Kissinger, is a vocalist inHawaii; the couple lives in Manhattan and Kauai.

1989

Susan C. Schiavi, PhD, is a principal scientist leading a discov-ery team at Genzyme Corp. of Framingham, Mass. Dr. Schiavicompleted her post-doctoral work at Harvard Medical School.She lives in Hopkinton with her husband, David S. St. Laurent,MD ’85, and their son and daughter.

Gregory A. Taggert, MD, has joined UMass Memorial MedicalCenter as chief of the Foot and Ankle Program in the Departmentof Orthopedics & Physical Rehabilitation. Dr. Taggert has alsobeen appointed assistant professor of orthopedics & physicalrehabiliation at UMMS. Most recently he practiced at the Centerfor Orthopaedics of New Haven, Conn., and served as an assis-tant clinical professor of orthopedics and rehabilitation at YaleUniversity School of Medicine. A major in the U.S. ArmyReserve, Dr. Taggert has been deployed in Bosnia, Afghanistanand Kuwait, and recently returned from deployment in Iraq.

1990

Dmitry Blinder, PhD, is president of ViroGen Corporation ofWatertown, Mass., a manufacturer of recombinant viral anti-gens and monoclonal antibodies for research and diagnosticapplications. Dr. Blinder is a recipient of the U.S. CivilianResearch & Development Foundation’s “Next Steps to theMarket” Program Awards for the development of a biotechnology group for the production of MonoclonalAntibody Kits and the New Approach for Modulation CD-95-Mediated Apoptosis. Dr. Blinder resides in Boston and is onthe faculty of Northeastern University.

2000

Geneve Allison, MD, is in her first year of a fellowship in infec-tious diseases at Tufts-New England Medical Center, after serv-ing her internal medicine residency at Alameda County MedicalCenter in Oakland, California. She writes: “I live in Malden,Mass. with the greatest guy ever, my husband, Michael Murphy.We were married on November 28, 2003, in California. KatharineCornell, MD ’00, and her husband, Daron, and daughter, Lucy,braved the 3,000 mile trip to celebrate with us. I would love tohear from folks—gallison@tufts-nemc.org.”

Adam Feldman, MD, and his wife, Jennie Kroopnik Feldman,are the proud parents of a new baby boy who has been namedafter Adam’s late father, Robert Feldman.

Jeffrey B. Hopkins, MD, has joined the medical staff of Milford-Whitinsville Regional Hospital. While in residency training atUMass Memorial Medical Center, Dr. Hopkins served as a LifeFlight physician.

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Class Notes

1983Susan Auerbach-Ferdman, MD, is joined by her husband, Mauro, and daughter, Dina, at an August Parents’Orientation at UMMS. Dina is a first-year medical student. Dr.Auerbach-Ferdman practices in Winchester, Mass. and resideswith her family in Cambridge.

The Last Word

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By Thomas Manning, Deputy Chancellor for Commonwealth Medicine and Strategic Facilities

Planning, and Timothy Fitzpatrick, Associate Vice Chancellor for Master Space Planning

When you combine thenumber of years we’veworked here, it totals morethan 50; yet, we have neverbeen more enthusiasticabout the campus’s progressthan over the last two. Themulti-faceted projects thatcomprise the strategy to

modernize the campus–replacement of the main building’s granitefaçade with limestone and a new window system; the constructionof new lobbies and entrances for the Medical School and hospital;construction of the Clip-On office addition; reconstruction of theFaculty Conference Room; the enclosure of the Chancellor’sCourtyard; and a new parking garage and a 256,000-square-foothospital addition, including a new Emergency Department–areexciting, and yes, immensely challenging. But as we see limestoneand glass replace the granite façade, we are invigorated by thechange from a gray, aging facility to a light, bright building.

In recent months, construction of the hospital entrance andlobby has accelerated and the new Medical School lobby hastaken shape. Visitors to the campus will be able to quickly recog-nize the hospital and school, whose entrances have, seen now inretrospect, been rather obscure over all of these years. With two-story configurations, the lobbies distinguish main entrances thatare appropriate for a nationally recognized medical school andhealth care leader. Furthermore, the shared elements of theentrances will reinforce that UMass Medical School and UMassMemorial are united in partnership, while the subtle design dif-ferentiation will distinguish the organizations as entities withindividual, yet complementary missions.

One of the most gratifying elements of Campus Modernization hasbeen the cooperation shown by faculty, staff and the visiting pub-lic. Their remarkable patience and good cheer in the face of exten-sive construction and, at times, disruption without any immediatebenefit, is a tribute to our institutional culture and the people weserve. Yet, we are now approaching the time when the benefitswill begin to be revealed. With the opening of the new garage thisfall, employees who were shuttled from off-site locations havereturned to parking on campus. Congestion on campus roadways

has decreased, and our Office of Public Safety is now positioned atthe front of the new garage facing South Road, our most heavilytraveled thoroughfare, to underscore our commitment to safety.

The new year will bring additional benefits. Addressing a criticalshortage of space, Campus Modernization will give us the opportunity to add valuable conference rooms and offices. With the completion of the Clip-On, a number of smaller conferencerooms will provide teaching venues in demand from all threeschools, while medium and large rooms will meet a variety ofadministrative and instructional needs. In addition to creating twoconference rooms, the enclosure of the Chancellor’s Courtyard willenlarge the Chancellor’s Office operating area and will allow Dr.Lazare to bring additional senior staff into the vicinity, enhancingboth functionality and communication. And, although its foot-print won’t have changed, the essential Faculty Conference Roomwill feature significant structural, organizational and audiovisualimprovements. To reinforce its functionality, the room is also beingconstructed in such a way that it can be opened up into the newMedical School lobby for large events.

We have grown so much and so quickly over the years that theorganization, signage and greenery on campus has suffered. At thecompletion of various phases of Campus Modernization, we lookforward to bringing a greener environment to our shared con-stituencies. Moreover, a comprehensive signage program will beimplemented in phases to make traveling on and through campussafer and easier.

To top it off, as the UMass Memorial Lakeside Expansion takesshape on the east side of campus, it is thrilling to witness our clinical partner’s continued investment in quality patient care and education through the introduction of a state-of-the-art technological infrastructure.

While Campus Modernization progresses and meets some of theimmediate needs of our institutions, it is imperative that we con-tinue planning additional initiatives for enhancement of theWorcester campus. By January 2005, we expect to have in handan updated campus master plan that addresses our future infra-structure and programmatic needs and identifies areas of growththat will contribute to our continually energized academic andclinical enterprises.

For the past two years, the UMass Medical School community has come to embrace the challenges and opportunities of Campus Modernization—a four-year initia-

tive to revitalize and renovate the Medical School’s main campus in Worcester. With the approach of the half-way mark in the schedule of projects, Thomas Manning

(below, left) and Timothy Fitzpatrick offer their perspectives on the success of Campus Modernization to date and the vision for future growth on campus.

the magazine of the University of Massachusetts Medical School, one of five campuses in the UMass system. The magazine is distributed three times a year to members, benefactors and friends of the UMMS community. Published by the Office of PublicAffairs & Publications and paid for out of non-state funds.

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