Annual Report 2012 - Buck Institute

Through a remarkable convergenceof events, the Buck Institute forResearch on Aging is now positionedto take a central role in addressingthis global health crisis.

The time has come for theBuck Institute to fulfill itsfounding promise to increasehealthspan—the healthy yearsof human life.

4 Buck Institute 2012 Annual Report

the time has come2012 annual reportThe Buck Index 2012 ............. 6Letter from the President ......... 8Letter from the Chair ............. 9Going Global . . . . . . . . . . . . . . . . . . . 10Year in Review .................. 16Accomplishments ............... 24Postdoc Collaborations .......... 26Geroscience .................... 34Faculty Profiles . . . . . . . . . . . . . . . . . 36Board of Trustees ............... 43Scientific Advisory Board ........ 43Buck Advisory Council . .......... 44Financial . ....................... 45Honor Roll of Donors ............ 48Buck Institute 2012 Annual Report 5

the buck index 2012Number of people worldwide who will be age 65 and older by 2030: 1 in 81Growth rate of older populations in developed countries between 2010 and 2050: 71%growth rate in less developed countries: 250%2Percentage of older Americans living with one chronic condition: 80%percentage living with at least two: 50%3Portion of United States’ health care costs used to treat chronic diseases: two-thirds4Percentage of older Americans’ health care costs spent to treat chronic diseases: 95%5Percentage that the lifespan of healthy nematode worms is extended when exposed to Thioflavin T,a common laboratory dye: 50%6Rank of the United States of per capita health expenditures in the world: 17Chance that an American age 65 or older has Alzheimer’s: 1 in 88Expected increase in Alzheimer’s disease costs in the United States between 2011 and 2050:$183 billion to $1.1 trillion9Percentage that weekly moderate exercise reduces the risk of developing breast and colon cancers: 21–25%10Chance that a woman in a high-income country is sufficiently active: 1 in 211Percentage of Americans age 65 and older who did not exercise in the past month: nearly 32%12Percentage of all American cancer cases diagnosed in people age 55 and older: 77%131 National Institute on Aging. “Overview: Our Aging World.” Why Population Aging Matters: AGlobal Perspective.2 National Institute on Aging. “Humanity’s Aging.” Global Health and Aging.3, 19 National Center for Chronic Disease Prevention and Health Promotion, Division of Adultand Community Health. “At a Glance 2011” Healthy Aging: Helping People to Live Long andProductive Lives and Enjoy a Good Quality of Life.4, 5, 12 Centers for Disease Control and Prevention and the Merck Family Foundation. TheState of Aging and Health in America 2007.6 Alavez, Silvestre, et al., “Amyloid-binding Compounds Maintain Protein Homeostasis DuringAgeing and Extend Lifespan.” Nature 472 (2011): 226–229.7 World Health Organization. World Health Statistics 2012. (Geneva, Switzerland: World HealthOrganization, 2012).8, 9 Centers for Disease Control and Prevention. The CDC Healthy Brain Initiative: Progress2006–2011. (Atlanta, GA: Centers for Disease Control and Prevention, 2011).10, 11, 16, 21, 22, 24 World Health Organization. Global Status Report on NoncommunicableDiseases 2010. (Geneva, Switzerland: World Health Organization, 2011).6 Buck Institute 2012 Annual Report

the buck index 2012Lifetime risk of developing cancer for an American man: 1 in 214Lifetime risk of developing cancer for an American woman: 1 in 315Percentage of cancers that can be prevented by improving diet, physical activity, and body composition:27–39%16Percentage that Buck CEO Brian Kennedy believes laboratory research will extend the human healthspan: 15%17Expected percentage of Americans living with cardiovascular disease in 2030: 41%18Percentage of deaths caused by heart disease in Americans age 65 and older: 28%19Frequency that an American dies from a coronary event: one every minute20Number of deaths that could be prevented each year worldwide if salt consumption were reduced to recommended level:2,500,00021Percentage of the world’s adults who are overweight: 35%22Percentage of Americans age 65 and older living with diabetes: 27%23Percentage that engaging in weekly moderate physical activity reduces the risk of developing diabetes: 27%24Percentage of the world’s blind people who are age 50 and older: 82%25Percentage of visually impaired people who live in developing countries: more than 90%26Percentage increase in the lifespan of nematode worms when treated with lithium: 46%27Percentage that rapamycin extends lifespan in mice: 12%2813, 14, 15 American Cancer Society. Cancer Facts & Figures, 2012. (Atlanta, GA: AmericanCancer Society, 2012).17 Buck Institute for Research on Aging. Buck Institute Helps Launch National “HealthspanCampaign.”18 Heidenreich, Paul A., et al., “Forecasting the Future of Cardiovascular Disease in the UnitedStates.” Circulation. E-pub January 24, 2011.20 Lloyd-Jones, Donald, et al., “Heart Disease and Stroke Statistics—2010 Update: A Reportfrom the American Heart Association.” Circulation 121 (2010): e46–e215.23 Centers for Disease Control and Prevention. National Diabetes Fact Sheet: National Estimatesand General Information on Diabetes and Prediabetes in the United States, 2011. (Atlanta,GA: U.S. Department of Health and Human Services, Centers for Disease Control, 2011).25, 26 World Health Organization. Vision 2020: The Right to Sight. Global Initiative for theElimination of Avoidable Blindness, Action Plan 2006–2011. (Geneva, Switzerland. World HealthOrganization, 2007).27 McColl, Gawain, et al., “Pharmacogenetic Analysis of Lithium-induced Delayed Aging in CaenorhabditisElegans.” Journal of Biological Chemistry 283 (2008): 350–357.28 Harrison, David, et al., “Rapamycin Fed Late in Life Extends Lifespan in Genetically HeterogeneousMice.” Nature 460 (2009): 392–395.Buck Institute 2012 Annual Report 7

Letter from thePresidentAstunning percentage of the world’s populationwill be over the age of 60 by 2025. By2050, the percentage will be 41.5% in Japan,33.9% in China, and 26.6% in the UnitedStates. No surprise, then, that there is a growing globalhealth crisis as a result of these rapidly aging populations,the chronic diseases associated with aging, theinadequate support services in nearly every country,and the lack of agreement about how aging and diseaseare linked.The Centers for Medicare and Medicaid Servicesexpect national health expenditures to reach $54.2billion by 2020 for Americans age 65 years and older.A study from the Milken Institute determined thatchronic diseases will cost Americans $4.2 trillion intreatment costs and lost economic output by 2023. Butunless there are changes in what we know about agingand how we treat the aging and increasingly sick populationsamong us, that money will be spent inefficientlyon treating individual diseases or building new hospitalsrather than on disease prevention and researchingthe mechanisms of aging that are the cause of so manyage-related disorders.The Buck Institute for Research on Aging is creatingnew global alliances that advance innovation, accelerateresearch, bring new treatments to market, increaseunderstanding and education, and most importantly,extend the healthy years of life—our healthspan. Thesegoals are urgent and universally important. The effectof even a 5-year extension of healthspan will rippledramatically throughout global health care networks,economies, political systems, and societies.The Buck has never been in a better position to effectchange in the way people around the world confrontthe challenges of aging and chronic disease. And nowwe are an even stronger voice advocating preventionand personal choice as it relates to individual health.Through numerous new global initiatives and collaborations,the Buck is more visible than ever before.Playing on the global stage for the first time, theBuck is pursuing major opportunities to advancethe science and understanding of aging. Now morethan ever, we need your financial support to keep thismomentum going.As we have demonstrated during the past year and,indeed, the past decade, the Buck Institute is takinga unique approach to the problems of aging and agerelateddisease by cultivating collaborative thinkingand experimentation. We’re attracting and retainingthe best scientists with an organizational structure thatplaces research before all else, eliminating bureaucracyand the need for scientists to teach. Our state-of-theartresearch facility is expanding to accommodatea critical mass of leaders and innovative thinkers inevery field of aging research—all working together toaddress the problems of aging. This environment andapproach are fostering critical links between research,translational medicine, and health care policy. Andwe’re growing a global network that informs our perspectiveand the urgency with which we work.We are moved to action by the scale of the problemsfacing us, and we are firmly committed to this directionin the years ahead. Please join us by supporting ourmany initiatives, research, and programs.Brian K. Kennedy, PhDPresident and Chief Executive Officer8 Buck Institute 2012 Annual Report

Going Global“If I had not had breast cancer, I would never have had theidea to start 4AWOMAN to fight cancer in Madagascar. It wasa chance to do something that would relieve pain and servethe women of this country that I love—women who deservethe same level of respect and dignity that I received.”—Cinzia AkbaralyPresident, Akbaraly FoundationPartnering with Madagascar’s Akbaraly FoundationIn 2011 Cinzia Akbaraly,founder and president ofMadagascar’s AkbaralyFoundation, invited ChrisBenz, MD, to present an overviewof the global status of breast cancerat a TEDx Antananarivo eventshe had organized. Her goal wasto call attention to the plight ofMadagascar’s women, who weredying of breast and cervical cancersat a high rate.Having been successfully treatedfor breast cancer in her nativeItaly, Akbaraly was passionateto do something about the diresituation of cancer patients in heradopted country, particularly thatof the women, the social and economicheart of this island nation.“Madagascar is losing ground veryfast,” says Dr. Benz, a practicingoncologist as well as a leadingexpert on the genetic and structuralvariations among different breastcancers. “Even though Madagascarhas one of the lowest worldwideincidence rates, it has a very highdeath rate from breast cancer. Andcervical cancer, which we’re essentiallyeradicating in the UnitedStates, is the number-one cancerkiller. In Sub-Saharan Africa, bythe time a woman gets diagnosedwith breast or cervical cancer, 70%of the time it’s in an incurable stage,so she’s essentially going to die.”The Akbaraly Foundation’s4AWOMAN project targets thesetwo killers and is working to raiseawareness, expand screening, andestablish basic infrastructure inMadagascar. “These are first steps,but we really want to partner withthem and form a research alliance,”says Dr. Benz.Apart from the humanitarianreason, there’s a strong scientificreason for collaborating: the needfor data on the special type ofbreast cancer afflicting the womenof Madagascar. One of the mostaggressive forms of breast cancer iscommonly found in African-Americanwomen. It lacks biomarkersthat allow for the use of targetedchemical and hormonal therapies,and the pathways driving it areunknown. “Fewer than two dozenindigenous African breast cancershave actually been analyzed indepth,” says Dr. Benz. “We suspectthat breast cancers in Madagascarare going to represent an even moreaggressive subset of African-Americanbreast cancers, but nobody hasany data yet.”Cinzia Akbaraly became a foundingmember of the Buck AdvisoryCouncil, and that’s how she metDr. Benz. In 2012 she receivedthe BAC’s Humanitarian Award.The problem she is tackling ishuge—late diagnoses, lack of drugsand access to clinics, few treatmentoptions, no tumor registries, culturalstigmas, and economic andpolitical instability—and the needsare great. “It’s probably going totake longer than my lifetime, butCinzia’s an impatient person,” saysDr. Benz. “If this can be done at all,it will be done by Cinzia.”14 Buck Institute 2012 Annual Report

Below: Cinzia Akbaraly and Buckfaculty Dr. Chris Benz. Akbaralyreceived the Humanitarian Awardat the 2012 meeting of the BuckAdvisory Council.Board ProfileShahab FatheazamAs a managing director of Lincoln Internationaland head of the firm’s Healthcare group, ShahabFatheazam spends 60% of his time on globaltransactions. That gives this Buck Institute Boardmember a unique vantagepoint for appreciatingthe role the Instituteis poised to playin a world increasinglyimpacted by agingdemographics. “TheBuck Institute is at theabsolute center of agrowing debate thatis happening in government,pharmaceuticals, academia, and banking,”he says. “The possibilities are wide open and veryexciting. I couldn’t say no when asked to be on theBoard last year.”Fatheazam was educated at Cambridge Universityin England and earned his MBA at ColumbiaUniversity. He began his career in the internationalinvestment banking department of Kidder, Peabody& Company, where as a “newly minted” vice president,he witnessed the IPO of biotech pioneerAmgen. He got hooked on health care. “I saw allthe tools and services that were needed to makea health care company a success—it really fascinatedme.”“For women, aging is the singlegreatest risk factor for developingbreast cancer. By understandingthe different molecular and geneticsubtypes of breast cancer, newprevention strategies can bedesigned that will eliminate thisdeadly disease.”—Christopher Benz, MDProfessor and Program DirectorFatheazam, who makes his home in Chicago, iseager to bring that same fascination and a wealthof experience to the Buck Institute. “The Buck isdoing high-caliber science with exemplary facultyand staff,” he says. “I look forward to being part ofits future.”Buck Institute 2012 Annual Report 15

Year in Reviewthe time has come for realizing thepromise of regenerative medicineNew Era inStem Cell ResearchIn April 2012, the Buck Institute celebrated theopening of its Regenerative Medicine ResearchCenter, bolstering its unique efforts to exploitthe promise of stem cell technology to advanceaging research. The goal is to move more rapidly indeveloping new therapies to prevent and treat thediseases of aging.The new research center is a California Institute forRegenerative Medicine (CIRM) Center of Excellence—one of just 12 stem cell facilities approved for fundingthroughout the state. The citizens of California,through CIRM, are making this urgently neededresearch possible. In nine laboratories of this state-ofthe-artbuilding, stellar scientists, including two newfaculty, are currently collaborating on research andusing stem cell technology to detect, delay, prevent,and treat the scourges of aging—Alzheimer’s andParkinson’s diseases, cancer, cardiovascular disease,macular degeneration, and stroke.The new building, which incorporates many “green”technologies, symbolizes for the Buck the hope andpromise of stem cell research. This fitting stage for theBuck’s expanded focus on regenerative medicine wouldnot have been possible without CIRM, which providedhalf of the funding for the $41 million building. CIRMis also funding some of the stem cell research underwayin the Center’s research labs and supporting the crucialtraining of new stem cell scientists. These investmentswill benefit Californians and people around the worldfor years to come.16 Buck Institute 2012 Annual Report

“We are so proud to have had the opportunityand privilege to fund part of the constructionof this new building. We are looking forward tohearing about all of the wonderful research thatwill come out of this facility.”—Jonathan Thomas, ChairCIRM Independent Citizens’ Oversight CommitteeLeft to right: Jonathan Thomas, Chair,CIRM; Brian Kennedy, PhD, BuckInstitute President and CEO; AlanTrounson, PhD, President, CIRM; JamesEdgar, Chair, Buck Board of Trustees.Above: Model of completed Buckcampus. Future funding will enableconstruction of two additionalresearch buildings approved in theBuck master plan.Buck Institute 2012 Annual Report 17

Year in Review: new FacultyBoosting the Regenerative Power ofAdult Stem Cells to Enhance LongevityThe Buck’s newest faculty member, HenriJasper, PhD, brings an international reputationas a stem cell biology star to the Institute.Jasper is renowned for making fundamentaldiscoveries about the role of stress signaling and agingon stem cell behavior.The German-born scientist spent the summer of 2012relocating his lab—1,500 genetically unique strains offruit flies (approximately 20,000 individual flies) andsix lab members—from the University of Rochester tothe Institute’s Regenerative Medicine Research Center.Jasper, who received his PhD from the University ofHeidelberg in Germany and the European MolecularBiology Laboratory, is focused on enhancing the functionof adult stem cells. As we age, adult stem cells—which live in pockets throughout our bodies and go towork when important tissues are damaged—becomeless effective. He wants to understand how adult stemcells regenerate damaged tissue and why their regenerativepotential declines with age.to study the underlying mechanisms causing retinaldiseases such as macular degeneration, a major causeof blindness and visual impairment in older adults. TheJasper Lab will collaborate with the Lamba Lab, whichis developing stem cell replacement therapies to treatmacular degeneration.The Buck Institute was on Jasper’s radar screen as apotential place to work for many years. A visit in 2011finally convinced him to make the move. “I was struckby the collaborative spirit at the Buck—it really is aunique environment,” says Jasper. “The opportunity todo interdisciplinary work with so many outstandingscientists focused on aging and disease is very exciting.”Jasper was one of the first aging researchers to usestem cells in the intestines of fruit flies to test howaging affects stem cell function. Jasper is also usingthe retinas of fruit flies to determine how insulin andstress-signaling pathways control tissue regeneration,metabolic homeostasis, and cell death.“We think the short-lived fruit fly, with tissues andgenetics that can be easily manipulated, offers a perfectscientific palette for this inquiry,” Jasper says. Whilethe fruit fly is an ideal model system for his work, heplans to expand his research to mammals, specificallyto the respiratory systems of mice, which regeneratefrom a stem cell population that closely resembles theintestinal stem cells of fruit flies.Jasper has already begun collaborating with the Kennedyand Kapahi labs. The three groups intersect intheir interest in the effects of diet and stress on aging,and they plan to explore the effects of metabolic signalingon stem cell maintenance and regeneration.Jasper recently received a highly competitive grant of$1 million from the National Eye Institute to continueresearch on developing the fruit fly as a model to studydegenerative eye diseases. He is focusing on the retina,the light-sensitive tissue lining the inner surface ofthe eye. His aim is to understand the complex cellularprocesses that kick in when the retina needs to eliminatecellular debris, including the wreckage associatedwith aging. The funding will enable the Jasper Lab18 Buck Institute 2012 Annual Report

“It’s the science that counts, and that’s whyI’ve come to the Buck. The Institute is poisedto make major contributions to the field ofregenerative medicine, and I am very excitedto be a part of that.”—Henri Jasper, PhDProfessorBuck Institute 2012 Annual Report 19

Year in Review: new FacultyInnovating with Stem Cells to Treat Vision DisordersFor people suffering from age-related maculardegeneration—a disease that progressivelydestroys central vision—Deepak Lamba, MBBS,PhD, is offering new hope with his stem cellresearch, which is under way in the Buck’s new RegenerativeMedicine Research Center.Vision problems often spark a downward spiral in thehealth of older people. An estimated 11 million peoplein the United States alone have some form of maculardegeneration, making it the leading cause of vision lossin Americans 60 years of age and older. Dr. Lamba, whojoined the Buck Institute in October 2011, is using stemcell technology to identify new methods to combatmacular degeneration as well as glaucoma and retinitispigmentosa.Photoreceptors, Dr. Lamba says, are the key cellsneeded to treat macular degeneration. As a graduatestudent, he pioneered the development of efficientmethods of making these retinal cells from humanembryonic stem cells (hESCs). Taking advantage ofnew technology, he also derives retinal cells frominduced pluripotent stem cells (iPSCs). An iPSC is acell taken from any tissue that has been reverse-engineeredto behave like an embryonic stem cell. Utilizingboth hESCs and iPSCs, he has generated differentiatedphotoreceptors—the cells in the eye that respond tolight—and has successfully transplanted these cells intothe eyes of mice. When Dr. Lamba tested the stem-celltransplantedeyes for vision, they responded to light.“Now I need to determine if there will be any issueswith tumor development in the new cells,” says Dr.Lamba. “I also need to ascertain how long the transplantedcells survive.”Dr. Lamba’s work goes beyond developing stem cellreplacement therapies. He is using iPSC technology togenerate eye cells from skin cells to better understandand prevent, or develop treatments for, diseases likeglaucoma. Eye diseases in the glaucoma group oftenshare traits such as high eye pressure, damage to theoptic nerve, and gradual sight loss. “Glaucoma is acomplicated disorder since it affects the ganglioncells, which project from the eye to the brain,” saysDr. Lamba. “Transplantation would be much moredifficult, so I’m using iPS cell technology to create cellsthat can be used to screen existing drugs in order toidentify those that might be useful as a treatment.”Dr. Lamba came to the Buck because he wanted to bepart of the Institute’s larger focus on delaying the agingprocess itself. He is studying retinitis pigmentosa, agroup of hereditary eye diseases that lead to blindness.“In many people, the symptoms of the disease don’tshow up until age 50 or 60. Delaying the aging processwould make a huge difference for these patients.”20 Buck Institute 2012 Annual Report

“Impaired eyesight often heralds a sharpdecline in quality of life for seniors. Losingthe ability to read, drive, and safely navigateone’s surroundings can be devastating.”—Deepak Lamba, MBBS, PhDAssistant Professrabove: Lamba Lab members are(clockwise from left): Mark Gutierrez,Deepak Lamba, Joe Reynolds, Ilan Riess,and Thelma Garcia.Buck Institute 2012 Annual Report 21

Year in Review: New discoveryReversing the Aging ProcessBelow: VictoriaLunyak, PhD,AssociateProfessor.What is going wrong with our biologicalclock as we age? Victoria Lunyak, PhD,and her lab team began searching foranswers by hypothesizing that DNAdamage in the genome of adult stem cells would lookquite different from the age-related damage occurringin regular body cells.Human adult stem cells regenerate their tissues of origin,always keeping the body in a state of flux. For example,muscle tissue is fully regenerated every 15 years, skincells become “new” every 4 weeks, and the cells in ourskeleton turn over every 10 years. Adult stem cellsalso kick into action when tissues are damaged and inneed of repair. Unfortunately adult stem cells lose theirregenerative powers with age. When this happens, thebody no longer replaces the damaged tissue as well as itonce could, which leads to a host of diseases.Much of the damage caused by aging is thought to bea result of cells losing telomeres, the caps found at theends of chromosomes. But since adult stem cells areknown to keep their telomeres, Lunyak suspected thatdifferent mechanisms were at play that would explainaging in adult stem cells.In a landmark study undertaken with scientists fromthe Georgia Institute of Technology, University of California,San Diego (UCSD), Howard Hughes MedicalInstitute, Memorial Sloan-Kettering Cancer Center,International Computer Science Institute, Applied Biosystems,and Tel Aviv University, Lunyak’s team at theBuck Institute showed that they can reverse the agingprocess in human adult stem cells. They accomplishedthis by suppressing the accumulation of toxic transcriptsfrom retrotransposons, the genetic elementsthat make up about 42% of the human genome.“By rewinding the cellular clock in this way,” explainsLunyak, “we were not only able to rejuvenate ‘aged’human stem cells, but to our surprise we were ableto reset them to an earlier developmental stage byup-regulating the pluripotency factors—the proteinsthat are critically involved in the self-renewal of undifferentiatedembryonic stem cells.”The study’s findings were published in the September1, 2011, issue of Cell Cycle. If Lunyak’s team can nowfind a way to keep adult stem cells young, the cellscould be used to repair damaged heart tissue after aheart attack, heal wounds, correct metabolic syndromes,produce insulin for patients with type 1 diabetes, curearthritis and osteoporosis, and regenerate bones.In its most recent discovery, the Lunyak Lab has foundthat noncoding RNAs (ribonucleic acids), which makeup a large portion of the human genome, providevital scaffolding for cellular processes in adult stemcells. This findingimplies that thechronic diseases ofaging arise fromthe deteriorationof this scaffoldingrather than fromgenetic mutations,giving researchersadditional targetsfor therapeuticinterventions.22 Buck Institute 2012 Annual Report

Year in Review: educationTraining a New Generation of ScientistsMore than a decade ago, Richard Klausner,former Chairman of the National Committeeon Science Education, said, “Allof us have a stake, as individuals and as asociety, in scientific literacy.” Since then, the need forscience education has become critical, especially as therole of the United States as a global leader in technologyis called into question. In the San Francisco BayArea, the challenging economic climate facing publiceducational institutions has made the situation evenmore difficult. Some schools havebeen forced to reduce or eliminatecourses, extracurricular activities,and teacher training in the sciences.Providing assistance in this crucialarea was at the core of the BuckInstitute’s educational outreach in2011–2012.The Buck’s mission is to extendhealthspan—the healthy, productiveyears of life—through researchand education. In 2011–2012 theBuck Institute responded to regionalneeds by expanding its educationalprogramming, which in the previous 3 years hadreached 3,000 children. Following the directives of thePresidential Science, Technology, Engineering andMath campaign (STEM), the Buck tailored its educationalprogramming to enhance the participation andperformance of the region’s youth in science and math.celebration of science that drew 4,000 people to itsNorth Bay Discovery Day main event. The Institute alsobroke ground on a new, state-of-the-art, 1,500-squarefootdemonstration laboratory and classroom, whichwill dramatically enhance its ability to provide uniquetraining in science for children and adults.Throughout 2011–2012, the Buck offered free communityeducation seminars for adults. Buck scientists andexecutive staff visited community and professionalgroups to speak about the Institute’s research advancesand discoveries in aging and age-related diseases. TheInstitute hosted a program called Science in the City—aseries of intimate lunches held at the Olympic Club inSan Francisco that introduced Buck scientists and theirresearch to members of the business community.All of these initiatives reflect the Buck Institute’s dedicationto developing the next generation of scientists.They also underscore the Buck’s commitment to serveas a regional leader in educating young scientists andthe general public, and to sharing the results of ourresearch as broadly as possible—research that offershope for a healthier lifespan for aging populationseverywhere.The Buck hired its first full-time education coordinatorfor K–12 as well as a director of postdoctoral education.The Institute took the lead in coordinating localactivities for the Bay Area Science Festival, a weeklongPathways to priming the education pipelineAttractInvite children tolearnRetainChoose to keeplearningPersistLead studentsto graduateAttachContinue toSTEM careersThe Buck’sEducationProgramAlgebra AcademyBay Area ScienceFestivalHigh School SummerScholarsUndergraduateInterns: 2- and 4-yearGraduate Students:MS and PhDPostdoc TraineesPrimary toHigh SchoolUndergraduateEducationGraduateEducationProfessorate/IndustryBuck Institute 2012 Annual Report 23

Year in ReviewAccomplishmentsJuly 2011The ProvidenceJournal runs an op-edco-authored byBuck faculty JulieAndersen, “Are WeGiving U.S. InfantsToo Much Iron?”Proteome Sciencesand the Benz Lab todevelop biomarkertests to improvebreast cancer treatment.August 2011Buck CEO BrianKennedy is quotedin The New YorkTimes: “Longer livesfor obese mice withhope for humans ofall sizes.” The articlefocuses on a studyinvolving the experimentaldrug SRT-1720.On August 9, 2011,the Buck Institute wasawarded a patenttitled “Small Moleculesthat Replaceor Agonize p53Function” (US Patent# US7,994,184 B2).P53 has been shownto have the ability topromote or retardaging, depending onthe context of its regulationand activity.The inventor is DaleE. Bredesen, MD.September 2011Buck Institute andBiotica collaborationwill evaluate rapamycinanalogs andother polyketidesin a broad range ofage-related diseasemodels to identifynovel therapeutics.Lunyak study in CellCycle, “ScientistsTurn Back Clockon Adult Stem CellAging.”Buck Board addsfour new members:Ned Powell, ShahabFatheazam, BarbaraMorrison, and LarryRosenberger.Buck CEO BrianKennedy is quotedextensively in TheScientist regardingthe controversies overthe role of sirtuins inlifespan extensionand age research.October 2011The appointment ofJoseph Antoun, MD,as Adjunct Facultymarks the Buck Institute’sfirst foray intopublic policy.New faculty DeepakLamba, MBBS, PhD,arrives at the BuckInstitute. Maculardegeneration isadded to the roster ofage-related diseasesstudied at the Buck.Buck CEO BrianKennedy visits theMiddle East where heexplores partnershipswith pharmaceuticalcompanies, governments,and researchinstitutes.The Arab Times andKuwait Times publishop-eds by Buck CEOBrian Kennedy on theepidemic of type 2diabetes now impactingthe Middle East.November 2011Buck Institute coordinatesNorth BayDiscovery Day atInfineon Raceway onNovember 5. Morethan 4,000 peopleattend the signatureevent during the BayArea Science Festival.Buck faculty JudithCampisi is quoted ina New York Timesarticle focusing onsenescent cells andaging.December 2011The Kleiman MultimediaStudio opens atthe Buck Institute.Buck faculty JudithCampisi and SimonMelov are quoted ina National Journalarticle, “Longevity: AManual.”James Edgar electedas Chair of the BuckBoard of Trustees.January 2012The San FranciscoABC affiliate runs astory on the Buck’sgeothermal project.Buck CEO BrianKennedy goes toTokyo and Singaporeto forge connectionsbetween the Instituteand biotech andpharmaceutical companies.February 2012Research from theMelov Lab: A study inScience TranslationalMedicine shows massagereduces inflammationand promotesgrowth of new mitochondriafollowingstrenuous exercise.The story gets pickedup by several nationalmedia—NPR,Bloomberg, and USAToday.Buck CEO BrianKennedy goes toCentral America toset stage for scientificcollaborations thatwould bring postdocfellows to Buck Institutelabs.The Costa Rica Newspublishes an op-edby Brian K. Kennedy,“A Wake-Up Call forCosta Rica.”March 2012Buck Institute holdsScientific Symposium:Stem Cells andAging.Ambassador FayHartog Levin and LewReid join the Board ofTrustees.Buck Instituteappears on CapitolHill; Buck CEO BrianKennedy helps launchnational “healthspan”campaign.April 2012Henri Jasper, PhD,hired as new facultymember. Arrives inthe summer fromRochester, NY, andcontinues researchaimed at promotinglongevity by enhancingthe activity ofadult stem cells.USA Today runs astory about the 100thbirthday of BuckCEO Brian Kennedy’sgrandmother inLouisville, KY. Thepiece features aninterview with Kennedyabout aging research.The Buck Institute’snew RegenerativeMedicine ResearchCenter opens on April14; the Institute’sfirst public openhouse draws 1,000attendees.May 2012The Greenberg Labpublishes a studyin The Proceedings ofthe National Aca demyof Sciences focusingon modifying scartissue followingchronic stroke.The Buck AdvisoryCouncil meets andbestows awards forscientific and humanitarianachievement.June 2012The Glenn Foundationawards $1 million toestablish trainingfellowships in agingresearch.Steve Burrill and JimGerber join the BuckBoard of Trustees.The Ellerby Lab publishesa study in CellStem Cell—scientistscorrect genetic mutationresponsible forHuntington’s diseasein human inducedpluripotent stemcells.24 Buck Institute 2012 Annual Report

Buck Institute Publications by Year103Total 1,100201287982009201010282103201175Board ProfileCatherine H. MunsonMotivation comes in all forms. Most people knowCatherine Munson as a Bay Area real estate professionalassociated with the modern residentialhousing developerJoseph Eichler. Butan opportunity toreturn to her scientificroots prompted theover-scheduled communityactivist to jointhe Board of Trusteesof the Buck Institutein 2004. Munson graduatedwith an MA inmicrobiology and biochemistry from the Universityof Nebraska in 1950. She worked in basic researchbefore beginning her career in real estate. “I knewthe Buck was involved in revolutionary medicalresearch, and I wanted to be a part of it,” shesays. “As I got to know the faculty members, I justcaught fire.”200694200785200879Munson, who is the very active CEO of Lucas ValleyProperties, served as Board Chair in 2010–2011.“Supporting the Buck Institute is now my numberonepassion and commitment,” she says. “The Instituteis the most significant organization in MarinCounty. Everyone ages—the Buck has a humanitarianmission that is impacting global health.”20031041200463200578Increasing the Institute’s visibility is always on herradar screen. “Those of us who live in the Bay Areaare incredibly blessed to have access to theseworld-class scientists who are working to find realsolutions to the demographic challenges that faceour society,” says Munson. “I am extremely proudand fiercely enthusiastic to spread the word abouttheir efforts.”1999200020012002Buck Institute 2012 Annual Report 25

Postdoc COLLaborationsthe time has come for bold science,creative collaboration, and new therapiesPostdoc Collaborations—Heart and Soulof Science at the BuckAt the Buck Institute, there are few walls, littlebureaucracy, no turf wars. It’s an environmentdesigned to encourage collaboration acrossdisciplines—one where eager young scientistscan bounce ideas off each other and try novelapproaches to solving some of the fundamental problemsin aging science.In most research organizations it’s the young scientists—the postdoctoral fellows who have completed theirPhDs—who do the yeoman’s work in the laboratories.The Buck Institute is no exception. But at the Buck,postdocs have a unique advantage. They are not onlymentored by outstanding faculty members, but theyalso have daily opportunities to reach beyond their labsto form synergistic partnerships—collaborations bothwithin and beyond the Buck that will advance knowledgeand understanding of the biological processes ofaging. Their dedication and discoveries may eventuallylead to new therapies for some of aging’s worst maladies—cancer,heart disease, and Parkinson’s.This section highlights postdoc research collaborationsat the Buck. Featured are stories of six young scientistswho work in the Andersen, Kapahi, Kennedy, Melov,and Campisi labs. Their laser focus and “big picture”attitude exemplify what drives science and researchhere at the Buck.While these six postdocs have expertise in differentdisciplines and technologies, all are working on projectsinvolving rapamycin—a drug already tested andapproved by the FDA for suppressing the immunesystem of transplant patients. In 2009, a trio of labsreported that rapamycin—a compound discovered onEaster Island in 1964—extended the lifespan of miceby 12%. Rapamycin’s remarkable ability to delay theaging process in mice and other species, along with itsFDA-approved status, makes the drug a source of hopeand great excitement in aging research.26 Buck Institute 2012 Annual Report

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Postdoc COLLaborations28 Buck Institute 2012 Annual Report

Collaborating on a Parkinson’s DiscoveryIn the Andersen Lab, Almas Siddiqui has beenworking on Parkinson’s disease research since2008. She’s trying to determine what oxidativestress does to the neural cells of patients with thedisease. Oxidative stress, which produces free radicalsand is a normal byproduct of cellular metabolism,increases with age. “And increased production of freeradicals can create a state of imbalance,” says Siddiqui,“that may contribute to the cell death associated withParkinson’s disease.”Three years ago when she first began working withrapamycin, an immune-suppressing drug currentlyapproved for use following organ transplants, Siddiquifound that there was an improvement in the functionsof the mitochondria, the powerhouses of the cells,when she applied rapamycin to a cell culture model ofParkinson’s disease. But what really surprised her wasthe drug’s effect on parkin, a protective protein whoseloss of function is reported in Parkinson’s patients.“We never expected that, when we gave rapamycin tocells in a dish, we would see an increase in the parkinprotein levels because generally rapamycin decreasesproduction of new protein,” says Siddiqui. Why wasrapamycin having this positive effect on parkin? Toconfirm her suspicion that the increase was happeningat a different level of gene expression than she hadexpected, Siddiqui turned to Aric Rogers, a postdoctoralfellow in the Kapahi Lab, which has an overallfocus on aging and nutrition.Rogers is an expert in the biology of mRNA translation—especiallyas it relates to aging. Translation isthe final step of gene expression, when our geneticcode prompts the production of proteins. It occursafter individual genes encoded in the DNA have beentranscribed into RNA, an intermediate that may ormay not be translated into functional proteins. Siddiquiknew that the transcripts of the gene encoding parkinhad not increased, which suggested that the increasedlevels of the protein might be due to an increase intranslation. This could be the case if there were increasedassociation of parkin transcripts with the machinerythat synthesizes new proteins. To address this possibility,Siddiqui sought Rogers’s technical expertise.Finding the answer was important because, as Rogersexplains, “Rapamycin, the drug used in Almas’s experiment,targets a protein complex called TOR. This complexcontrols a number of cellular processes, includingthe synthesis of new protein. The technique that Iadapted from translation state array analysis can beused to determine changes in the synthesis of specificproteins like parkin.”Siddiqui’s finding is important, Rogers says, because “ifyou can understand where the desired effects of a drugare coming from, you can develop a new drug or combinationsof drugs that avoid unwanted side effects.Rapamycin targets TOR, which in turn modulatesprotein synthesis, but TOR also controls a number ofother cellular processes. Drugs can be used to targetjust those factors affecting protein production, or otherdrugs may be added to lessen undesired side effects.”Their collaborative work on understanding rapamycin’simpact on the protein produced in the cell culturemodel of Parkinson’s disease points to a potential useof the drug—or analogs of it called rapalogs—as atherapeutic for Parkinson’s disease and other neurodegenerativedisorders. “There’s a huge emphasis nowon drugs that target translation,” says Rogers, “andbecause rapamycin is already approved by the FDA, itwill be much easier to get these rapalogs to clinical trials.”“Parkinson’s is still a big black box,” adds Siddiqui,who is moving her research into mice, “but the futureis now much more promising.”above:The centraldogma ofmolecularbiology.left: In a conversation-fostering space, postdocsAlmas Siddiqui and Aric Rogers discuss their jointresearch project.Buck Institute 2012 Annual Report 29

Postdoc COLLaborationsExploring Rapamycin’s Effect on Heart and Bone HealthPostdoctoral fellows Monique O’Leary andJames Flynn are engaged in a collaborationbetween the Kennedy and Melov labs thataims to evaluate the health benefits of treatingmice with the drug rapamycin. Some of the KennedyLab’s many projects focus on cardiovascular healthand the mTOR pathway—the pathway that rapamycininhibits and that modulates aging across many differentorganisms. The Melov Lab is providing genomicexpertise and technology to this project, and to theentire Institute.Four years ago Brian Kennedy hired O’Leary as apostdoc in his laboratory at the University of Washingtonto study genes involved in aging and age-relateddiseases in mice. In 2010 Kennedy, now the Buck Institute’spresident and CEO, asked O’Leary to relocate hislab from the University of Washington and to manageit on a day-to-day basis in addition to working on herown research projects. “I study the process of translation,when proteins are being made within a cell,” saysO’Leary. “The TOR signaling pathway plays a crucialrole in translation and the aging process.” Flynn is anexpert in gene expression, and both scientists workwith mice to understand how they age and to explorepotential therapeutics for age-related diseases.Determining a potential use for rapamycin to treatage-related disorders such as osteoporosis and heartdisease is a large part of their work at the Buck. In thisstudy, the two postdocs wanted to see what happenson a genomic level to a normal mouse as it ages—whatgenes are turned on, what genes are turned off, andwhy the expression of these genes changes over time.“We want to look at the signaling molecules downstreamof the actual molecule that’s called mTOR andto understand how the mTOR signaling pathway relaysAbove: Using microCT imaging and 3D analysis software, it is possibleto “digitally” slice through bones revealing their inner structure.Shown here are the middle sections of mouse femurs from youngmice (left) compared to older mice (center and right, respectively).This imaging can reveal the effectiveness of a drug in maintainingbone mass. 3D model by Michael Presley.its signal throughout a cell or within an organism,” saysO’Leary. “From previous studies, we knew that rapamycinextended lifespan, but nobody had done anystudies to see if it extends healthspan.”To add a unique approach to their rapamycin study,Flynn was sent to Belgium for extensive training inmicro CT imaging—a technique that enables himto get 3D images inside the femurs of mice. The liveimaging allowed Flynn and O’Leary to observe themice and evaluate their health as they aged. So far,the postdocs have followed a group of middle-aged(12 months of age) mice for a year, examining variousfunctions in them and analyzing bone structure, heartfunction, and muscle mass every 3 months. They havealso put a group of “old-aged” mice (24 months ofage) on a diet that includes rapamycin and conducteda similar examination of cardiovascular health, bonedensity, and muscle mass.Based on their experiments, O’Leary and Flynn haveco-authored a paper and submitted it for publication.“The initial results have been extremely encouraging,especially because these older animals are consideredsenior citizens in their mouse population,” says Flynn.“We think we’ve identified a large number of genes thatare turned on or off in the mice as a result of havinghad rapamycin added to their diet. We’re also lookingat inflammation as one of the factors that is impactedby rapamycin.”Flynn learned the technique he used to measureinflammation from a postdoc in the Campisi Lab,Remi-Martin Laberge, whose desk is just a shoutingdistance away from his own. “The ability to go and talkto someone who’s an expert in this aspect of aging isunique at the Buck because there are few places wherethere are so many diverse experts on the biology ofaging,” says Flynn. “It’s really great to be able to go tosomeone like Remi and get feedback on a part of yourproject. You can’t be an expert in everything, so beingable to collaborate with experts helps move the scienceforward and accelerate the research.”Initially skeptical that their time-consuming projectwould have any unique beneficial results, O’Learyis looking forward to getting their paper published.“Many labs around the country are studying rapamycin,with an eye toward its potential use in humans.We are hoping that our paper makes a significantcontribution to that body of work.”30 Buck Institute 2012 Annual Report

Below: Postdocs Monique O’Leary andJames Flynn review data from mousestudies involving the drug rapamycin.Buck Institute 2012 Annual Report 31

Postdoc COLLaborationsReducing the InflammationThat Can Contribute to CancerRemi-Martin Laberge and Su Liu, postdoctoral fellowsin the Campisi and Kapahi labs, study senescence—theprocess that occurs when cells lose their ability todivide. The two scientists are now working on a jointproject between their respective labs to identify the effects ofrapamycin on senescent cells.Laberge, who earned a PhD at Canada’s McGill University oncancer drug resistance, has been with the Campisi Lab since 2008.He is immersed in studying the inflammatory processes that areassociated with senescence and their impact on the developmentof cancer. Liu, who is originally from China, joined the KapahiBelow: Su Liu and Remi-Martin Laberge lookat senescent cells that have been treated withrapamycin. The postdocs often work in one of thecell culture rooms near the Campisi Lab.32 Buck Institute 2012 Annual Report

Lab in 2010 after receiving a PhD in pathology fromthe University of Rochester where she studied prematureaging in a mouse model.Pankaj Kapahi and his lab had been studying the roleof the target of rapamycin (TOR) on flies and wormsin aging, but were considering extending their workto human cells and mice. So when Kapahi suggestedto Laberge that he test rapamycin’s effects on mice andhuman senescent cells, Laberge took up the challenge.In the Campisi Lab, Laberge began by applying rapamycinto cells that he had forced to senesce by exposingthem to ionizing radiation. Laberge saw lowerinflammation in those senescent cells. Next Labergebegan studying senescent cells that actually stimulatethe growth of cancer cells. “When cells senesce, theyspew proinflammatory cytokines, and when senescentcells accumulate, their signals lead to chronic inflammation,which drives cancer. The majority of age-relateddiseases are boosted by chronic inflammation.”When Liu joined the Kapahi Lab, she began growinghuman senescent cells in culture along with cancercells to see what would happen. She found, as predictedby earlier Campisi Lab experiments, that the senescentcells stimulated the growth of the cancer cells, whichbecame more aggressive and invasive. That’s why, Liusays, it’s important in humans to reduce the numberof senescent cells and the inflammation they cause.“The cancer might grow anyway, but it grows fasterwhen the senescent cells are around,” explains Laberge.“They’re stimulating cells that are not very invasiveto become more invasive, breaking the barriers thatprevent those cells from migrating into other tissues.”Liu and Laberge found that rapamycin could block thisstimulating effect.Laberge also found that many cytokines—those inflammatorymolecules in the blood that slowly increase aspeople age—are secreted at much lower levels in thepresence of rapamycin. The cytokines are secreted bysenescent cells and are potentially in the vicinity of cancercells. Since the level of cytokines in blood is associatedwith cardiovascular disease and neurodegeneration,he is now interested in “getting rid of senescent cells ortuning down the chronic, low-level inflammation that isspecifically induced by senescent cells.”function, which might explain the differential role ofsenescent cells in different contexts,” says Liu. “Forexample, senescent cells in the cancer context are a badthing, but in the context of wound healing they play abeneficial role. We need to find a way to target differentgroups of cytokines.”Chemotherapy drugs induce DNA damage—that’s howthey kill cancer cells, says Laberge. “Often when youtreat patients with chemotherapy drugs, they don’t justwork on the cancer cells. They also affect the surroundingnormal cells, and that will induce senescence inthose cells. This is a big problem because the cancer cellsthat aren’t killed by chemotherapy will now be fueled bythe surrounding senescent cells that were just created.”Laberge says rapamycin is so far the best tool tocome along for identifying pathways associated withhealthspan extension. But the compound can causediabetes and suppress muscle function. To uncouplethe positive and negative effects, he and Liu are tryingto dissect the molecular pathways that are impacted byrapamycin. “Hopefully we’ll find something that willbe much better than rapamycin—something that willspecifically enhance rapamycin’s beneficial effects butnot enhance its negative effects.”For Laberge and Liu, their joint project is a perfectexample of the benefits of Buck collaboration. Otherscientists at the Buck and elsewhere contributed totheir work. Working alone, it would have taken thepostdocs years to advance their research to where itis today. “Discoveries go faster here because we’re allunder the same umbrella of aging,” says Laberge. “Weall have the same goals, but we study different aspectsof aging. And as we learn more about molecular mechanismsin different organisms, we can then apply themto the various disease systems that others are researchingat the Buck.”This past year, Liu and Laberge tested over 200 differentcytokines and found that rapamycin did notinhibit all of them, just a group of them. “This isvery important because each cytokine has its distinctBuck Institute 2012 Annual Report 33

Gerosciencethe time has come for geroscience—fromconcept to reality to national participationThe Buck Institute is the birthplace of geroscience,a new discipline focused at the intersectionof normal aging and chronic disease.The term “geroscience” entered the scientificlexicon in 2007 when the Buck Institute received oneof nine Roadmap for Medical Research grants from theNational Institutes of Health.With this grant, the NIH aimed to support researchteams that are “addressing health challenges that havebeen resistant to traditional research approaches.” The$25 million award validated our mission to extendhealthspan and our collaborative interdisciplinaryresearch model. It recognized the value of the Buck’sfounding objective—to bring together top scientistswith highly disparate backgrounds who share a passionfor solving the tough, profoundly complex biomedicalproblems of aging.In 2012, the formation of a Trans-NIH GeroscienceInterest Group (GSIG) underscoredthe success of our approach. The GSIGincludes scientists from some of the27 research institutes and centers thatcompose the NIH who are keen toapply the discoveries in aging researchto their own research agendas, whichoften are focused on a particular disease.One of the GSIG’s goals is to promotethe application of aging researchby developing public/private partnershipswith scientific societies, industrygroups, and other research institutes.At the Buck, we see this growing interestin aging research as the beginningof a groundswell that will acceleratediscoveries and speed development ofnew therapies to prevent or treat thediseases of aging. And our scientistsand their laboratories are at the forefront,keeping the momentum going.Geroscience at the Buck InstituteEvery faculty member at the Buck Institute is involvedin geroscience. While their specialties range across theentire spectrum of age research—cellular bioenergetics,stress biology, epigenetics, regenerative medicine,neurodegeneration, molecular physiology, and bioinformatics—theBuck faculty share an intense focuson the connection between aging and chronic disease.Within and beyond their laboratories, the Buck facultycreate an atmosphere that supports discovery andthrives on shared knowledge. While each faculty memberruns their own laboratory and leads their own teamof scientists, all are committed to an organizationalstructure that has no departmental boundaries andlittle bureaucracy. Brilliant, entrepreneurial, collaborative,and visionary—the Buck faculty are shedding newlight on aging and developing novel solutions to someof its most daunting challenges.REGENERATIVE MEDICINEAdult Stem CellsEmbryonic Stem CellsInduced Pluripotent Stem Cells (iPSCs)AGE-RELATED DISEASEAlzheimer’sCancerCardiovascularHuntington’sMacular DegenerationMetabolic SyndromeOsteoporosisParkinson’sProgeriaStrokeAGING STUDIESDietary RestrictionDNA DamageGenetic PathwaysMitochondrial FunctionOxidative DamageSenesenceTranslationTECHNOLOGYBioinformaticsGenomicsMetabolomicsMorphology and ImagingProteomics34 Buck Institute 2012 Annual Report

Geroscience Studies at the Buck“We have recent evidence that the aging processis malleable, and it has been observed in severalanimal models that when aging is delayed, soare the diseases and disabilities that normallyaccompany aging.”—Dr. Felipe Sierra, GSIG Founder and Director of theNational Institute of Aging’s Division of Aging BiologyNIH Record, August 17, 2012Buck Institute 2012 Annual Report 35

FacultyProfiles“My greatest hope is that our workhere at the Buck will allow us totreat Parkinson’s at the earliestpossible stage, so treatment canbegin before the disease has achance to progress. That wouldfree patients to live fulfilling liveswithout major disability.’’Julie Andersen, PhDProfessorParkinson’s Disease—Julie Andersen, PhDJulie Andersen is an expert on Parkinson’sdisease—an incurable, progressive neurodegenerativedisorder that currently affectsover 1.5 million people in the United States.Pursuing research that is fundamental fordeveloping treatments for this complexdisease, which causes a progressive declinein movement and muscle control, she hasidentified early risk factors, such as elevatedlevels of iron and declining amounts of aprotective antioxidant called glutathione,and several novel drug treatments (lithium,flavonoids).The Andersen Lab examines the role of the proteinsthat are involved in nerve cell degenerationand is working to identify biomarkers forParkinson’s that could result in therapeuticinterventions in the early stages of the disease.Anderson is interested in how the aging brainaffects disease.Andersen was a postdoctoral fellow at HarvardMedical School and Massachusetts GeneralHospital. Prior to joining the Buck Institutein 2000, she was an associate professor at theAndrus Gerontology Center at the Universityof Southern California.Christopher Benz, MDProfessor and Program DirectorBreast CancerChristopher Benz, MD, joined the Buck Institutein 2000 as a founding faculty member. Asenior member of the UCSF Cancer Center’sBreast Oncology Program, he set up the university’sfirst laboratory for the study of humanbreast cancers. Dr. Benz not only continues totreat breast cancer patients at UCSF’s CarolFranc Buck Breast Care Center, but he alsois the co-principal investigator of the BuckInstitute–UC Santa Cruz Genome Data AnalysisCenter—one of seven national centers inThe Cancer Genome Atlas program.The Benz Lab was among the first to studywhy age is such an important determinant forthe onset and development of breast cancer,why the incidence of breast cancer increaseswith age, and how the aging process altersbreast cancer biology. In a search for personalizedtreatments for each patient’s breast cancersubtype, Dr. Benz and his team also explorethe genetic and structural differences amongbreast cancer types, as well as new therapeuticstrategies.Dr. Benz helped organize the Marin Women’sStudy (MWS). Launched in 2006, the MWSwanted to detect environmental factors, lifestylepatterns, and individual biofactors contri butingto breast cancer risk in Marin County, whereincidence rates of the ER-positive type ofbreast cancer are among the highest in theworld. By alerting women to the hazards oftaking combination hormonal therapy atmeno pause, the MWS was able to documenta sharp decline in hormone use and a resulting33% reduction in new breast cancer cases inthe county.36 Buck Institute 2012 Annual Report

Faculty ProfilesMartin Brand, PhDProfessorEnergy Metabolism of CellsMartin Brand is an authority on mitochondria—theenergy-converting unit of cells—and their influence on aging and disease.After receiving his PhD in biochemistry atthe University of Bristol in England, he was apostdoctoral fellow at Johns Hopkins Universityin Baltimore, Maryland; a faculty memberat the University of Cambridge; and then agroup leader at the Medical Research Council.At Cambridge, he began collaborative studieswith Buck faculty. He joined the Buck Institutein 2008.The Brand Lab is studying mitochondria,which extract energy from nutrients anddistribute it to drive the machinery of life in aprocess that also releases free radicals. Believedto be one of the primary actors in the agingprocess, free radicals are implicated in numerousage-related diseases, including cancer,heart disease, stroke, and many neurologicaldisorders.Brand’s lab envisions treatments that wouldminimize the release of free radicals withoutinhibiting mitochondrial energy metabolism.His lab is collaborating with other Buck labs toevaluate the role of the mitochondria in agingand in age-related diseases such as cancer,diabetes, Parkinson’s, Alzheimer’s, and Huntington’s.This research has already opened upnew potential drug targets for the control ortreatment of these conditions.Dale Bredesen, MDProfessorAlzheimer’s DiseaseDale Bredesen, MD, an internationally recognizedexpert in the mechanisms of neurodegenerativediseases, came to the Buck Institutein 1998 as its founding president and CEO. Hisresearch has led to new insights that explainthe erosion of memory seen in Alzheimer’sdisease—insights that are opening the door toa new therapeutic approach.Dr. Bredesen has found that Alzheimer’sdisease stems from an imbalance in nerve cellsignaling—a finding that contradicts the beliefthat Alzheimer’s is caused by the accumulationof sticky plaques in the brain. Several new therapeuticcandidates based on his insights into thefundamental nature of Alzheimer’s disease arecurrently in pre-clinical trials, funded in partby a generous gift of $3.5 million from privatephilanthropist Douglas Rosenberg.Dr. Bredesen is also studying nerve cell signalingin a collaboration between the BredesenLab and BioMarin Pharmaceuticals, Inc.,which is seeking treatments for a rare form ofAlzheimer’s disease—early onset Familial Alzheimer’sDisease (eFAD)—which can developin people as young as 30 years of age.Dr. Bredesen received his MD from DukeUniversity Medical Center in Durham, NorthCarolina, and served as chief resident in neurologyat the University of California, SanFrancisco (UCSF), before joining Nobel laureateStanley Prusiner’s laboratory there as anNIH postdoctoral fellow. He has held facultypositions at UCSF; the University of California,Los Angeles; and the University of California,San Diego. He directed the Program on Agingat the Burnham Institute before joining theBuck Institute.Judith Campisi, PhDProfessorCancer and AgingJudith Campisi’s lab focuses on understandingthe cellular and molecular biology of aging,particularly its relationship with cancer. Herteam explores the causes and consequencesof cellular senescence—when stressed cellsstop dividing—and cell death. In studyingthe effects of DNA damage during normaland premature aging, they have found thatsenescent cells promote inflammation, whichdisrupts normal tissue functions and drivesthe progression of cancer. The lab’s pioneeringdiscoveries are shedding light on anti-cancergenes, DNA repair mechanisms that promotelongevity, molecular pathways that protect cellsagainst stress, and stem cells and their role inaging and age-related disease.Campisi is internationally recognized for hercontributions to understanding why age is thelargest single risk factor for developing cancer.An elected Fellow of the American Associationfor the Advancement of Science, she hasreceived numerous awards, most recently, theLongevity Prize from the IPSEN Foundation.“Aging is controlled by genes andthe environment and poses thelargest single risk for developinga panoply of diseases. Why doorganisms age, and why dothese diseases rise exponentiallywith age? My laboratory aims tounderstand the molecular andcellular basis of aging in mammals.”—Judith Campisi, PhDBuck Institute 2012 Annual Report 37

Faculty ProfilesLisa Ellerby, PhDAssociate ProfessorHuntington’s Disease: Stem Cells,Therapeutic Targets, and TreatmentsLisa Ellerby is an expert on cell death inHunting ton’s disease, an inherited disorderthat attacks motor coordination and cognitiveability. The Ellerby Lab aims to understand themolecular mechanisms causing Huntington’sdisease and to discover therapeutic targets anddevelop treatments for the disease.Scientists in the Ellerby Lab recently correctedthe genetic mutation responsible for Huntington’sdisease using a human induced pluripotentstem cell that came from a patient sufferingfrom the disease. Neural stem cells generatedfrom the corrected stem cells have been transplantedinto a mouse model of Huntington’sand are now generating normal neurons.Ellerby and Buck faculty Robert Hughes havediscovered a new lead on potential drug therapiesfor the disease. They discovered a genemutation that produces an abnormal form ofthe huntingtin protein in a class of enzymesalready implicated in stroke, cancer, and otherdisorders. Ellerby’s work suggests that inhibitingthis class of enzymes may lessen symptomsof Huntington’s disease and prevent nerve celldeath. Further therapeutic targets were identifiedfor Huntington’s disease that involve lipidmetabolism enzymes.Ellerby earned her PhD in chemistry from theUniversity of California, Santa Cruz. She joinedthe Buck Institute in 2000. She was a seniorresearch associate in neurodegenerativedisease and apoptosis and a co-investigatorwith the Program on Aging at the BurnhamInstitute in La Jolla, California.Bradford Gibson, PhDProfessor and Director of the Buck InstituteChemistry and Mass Spectrometry CoreProteomics in Aging, Cancer, andNeurodegenerative DiseasesBradford Gibson established the Chemistryand Mass Spectrometry Core at the Buck Instituteto support research into the molecularbasis of aging and disease. His goal is to identifythe critical biomolecules and the structuralchanges they undergo during normal agingthat allow pathological processes to establishthemselves.The Gibson Lab focuses on understandingthe biological and chemical processes that arecommon to both age-related diseases and aging.The lab’s scientists employ mass spectrometry,protein and carbohydrate chemistry, and structuralbiology techniques to track structuralchanges in aging cells and in age- related diseasessuch as diabetes, breast cancer, and Huntington’sdisease. The Gibson Lab is also part ofa national consortium that is identifying earlyprotein biomarkers of cancer in human plasmathat may yield early diagnostic tests for specificcancers.Gibson received his PhD in analytical chemistryfrom the Massachusetts Institute ofTechnology in 1983 and then took a postdoctoralfellowship in chemistry at CambridgeUniversity in England. Before joining the BuckInstitute in 2000, he was a professor at the Universityof California, San Francisco (UCSF),where he currently holds a joint appointmentas Adjunct Professor of Chemistry and PharmaceuticalChemistry.David Greenberg, MD, PhDProfessor and Vice President forSpecial Research ProgramsCerebrovascular DiseaseDavid Greenberg, MD, PhD, studies the innateresponses that protect or repair the brain aftera stroke. He hopes to uncover new treatmentsthat can mimic and enhance these responses.After a stroke, the brain responds by boostingthe production of proteins that help cells tosurvive or tissues to regenerate. The GreenbergLab is exploring the actions of two protectiveproteins—neuroglobin and VEGF, or vascularendothelial growth factor.One of the most encouraging recent discoveriesin neurobiology is the finding that newnerve cells can be born in the adult brains ofmammals. Dr. Greenberg has shown that newneurons can arise as a response to stroke, andhis lab has identified factors that promote this.He is also working with Buck colleagues on celltransplantation as a therapy for stroke.Dr. Greenberg is Vice President for SpecialResearch Programs at the Buck Institute. Afterreceiving his MD and PhD from the JohnsHopkins University School of Medicine, hetrained in internal medicine at New YorkHospital–Cornell University Medical Centerand in neurology at the University of California,San Francisco (UCSF). Before joining theBuck Institute in 1999, he was on the faculty ofthe Department of Neurology at UCSF and atthe University of Pittsburgh.38 Buck Institute 2012 Annual Report

Faculty ProfilesRobert Hughes, PhDAssistant ProfessorMolecular and Chemical Biology ofAging and NeurodegenerationRobert Hughes explores the mechanisms ofnormal aging in healthy adults and in peoplewith Huntington’s disease. His team in theHughes Lab is searching for compounds thathelp preserve protein configurations in agingyeast cells, and investigating the systems thatmaintain the ability of proteins to fold into theshapes that best support healthy functioning.They aim to discover clues to similar functionsin human cells.Hughes has collaborated with Buck colleagueLisa Ellerby to find new molecular targetsfor potential drug therapies for Huntington’sdisease, a progressive genetic disorder thatdestroys nerves, impairs movement, and causescognitive decline. Hughes discovered that aset of enzymes implicated in stroke and cancermay also support the onset and progression ofHuntington’s disease.Hughes received his PhD in biology from YaleUniversity. He completed postdoctoral fellowshipsin biochemistry and genome sciences atthe University of Washington in Seattle, wherehe worked in the laboratory of Stanley Fields,PhD, a pioneer in yeast technology. As anassistant professor in the Division of MedicalGenetics at the University of WashingtonMedical School, Hughes developed yeast-basedmodels of human genetic disorders. Beforejoining the Buck Institute in 2005, he wasDirector of Therapeutic Biology at ProlexysPharmaceuticals in Salt Lake City, Utah.Henri Jasper, PhDProfessorEnhancing Stem Cell Function toPromote LongevityHenri Jasper has made seminal discoveriesabout the effects of aging on stem cell behaviorand the role of stress in regulating stem cellfunction. The Jasper Lab aims to discover howstress and aging influence the ability of stemcells to self-renew, and whether improvingstem cell activity can influence the agingprocess in multicellular animals. Jasper’s teamis expanding its research on stem cells andthe process of regeneration in the intestinesof fruit flies (Drosophila) to the tracheal stemcells of mice.The Jasper Lab is also studying the networksthat control metabolic homeostasis andinfluence lifespan. The lab’s scientists use thedeveloping retinas of fruit flies to study stressinducedcell death and to identify molecularand cellular mechanisms governing tissuerecovery after stress-induced damage to thegenome.Jasper received his PhD from the Universityof Heidelberg and the European MolecularBiology Laboratory. He became a researchassistant professor at the University of RochesterMedical Center in 2003, and an assistantprofessor of biology at the University ofRochester in 2005. In 2008, Jasper received aSenior Fellow Award of the Ellison MedicalFoundation. He received a Glenn FoundationAward for Research in Biological Mechanismsof Aging in 2010. His research is supported bythe American Federation for Aging Research,National Institute of Aging, National EyeInstitute, National Institute of General MedicalSciences, New York Stem Cell Initiative, andEllison Medical Foundation.Pankaj Kapahi, PhDAssociate ProfessorNutrition and Energy Metabolism inLifespan and DiseasePankaj Kapahi’s research confirms the findingthat diet plays a major role in aging, lifespan,and age-related diseases. Scientists in theKapahi Lab explore molecular mechanismsin a search for strategies to extend healthylifespan in people. Their research involvesusing a combination of biochemical, genetic,and genomic techniques on both the fruit fly(Drosophila) and the nematode worm(Caenorhabditis elegans).The Kapahi Lab found that a low-protein dietcould lengthen the lives of fruit flies. The dietactivated genes that lead to greater energyproduction in the cells’ powerhouse units,the mitochondria, and thus compensated forthe cells’ age-related decline in performance.Humans share the cellular mechanisms thatlink diet to longevity in fruit flies, and thebenefits of dietary restriction are seen acrossall species. Kapahi was the first to demonstratethat the growth-signaling pathway called theTOR pathway, which is involved in cancerand diabetes, mediates the effects of dietaryrestriction.Kapahi, who joined the Buck Institute in2004, earned his PhD at the University ofManchester in England and completed postdoctoralstudies at the University of California,San Diego, and at the California Institute ofTechnology. He has received numerous honorsand awards, including the Ellison MedicalFoundation New Scholar award, the Eurekaaward from the NIH, and the Nathan ShockNew Investigator Award from the AmericanGeronotological Society.Buck Institute 2012 Annual Report 39

Faculty ProfilesBrian Kennedy, PhDPresident and Chief Executive OfficerFrom Invertebrates to Mice toExtending Human HealthspanBrian Kennedy’s innovative work in the biologyof aging began when he was a doctoralstudent at the Massachusetts Institute of Technology(MIT). Under the guidance of MITProfessor Leonard Guarente, he contributed togroundbreaking studies showing that a classof proteins called sirtuins influence aging.He now studies the pathways that modulatelongevity in model organisms ranging fromyeast to humans. A major focus of his currentresearch is the target of rapamycin (TOR)pathway, which has been generating excitementsince it was shown that the drug rapamycincan extend the lifespan and healthspanof mice.Determining whether pathways like TOR canbe regulated to treat the diseases of aging is agoal of the Kennedy Lab, which focuses oncardiovascular disease and metabolic disorderslike type 2 diabetes. Kennedy’s team also studiesthe genetic mutations underlying Hutchinson­Gilford Progeria Syndrome, a rare disorderthat resembles premature aging.Kennedy earned his PhD in biology at MITand completed postdoctoral training at theMassachusetts General Hospital Cancer Centerin Charlestown, Massachusetts. He wasan associate professor in the Department ofBiochemistry at the University of Washingtonin Seattle when he was appointed Presidentand CEO of the Buck Institute in 2010. Hecurrently serves as co-editor-in-chief of AgingCell, the most highly regarded journal in theaging field, and is a regular consultant in thepharmaceutical and biotech industries.40 Buck Institute 2012 Annual ReportDeepak Lamba, mbbs, PhDAssistant ProfessorStem Cell Technologies forAge-Related Eye DisordersDeepak Lamba, a practicing physician fromIndia, is one of the pioneers in the technologyof making retinal cells from human embryonicstem cells and induced pluripotent stem cellsin a laboratory dish. He has shown that retinalcells can be transplanted into the eyes of blindmice and rats and that after transplantation thetreated eyes respond to light.The Lamba Lab is researching new methods totreat macular degeneration, retinitis pigmentosa,and glaucoma using stem cell technology.Dr. Lamba’s lab is concentrating on the longtermefficacy and safety studies that are essentialbefore this form of therapy can be offeredto patients. Developing new approaches tocreating patient-specific stem cells is anothergoal. Lab scientists can now reprogram skincells into embryonic stem cells and then convertthem to retinal cells—a technology thatwill result in a better understanding of visiondiseases and lead to new treatments and drugsto halt, prevent, or delay the onset of thesediseases.Dr. Lamba earned his medical degree from theUniversity of Mumbai, India, and practiced asa physician there before moving to the UnitedStates, where he received his master’s degree inbioengineering from the University of Illinois,Chicago. He did his doctoral thesis and postdoctoralwork on generating and transplantingretinal cells derived from human embryonicstem cells and iPS cells at the University ofWashington in Seattle.Gordon Lithgow, PhDProfessor andDirector of the Interdisciplinary ResearchConsortium on GeroscienceMolecular Mechanisms of AgingGordon Lithgow’s work sheds light on the mechanismsof aging by identifying agents that extendlifespan or prevent age-related disease. Utilizingthe microscopic nematode worm (Caenorhabditiselegans), scientists in the Lithgow Lab havediscovered various factors that lengthen the livesof these animals, and they are applying thesefindings to studies on human cells.Stress has emerged as a major factor in agingand disease, contributing to a breakdown in anorganism’s ability to maintain optimal molecularstability. Maintenance of homeostasis in theface of stress is a common feature of increasedlongevity and healthspan. The Lithgow Lab hasmade seminal discoveries in the use of smalldrug-like molecules to promote homeostasis.Lab members have found compounds thatsuppress the pathology associated with Alzheimer’sdisease. They are currently researchingadditional sets of compounds that extendlifespan and healthspan.Lithgow received his PhD in genetics fromthe University of Glasgow, Scotland. Beforejoining the Buck Institute in 2001, he was asenior lecturer in molecular gerontology at theSchool of Biological Sciences at the Universityof Manchester in England. He directs the BuckInstitute’s Interdisciplinary Research Consortiumon Geroscience.“One theme continues to emergefrom our work—that aging anddisease stem from commonmechanisms. Delaying disease bydelaying the aging process is aserious proposition.”—Gordon Lithgow, PhD

Buck Advisory CouncilChair of BuckAdvisory CouncilHarlan KleimanTrustee, Buck Institute forResearch on AgingCEO, Self Health NetworkSan Francisco, CABAC MembersTarek AbuZayyadPartner, Head of Merchant Banking,Stanhope Capital LLPLondon, UKHussam Abu IssaVice Chairman and COO, SalamInternationalQatarCinzia AkbaralyFounder, Akbaraly FoundationHonorary General Counsel of Italy inMadagascarGroupe SIPROMADMadagascarJames A. AleverasInvestment Advisor Representative,J.P. Morgan Securities LLCSan Francisco, CAKrikor BezdikianCo-founder, MancoLos Angeles, CAJeff BohnsonCEO, AnswersMedia, Inc.Chicago, ILNajib CanaanPrincipal and Chief Investment Officer,Marinus Capital Advisors LLCStamford, CTMehmet CelebiPartner, Illinois Office, Arti Bir Group,Founding Partner, Investments,ConstructionNaperville, ILMark CutisChief Investment Officer, Abu DhabiInvestment CouncilUnited Arab EmiratesMazen S. DarwazehChairman of Board of Directors,Hikma Pharmaceuticals PLCJordan“Belonging to the Buck Advisory Councilexposes me to a new space of researchthat will undoubtedly impact the worldpositively. It is a place where we can allmake a difference.”—Mehmet Celebi, Founding Partner, Arti Bir GroupShahab FatheazamTrustee, Buck Institute for Researchon AgingManaging Director and Head ofthe Healthcare Group, LincolnInternational LLCChicago, ILDarla Totusek FlanaganGeneral Partner, MKD InvestmentsSan Francisco, CAAnthony GhorayebChairman and CEO, G&G CapitalGroupChicago, ILJames W. HarpelSenior Partner, Palm Beach CapitalWest Palm Beach, FLDato Fawziah Abdul KarimCEO, SSU Management ServicesMalaysiaVeena PanjabiVice President and Co-Owner, WorldIndustriesMiami, FLThomas PetersPresident and CEO, MarinCommunity FoundationNovato, CAMary PolandRoss, CADouglas RosenbergKentfield, CARashid SkafPresident and CEO, AMX CorporationRichardson, TXDelly TamerChief Executive Officer,Letstalk.comSan Francisco, CALady Jamileh KharraziChairman, Jamileh KharraziCharitable FoundationUnited KingdomThomas D. WeldonChairman and Managing Director,Accuitive Medical VenturesFernandina, FL and Duluth, GARon LandesFounder and President, LandesBioscienceAustin, TXDavid WetherellManaging Partner, Burrill &CompanySan Francisco, CAWissam ArissFounder and Chairman of the Board,Star GoodsLebanonMikhail BatinExecutive Director, Science forLife Extension FoundationMoscow, RussiaJames EdgarBoard Chair, Buck Institute forResearch on AgingFounding Partner, Global BrandPositioning LLCKentfield, CADavid EliasPrincipal, Alesco AdvisorsEast Amherst, NYPatte McDowellFounder and Board Chair, Cloud NineFoundationSan Francisco, CACatherine H. MunsonTrustee, Buck Institute for Researchon AgingPresident, Lucas Valley PropertiesNovato, CAE. Packer WilburChairman, Southport PropertiesSouthport, CTWilliam E. WolfCEO, BW Capital PartnersChicago, IL44 Buck Institute 2012 Annual Report

the time has come for building upon a greatfoundation of charitable commitment and givingThe community of donors to the Buck Insti tuteexpanded in 2011 to include the Buck AdvisoryCouncil; 10 new trustees; scores of new members,corporate sponsors, and foundations;and a remarkable group of individuals who providedgifts to name the interior spaces at the Buck campusand chairs in the Drexler Auditorium. Last and certainlynot least, there were those who included the BuckInstitute as a beneficiary of their will or honored friendsand loved ones with a testamentary gift in their name.Together, this diverse group helped to ensure the stabilityof the Institute by providing crucial funds foroperations, facilities, faculty recruitment, equipment,educational and public programs, building expansion,and new research.To accomplish our goals of growth, stability, recognition,and visibility, and to address the urgent needfor basic biological research in aging and chronicdisease, the Buck must broaden and deepen its sourcesof support.Often misunderstood, the Buck’s financial pictureincludes a very important annual contribution fromthe founding Buck Trust. This contribution comesthrough the Marin Community Foundation, whichalso supports the Buck Institute for Education andAlcohol Justice, formerly known as the Marin Institute.A fundamental part of the Buck Institute for Researchon Aging, the Buck Trust accounted for 12% of ourtotal income, or $5.7 million.Each of the 19 laboratories at the Buck focuses on aseparate, compelling area of geroscience research. Weare reaching out to connect that research to those forwhom it matters most.In the year ahead and with the Buck’s new state-ofthe-artfacility for the study of regenerative medicinecompleted, the fundraising priorities are clearly therecruitment of faculty, the acceleration of currentresearch, and the funding of educational programs forchildren and adults. Each of these areas offers muchpromise for the Buck Institute to contribute to thefield, increase knowledge, and deepen our connectionto Marin County and the San Francisco Bay Area,where philanthropist Beryl Buck lived and dedicatedherself to the well-being of others.The time has come to build upon the great generosityand commitment of our past and current donors andto realize the exciting promise of our mission to extendhealthspan through research and education.Buck Trust Income as Percentage of Total RevenueWith a rapid decline in funding from the NationalInstitutes of Health (NIH) brought on by stagnatingbudgets and the increased costs of the science theNIH does fund, the Buck Institute must look to individualdonors to bridge the gap. Individual donorsunderstand and are inspired by the range of work, theinnovation, and the collaboration that are part of theunique fabric of the Buck. While some are taken withthe founding idea that aging and chronic diseases arelinked in a causal relationship, others are drawn tothe Buck by a personal interest in a particular disease.OtherRevenueBuck TrustAllocation82%18%FY200876%24%FY200978%22%FY201085%15%FY201188%12%FY2012Buck Institute 2012 Annual Report 45

Financial StatementSStatement of Net AssetsJune 30, 2012(With Summarized Comparative Information at June 30, 2011)2012 2011AssetsCash $ 703,309 $ 2,595,991Grants and contributions receivable, net 7,488,949 8,792,951Accounts and interest receivable 42,909 74,744Investments and investments held in trust 14,652,485 16,801,847Notes receivable 477,752 246,393Charitable remainder trusts receivable 817,422 799,091Deposit and other assets 504,189 737,257Bond issuance costs, net 1,099,695 1,141,726Property and equipment, net 108,693,786 86,854,073Total assets $ 134,480,496 $ 118,044,073LiabilitiesAccounts payable and accrued expenses $ 4,752,829 $ 5,196,166Deferred revenue 4,892,500 2,671,098Accrued interest payable 6,719 72,285Notes payable 6,616,299 3,630,820Bonds payable 80,600,000 80,600,000Total liabilities 96,868,347 92,170,369Commitments and contingenciesNet assetsUnrestricted 33,249,612 22,723,410Temporarily restricted 4,268,417 3,055,904Permanently restricted 94,120 94,390Total net assets 37,612,149 25,873,704Total liabilities and net assets $ 134,480,496 $ 118,044,073$40$35$30$25$20$15$10Increases in Grant Revenue(in $millions)$21.4$17.8$18.9$28.3$4.9$23.4$39.7$15.6$24.1CIRM InfrastructureRevenueGrant Revenuewithout CIRM$50FY2008FY2009FY2010FY2011FY201246 Buck Institute 2012 Annual Report

Statement of Activities and Changes in Net AssetsYear Ended June 30, 2012(With Summarized Comparative Information for the Year Ended June 30, 2011)TotalTemporarily PermanentlyUnrestricted Restricted Restricted2012 2011Operating revenues, gains, andother supportAllocation from the Buck Trust $ 5,689,335 $ - $ - $ 5,689,335 $ 5,764,910Grant revenues 39,659,898 - - 39,659,898 28,298,550Contributions 1,591,820 2,002,117 - 3,593,937 3,013,044Interest and investment income 55,998 - - 55,998 78,753Other income 244,538 - - 244,538 129,516Net assets released from restrictions 808,205 (808,205) - - -Total operating revenues, gains,and other support48,049,794 1,193,912 - 49,243,706 37,284,773Operating expensesResearch 24,726,376 - - 24,726,376 23,434,857General and administrative 9,568,513 - - 9,568,513 8,365,916Fundraising 1,991,585 - - 1,991,585 1,907,013Bond interest and related costs 1,237,118 - - 1,237,118 1,440,821Total operating expenses 37,523,592 - - 37,523,592 35,148,607Change in net assets from operations 10,526,202 1,193,912 - 11,720,114 2,136,166Non-operating activitiesChange in value of split-interest agreements, net - 18,601 (270) 18,331 129,436Total non-operating activities - 18,601 (270) 18,331 129,436Change in net assets 10,526,202 1,212,513 (270) 11,738,445 2,265,602Net assetsBeginning of year 22,723,410 3,055,904 94,390 25,873,704 23,608,102End of year $ 33,249,612 $ 4,268,417 $ 94,120 $ 37,612,149 $ 25,873,704Operating and Capital Revenue for FY2012Operating Expenses for FY2012Foundation andOther Grants 8%Corporate ResearchAgreements 4%Fundraising 5%Bond Interest andRelated Costs 3%Contributions 7%Interest andOther 1%Federaland StateGovernmentGrants 37%Buck Trust12%General andAdministrative26%Research 66%CIRM InfrastructureGrant 31%Buck Institute 2012 Annual Report 47

Honor Roll of DonorsSteve PageMandy and Samuel ParkeBarbara PattonLynn and Richard A. PayneGail PerinGrace and Roland PerkinsSteven PerlmutterDonna and Jerry PetersConstance PetersonKen PetronVirginia and Don PierceKelley Baer and Louis R. PozzoMelissa PrandiLois PrenticeProMab Biotechnologies, Inc.Janet and Rudy C. RamirezPhyllis and Steven ReinsteinJoan RingKaren RingCarma RoseLinda RosenRutherford & ChekeneRenee Rymer and Tony ClementinoSamer SaltyNancy Marsh Sangster-De Haanand Robert De HaanReva SaperBetsy and John ScarboroughHermann E. SchnabelGail SchroederBirgitt SchueleAndrea SchultzVirginia and William SchultzMary Barbara ShultzJackson ScottMichele E. ScottNancy and Robert SellersChristopher S. SemlerSusan SeverinShamrock Materials, Inc.Brenda ShankIngrid SheetsColleen and John SilcoxSybil SkinnerDon and Jean SmithJenifer and John SmythHelmut SommerCherie and Gideon SorokinDonna and David SpilmanRodney StockEd StolmanVi and Dick StrainDawna and J. Dietrich StroehPauline L. and John G. StuberSunrunIrving and Marilyn TallmanTony TamerBeverly TannerNancy ThomsonRoxanne ThorntonThree Swallows FoundationSally TilburyBerit TisellRuthellen TooleTrison Construction, Inc.Turck, Inc.UnionBankCharlotte S. and Donald F. UrbanRon VinerAaron VollrathLorraine and Vartan VoskanianMr. and Mrs. J.D. WarrenEvelyn WarrenMartha A. and Douglas A. WattAnn and Mark WeinstockSusan WheelerEllen White and Ronald F. GainesKay C. and Rick WhiteSvetlana and Tommie WhitenerPeggy and Charles WilsonShannon Wilson and Janine GuillotPat and John WithersJudy V. and Donald E. WolfGerold C. Wunderlich“My late husband, S. William Levy, MD, was a consultantto the Buck Institute since its inception. He immediatelyrecognized the importance of such a research facility.Now we, the family, carry on his legacy and give continuedsupport to this important endeavor.”—Elisabeth LevyGloria and Peter YuMerla Zellerbach and Lee MunsonCareen Zelli and Joseph AntounUnder $250AA Electric SE Inc.Judy and Paul ArchambeauLinda D. and Ted N. BakerLois BallSusan T. BallingerKenneth BaumanNeil BaumanShirlyn and David BaumanPatricia and Donn BeardenMarie Cressey BeldenRandi and Robert BelsheMarjorie L. BertolinoJosephine and George BlagdenJanet A. Blasi HayssenMark BrandtHelen V. and Frederic L. BrenlinBarbara C. CarterChi-Hui ChaiRichard ChanElaine and Ken ChewPatricia and Melford ChudacoffJanet and Stanley ClarkNancy CoitCarolyn CollinsAnne CorwinCosmosCotati TerminalJanice and Richard CottonRobert B. CrankshawCross Stitch CupboardVirginia CunninghamJanet DaveiroNancy L. and Raul G. DiezAmy Flannigan DittmerDiane DorfmanJean and Kevin DowlingCarrie A. DriscollCharles A. DunkelAnn Eckelhoff50 Buck Institute 2012 Annual Report(§ Board of Trustees Member; *Buck Advisory Council Member)

Honor Roll of DonorsEckhoff Accountancy CorporationCharmaine Eng-NginLetty and Orville ErringerA.S. ErwinKathleen and Dick EschlemanKristi EvansKit EvertsGeorge L. FernbacherDon FerrellElizabeth and Robert FinerPoppy H. FinstonGraham ForderHelen and Jacob J. FosterSally J. and Thomas A. FreedMadelon and Roger R. FrossClara Pearl FuscoSolange and Andre GabanyGail S. and Marc GoldynePatricia and Joseph A. GrysonIlse GudehusEvelyn and Leo GurevitchDouglas HamiltonBJ and Steve HansenGlenne HardingAnita M. and William DennisHasslerElizabeth and Jack R. HeinzHelen A. HeitkampHelen HennessyGloria and Donald HerzogAnn L. HeurlinBarbara HoffmanMary M. and John R. Hofmann Jr.Helyse HollanderLillian B. JarvisBetty and Gene JemailRuth KaganJoyce KamiKB ElectronicsRae and Robert B. KeatingDiana and Milt KellyClaire and John P. KilleenMarion and William KleineckeLeslie Ann and William ThomasKnappBetty Ann KniescheBarbara KrausK. and G. KroneMaria KuesterAlexander KwanAnna and Martin LacknerHelen L. LaHayeMary J. LangPamela and John LarsonBrian LepsisEllen and Victor LevinBeverly Z. and Myron J. LevyJane LuckoffJulia R. MarquetteEd McCooeyJohanna McMichaelJoanne and Bob MillumDona Moberly and John P. TaylorKatherine B. MohrPhyllis and John MuellerScott NelsonKarla NoyolaAnn W. OcheltreeOpperman & SonBetty H. PalkowskiClaire A. Pass“I have had the privilege of supporting the Buck Institutefrom its modest beginnings. With outstanding leadershipand planned expansion, it has become not only a nationallyrecognized research organization, but a unique resource andtreasure to those of us who live in Marin County.”—Marjorie E. Belknap, MDAngelo PastorinoPeter PelhamNeil B. PetersonNancy and Robert PraetzelBoyd QuinnVida Ray and Ted FreemanRed Lion ControlsCarol RossYvonne RothMoe RubinsteinLois Model RukeyserDixie J. RuudDeborah and Paul SaguesJoan M. ShannonMary Richards Yort ShattuckFumio ShibataLydia B. and Charles A. SloanSmith Ranch HomesPhyllis and Peter SommerGeoffrey SpellbergKathy and Bob SteinbaughSucherman Consulting Group, Inc.Douglas W. SullivanShirley A. SullivanMolly A. Susag and Edward A.WalkerWatcharin TararattanakornEva TellerSandra M. TellerMichael A. ThompsonSally TilburyDonald N. TornbergJudy Tsou and David CarlsonEwa UdingBeverlie M. VandreMarjorie WalterJoyce B. WellsPhyllis and L. Warren WelshGloria D. Wilson and EdwardDermottSusan and Ian R. WilsonPatricia Wong and Ronald E. LokVera M. Young(§ Board of Trustees Member; *Buck Advisory Council Member)Buck Institute 2012 Annual Report 51

Buck StaFF Asof June 30, 2012Brian Kennedy, PhDPresident & Chief Executive OfficerMary McEachron, JDChief Administrative Officer& General CounselRaja Kamal, PhDSenior Vice President forInstitute RelationsNancy DerrVice President, Finance &Chief Financial OfficerKristen Gates, EdDDirector, Postgraduate EducationRemy Gross IIIVice President, Business Development& Technology AdvancementDenise KalosVice President, Wellness ProgramsKevin KennedyDirector,Information TechnologyRalph O’RearVice President,Facilities & PlanningBlair WinnDirector,Resource DevelopmentRowena AbulenciaEmmeline AcademiaPooja AgrawalKazutaka AkagiSilvestre AlavezAlexander AlleavitchMahru AnJulie AndersenSuzanne AngeliArieanna AniesJoseph AntounRobert ArchuletaNathaniel AreceneauxDeepthi AshokAudrisz AsuncionTracy BarhydtRicardo BarreraLakisha BarrettLeslie BelingheriChristopher BenzDipa BhaumikAdrian BivolStaff Origins mapBenjamin BlackwellAkilah BonnerMartin BrandDale BredesenRegina BrunauerLibbie ButlerFrancis ByrnesGabriellee CailingTimothy CamarellaJudith CampisiBernadette CastroLise CastroGreg CenicerozDi ChenShankar ChintaBrent CleggCindee CrawleyJulie CreightonDanielle Crippen-HarmonEvelyn CrivelloSteven DanielsonAlbert DavalosDarcy DavisSonnet DavisFrancesco De GiacomoMarco DemariaOlivier DescampsSeana DoughtyGuiping DuCarlotta DuncanLisa EllerbyShiena EnerioRichard FayJames FlynnJuliette GafniAbirami GanesanThelma GarciaBrittany GarrettTheo GarrettAkos GerencserBradford GibsonOlivia GorostizaJill GrahamDavid GreenbergRobert GuempelLisa GurneyBachir HadidJeong-Hoon HahmChong HeKaren HeinJason HeldDillon HenchJustin HillVictoria HogueJennifer HolcombLynnette HollinsKatherine HughesRobert HughesHenri JasperShelly JenningsLori JensenVarghese JohnDarci KanePankaj KapahiSubhash KatewaShana KatzmanDesmond KellyAmit KhannaBo KhanrasaDemetris KillianYong-Hwan KimJanet KingIda KlangMarysia KolipinskiJennika KrisaJeff KroyerJitendra KumarRemi-Martin LabergeDeepak LambaJoann LassakMatthew LayeJudith LewisJay Lewis-KraitsikBiao LiWai LiChen-Yu LiaoChristopher LieuChandani LimbadGordon LithgowQiuyue LiuSu LiuDaniel LockshonVicky LoelRenee LontzTamara LoomisAllison LorenziMark LucanicVictoria LunyakGregory MacIntoshAlex MadiasJulie MangadaJonathan ManningXiao MaoKarla MarkAlex MatalisRichard MaxwellThomas McBrideMark McCormickCary McDonaldLinda McDougalMatthew McGeeMarie McKinneySimon MelovEduardo MezaJackson MillerKylie MitchellOlga MomcilovicJudith MontoyaJustine Montoya-SackShona MookerjeeSean MooneyAnne NeillRyan NgDavid NichollsRobert O’BrienShannon O’HareMonique O’LearyMichelle OhlsonAdam OrrLisa PalmaDorina PapanikolaouKyungchae ParkAlexander PatentOliver PedersenOphelia PedersenJun Peng52 Buck Institute 2012 Annual Report

Buck StaFFJuniper PennypackerIrina PerevoshchikovaTheodore PetersClare Peters-LibeuChristopher PlaceRobert PlaceTodd PlummerChris PobreJordan PoinsettKaren PoksayDeborah PostMilena PriceCasey QuinlanSubramanian RajagopalanArvind RamanathanAnand RanePadma RaoRammohan RaoMatthew RardinMaryanne RavanoKris RebillotJohn ReederLorri ReindersBrandon ReitzelJoseph ReynoldsArmelle RichardIlan RiessChristine RobbinsJennifer RodriguesAric RogersTal Ronnen OronDaniel RothschildAlex SabogalRichard SafrenoMelissa SarantosBirgit SchillingGary ScottChester SeligmanAtossa ShaltoukiTong ShiMasha ShifsAlmas SiddiquiMara SinatsJoanna SitzmannRenuka SivapathamDylan SorensenPatricia SpilmanSteve SpustaTara SrinivasanTom StarrJoel SungaMolly SusagAnna SwistowskaBrandon TavshanjianVeena TheendakaraJonathan ThompsonJanita ThusbergMarc TingJames TollerveyCendrine TouretteShih Yin TsaiMitsuhiro TsuchiyaScott TsuchiyamaStelios TzannisJoanne Van Kampen-JohnsenMiguel VargasMichael VelardeAndrew VinsonCatherine VitelliAlicia WallaceDarrain WatersAdrianne WilliamsonJoy WilsonKathleen Wilson-EdellJustin WinsteadTobias WittkopSun Won KimLin XieBridget YatesHoi Sze YauMariya YevtushenkoKhan ZafarChris ZambataroXianmin ZengNingzhe ZhangQiang ZhangYiqiang ZhaoYing ZouArtem ZykovichDesign: Tobi Designs; Writing: Virginia Kean; Photography: Richard Morgenstein, Robert Vente, Dan Dry, Kristen Gates, and Martin Klimek;p. 1 neuron image by Ludovic Collin/Wellcome Images

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