Buck Institute for Research on Aging 2012 Annual Report

the time has come 2012 annual report

Age-related disease is arguably the single greatest challenge for biomedicine in the 21st century.

And for governments around the world, the greatest challenge may be the tidal wave of health and economic impacts caused by rapidly aging populations.

Through a remarkable convergence of events, the Buck Institute for Research on Aging is now positioned to take a central role in addressing this global health crisis.

The time has come for the Buck Institute to fulfill its founding promise to increase healthspan—the healthy years of human life.

4  Buck Institute 2012 Annual Report

the time has come

2012 annual report

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

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the buck index 2012 1 in 8 71% 250% 80% 50% two-thirds 95%

Number of people worldwide who will be age 65 and older by 2030:

1

Growth rate of older populations in developed countries between 2010 and 2050: growth rate in less developed countries:

2

Percentage of older Americans living with one chronic condition: percentage living with at least two:

3

Portion of United States’ health care costs used to treat chronic diseases:

Percentage of older Americans’ health care costs spent to treat chronic diseases:

4

5

Percentage that the lifespan of healthy nematode worms is extended when exposed to Thioflavin T, a common laboratory dye:

50%

6

1 1 in 8

Rank of the United States of per capita health expenditures in the world: Chance that an American age 65 or older has Alzheimer’s:

7

8

Expected increase in Alzheimer’s disease costs in the United States between 2011 and 2050:

$183 billion to $1.1 trillion

9

21–25% 1 in 2 32% 77%

Percentage that weekly moderate exercise reduces the risk of developing breast and colon cancers: Chance that a woman in a high-income country is sufficiently active:

11

Percentage of Americans age 65 and older who did not exercise in the past month: nearly Percentage of all American cancer cases diagnosed in people age 55 and older:

10

12

13

1 National Institute on Aging. “Overview: Our Aging World.” Why Population Aging Matters: A Global Perspective.

6 Alavez, Silvestre, et al., “Amyloid-binding Compounds Maintain Protein Homeostasis During Ageing and Extend Lifespan.” Nature 472 (2011): 226–229.

2 National Institute on Aging. “Humanity’s Aging.” Global Health and Aging.

7 World Health Organization. World Health Statistics 2012. (Geneva, Switzerland: World Health Organization, 2012).

3, 19 National Center for Chronic Disease Prevention and Health Promotion, Division of Adult and Community Health. “At a Glance 2011” Healthy Aging: Helping People to Live Long and Productive Lives and Enjoy a Good Quality of Life.

4, 5, 12 Centers for Disease Control and Prevention and the Merck Family Foundation. The State of Aging and Health in America 2007.

6 Buck Institute 2012 Annual Report

8, 9 Centers for Disease Control and Prevention. The CDC Healthy Brain Initiative: Progress 2006–2011. (Atlanta, GA: Centers for Disease Control and Prevention, 2011).

10, 11, 16, 21, 22, 24 World Health Organization. Global Status Report on Noncommunicable Diseases 2010. (Geneva, Switzerland: World Health Organization, 2011).

the buck index 2012

Lifetime risk of developing cancer for an American man:

1 in 2 1 in 3

14

Lifetime risk of developing cancer for an American woman:

15

Percentage of cancers that can be prevented by improving diet, physical activity, and body composition:

27–39%

16

Percentage that Buck CEO Brian Kennedy believes laboratory research will extend the human healthspan:

41% 28% one every minute

Expected percentage of Americans living with cardiovascular disease in 2030:

17

18

Percentage of deaths caused by heart disease in Americans age 65 and older: Frequency that an American dies from a coronary event:

15%

19

20

Number of deaths that could be prevented each year worldwide if salt consumption were reduced to recommended level:

2,500,000

21

Percentage of the world’s adults who are overweight:

35% 27% 22

Percentage of Americans age 65 and older living with diabetes:

23

Percentage that engaging in weekly moderate physical activity reduces the risk of developing diabetes:

82% 90% 46% 12%

Percentage of the world’s blind people who are age 50 and older:

Percentage increase in the lifespan of nematode worms when treated with lithium:

13, 14, 15 American Cancer Society. Cancer Facts & Figures, 2012. (Atlanta, GA: American Cancer Society, 2012).

17 Buck Institute for Research on Aging. Buck Institute Helps Launch National “Healthspan Campaign.”

18 Heidenreich, Paul A., et al., “Forecasting the Future of Cardiovascular Disease in the United States.” Circulation. E-pub January 24, 2011.

20 Lloyd-Jones, Donald, et al., “Heart Disease and Stroke Statistics—2010 Update: A Report from the American Heart Association.” Circulation 121 (2010): e46–e215.

24

25

Percentage of visually impaired people who live in developing countries: more than

Percentage that rapamycin extends lifespan in mice:

27% 26

27

28

23 Centers for Disease Control and Prevention. National Diabetes Fact Sheet: National Estimates and 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 the Elimination of Avoidable Blindness, Action Plan 2006–2011. (Geneva, Switzerland. World Health Organization, 2007).

27 McColl, Gawain, et al., “Pharmacogenetic Analysis of Lithium-induced Delayed Aging in Caenorhabditis Elegans.” Journal of Biological Chemistry 283 (2008): 350–357.

28 Harrison, David, et al., “Rapamycin Fed Late in Life Extends Lifespan in Genetically Heterogeneous Mice.” Nature 460 (2009): 392–395.

Buck Institute 2012 Annual Report 7

Letter from the President

A

stunning percentage of the world’s popu­ lation will be over the age of 60 by 2025. By 2050, the percentage will be 41.5% in Japan, 33.9% in China, and 26.6% in the United States. No surprise, then, that there is a growing global health crisis as a result of these rapidly aging popula­ tions, the chronic diseases associated with aging, the inadequate support services in nearly every country, and the lack of agreement about how aging and disease are linked.

The Centers for Medicare and Medicaid Services expect national health expenditures to reach $54.2 billion by 2020 for Americans age 65 years and older.

A study from the Milken Institute determined that chronic diseases will cost Americans $4.2 trillion in treatment costs and lost economic output by 2023. But unless there are changes in what we know about aging and how we treat the aging and increasingly sick popu­ lations among us, that money will be spent inefficiently on treating individual diseases or building new hospi­ tals rather than on disease prevention and researching the mechanisms of aging that are the cause of so many age-related disorders.

The Buck Institute for Research on Aging is creating new global alliances that advance innovation, acceler­ ate research, bring new treatments to market, increase understanding and education, and most importantly, extend the healthy years of life—our healthspan. These goals are urgent and universally important. The effect of even a 5-year extension of healthspan will ripple dramatically throughout global health care networks, economies, political systems, and societies.

The Buck has never been in a better position to effect change in the way people around the world confront the challenges of aging and chronic disease. And now we are an even stronger voice advocating prevention and personal choice as it relates to individual health.

8 Buck Institute 2012 Annual Report

Through numerous new global initiatives and collab­ orations, the Buck is more visible than ever before.

Playing on the global stage for the first time, the Buck is pursuing major opportunities to advance the science and understanding of aging. Now more than ever, we need your financial support to keep this momentum going.

As we have demonstrated during the past year and, indeed, the past decade, the Buck Institute is taking a unique approach to the problems of aging and age-­ related disease by cultivating collaborative thinking and experimentation. We’re attracting and retaining the best scientists with an organizational structure that places research before all else, eliminating bureaucracy and the need for scientists to teach. Our state-of-theart research facility is expanding to accommodate a critical mass of leaders and innovative thinkers in every field of aging research—all working together to address the problems of aging. This environment and approach are fostering critical links between research, translational medicine, and health care policy. And we’re growing a global network that informs our per­ spective and the urgency with which we work.

We are moved to action by the scale of the problems facing us, and we are firmly committed to this direc­ tion in the years ahead. Please join us by supporting our many initiatives, research, and programs.

Brian K. Kennedy, PhD

President and Chief Executive Officer

Letter from the Chair

I

t is my great fortune to represent the Board of Trustees of the Buck Institute for Research on Aging during a period of such remarkable development, growth, and accomplishment. The momentum that has developed since the arrival of Brian Kennedy as President and CEO is evident in the hiring of exceptional new faculty and staff, the building of facilities that foster scientific collaboration, the cre­ ation of the Buck Advisory Council, and the expansion of the Board of Trustees.

Today, more than 12 years after the Buck was founded, the scientific and medical community has come to recognize what we have always known: that an under­ standing of aging processes leads directly to an understanding of the causes of an enormous range of neurodegenerative diseases and other disorders, such as Parkinson’s, macular degeneration, breast cancer, type 2 diabetes, and Alzheimer’s.

The goal of the Buck Institute is to find ways of pre­ venting and treating these diseases and disorders to increase “healthspan”—the years of healthy, active living. Our vision is for the Buck Institute to become a global center for research and information on aging that is as important in its field as the Mayo Clinic is in diagnosis and clinical treatment. Most gratifying in this regard is the increasing number of outstanding scientists who want to come to our Institute.

The success of our scientists in obtaining competitive research grants from the National Institutes of Health (NIH) and other sources has been remarkable, espe­ cially during this period of restricted governmental funding. Many of their accomplishments and expand­ ing international collaborations are described in this Annual Report.

Much has been achieved since our last Annual Report under the leadership of my predecessors, Lew Reid and Catherine Munson. That progress has continued this

year with the addition of 10 new trustees to our Board, broadening our capabilities and perspectives and strengthening our committees.

Of course, much remains to be done if we are to achieve our vision. We receive between $5 and $6 mil­ lion annually from the original Buck Trust, based on a fixed percentage of the Trust’s income. This Buck Trust support launched the Institute and enabled it to get where it is today. To reach the next level, however, we must increase our philanthropic support, both locally and internationally.

We have many philanthropic opportunities that can be tailored to the specific interests of a donor. For example, you could help underwrite research on the cause and prevention of a specific disease, such as Parkinson’s, thereby enabling our scientists to pursue a promising line of research not otherwise funded.

Alternatively, you could help fund doctoral candidates in a PhD program that we are hoping to launch with the University of Southern California—the first pro­ gram of its kind in aging—or you could help us broaden the scope of our science by supporting the recruitment of a talented researcher in a field of interest.

We are also exploring opportunities for venture philanthropy—something that seems a natural for us since our entrepreneurial spirit and independence give us considerable flexibility in structuring arrangements.

Naturally, we would welcome the chance to explore these ideas and more with you.

James Edgar

Chair, Board of Trustees

Buck Institute 2012 Annual Report 9

Going Global

the time has come for new business networks and partnering

I

n 2011–2012 business development became a top priority in the Buck Institute’s business plan.

The new emphasis arose from a combination of factors—the increasing number of discoveries about the biology of aging by the Buck’s 20 principal investigators and more than 200 scientists, the decline in funding from the National Institutes of Health (NIH), the conclusion of a major Geroscience grant, and the growing need for partners with complementary clinical, regulatory, and manufacturing capabilities.

By the end of the fiscal year, the Business Development and Technology Advancement department included three remarkable individuals with impressive résumés in biology, organic chemistry, drug development, patent application, licensing agreements, and new business entity creation and management. Capitalizing on their expertise, the Buck Institute adopted a vigor­ ous and far-reaching approach to the creation of new opportunities, collaborations, and partnerships with academic institutions, corporations, and nonprofits across the globe.

geographically restricted licensing arrangements, new patent applications, joint research ventures, and the creation of a for-profit entity to produce and distribute new products developed with the Buck’s scientific expertise.

Dedicated to understanding and deepening the world’s knowledge of the aging process in all its complexity, the Buck Institute is now on the threshold of fulfill­ ing its mission to increase healthspan—the healthy, productive years of life. The priority of partnering underscores our determination to push the boundaries of aging science and to accelerate the pace of bringing new therapeutic treatments to aging populations around the world.

Meetings this past year with potential partners in Brazil, Russia, Japan, Hong Kong, Switzerland, Chile, Madagascar, China, Turkey, and many countries throughout the Middle East confirmed an urgent, global need for the Buck’s research on aging and for the therapies poised to emerge from its laboratories. Pro­ ductive discussions ensued on early-stage investments in promising research on the chronic diseases of aging,

“Chronic diseases are a correlate of aging and responsible for more than 63% of global deaths. As a global leader in science, the Buck is taking initiative in health policy-making and promoting innovation in the fields of chronic disease prevention and healthy aging.”

—Professor Joseph Antoun, MD, MS, MPP Adjunct Professor of Health and Public Policy

10 Buck Institute 2012 Annual Report

First Foray into Global Public Policy

I

n the fall of 2011 the Buck Institute welcomed Joseph Antoun as Adjunct Professor of Health and Public Policy. A cross-national/comparative health policy expert, Professor Antoun is helping the Buck explore the possi­ bility of developing a PhD program in aging research and guiding the Buck’s entry into the global debate on health care policy.

“Professor Antoun’s medical and business expertise is allowing us to move into this new sphere of health care policy and join the debate about how this country develops and distributes new drugs,” says President and CEO Brian K. Ken­ nedy. “With the work in our labs and the expansion of our educa­ tional programs, we aim to have a major impact on global health. At the same time, we want to make sure that public policy includes an ‘aging’ perspective.”

Prior to his appointment, Professor Antoun was the public policy and strategic development leader for emerging and developing markets at Eli Lilly and Company. He is President and CEO of Health Sys­

tem Reform S.A.L., a consultancy aimed at improving public health through health policy. Professor Antoun is the co-director of the Center for Health Policy at the University of Chicago where he teaches Health Systems, Pharma­ ceutical Policy, and Leadership in Healthcare. He is also a visiting fellow in the Department of Social Policy at the London School of Economics and Political Science.

Professor Antoun received his mas­ ter’s degree in public policy from Harvard University and his medical doctorate and master’s degree in medical and biological sciences from Saint Joseph University in Beirut, Lebanon. He serves on the scientific advisory board of the Akbaraly Foundation’s 4AWOMAN project, the first national oncology project in Sub-Saharan Africa, and on the Dean’s International Council of the Harris School of Public Policy at the University of Chicago.

BELOW: Brian Kennedy and Joseph Antoun speaking at a community seminar focused on global health care and chronic disease.

Above: Cinzia Akbaraly, the president of Madagascar’s Akbaraly Foundation, receives the BAC Humanitarian Award; Nobel Prize–winning economist Myron Scholes is the recipient of the BAC Award for Scientific Achievement.

Buck Advisory Council Founded in 2011, the Buck Advisory Council (BAC) is a diverse group of women and men from around the world who are committed to supporting the mission of the Buck Institute and serving as its informal global ambassadors. Council members include leaders in venture capital, business, finance, consultancy, law, technology, and other fields of endeavor. Many have served as pillars of their communities and are among the most respected in their professions.

Each year, the BAC convenes a domestic meeting and an international meeting for the purpose of engaging its members with the most recent developments in the fields of aging, disease, and health care. In addition, the BAC presents scientific and humanitarian awards to individuals who demonstrate exceptional accomplishment and dedication in their area of expertise.

Buck Institute 2012 Annual Report 11

Going Global

Above: Fluorescent images of neural precursor cells and dopaminergic neurons generated from human embryonic stem cells.

Global Leader in Revolutionary Stem Cell Technology

O

ne of the most tantalizing prospects in biomedical research is the possibility of using stem cells to replace cells in our brains and other organs that have been damaged by the diseases of aging. From her lab at the Buck Institute, Xianmin Zeng, PhD, is leading a global charge to get a stem cell treatment for Parkinson’s disease ready for clinical trials.

Parkinson’s slowly destroys the dopamine-producing neurons in the brain that control movement.

Zeng says the initial challenge in the search for a stem cell treatment for Parkinson’s was getting the right stem cells to use to replace the

12 Buck Institute 2012 Annual Report

destroyed cells. Zeng had already generated dopamine-producing neurons from human embryonic stem cells when she came to the Buck from the National Institutes of Health (NIH) in 2005. When technology was developed in 2006 to reverse-engineer adult stem cells to become embryonic-stemcell-like cells, she jumped on the opportunity.

But it’s one thing to generate dopamine-producing neurons in a lab dish. It’s another matter entirely to generate a sufficient quantity of clinical-grade neurons for human trials. In the past 2 years, Zeng developed a method to reproduce the required neurons. Also, she

proved that the method could be scaled up and the cells produced in a good manufacturing practice (GMP) manufacturing facility, which is a core requirement for clinical trials.

Zeng’s manufacturing partner is the City of Hope’s GMP manufacturing facility near Los Angeles, Califor­ nia. They have already produced some of the cells, which the Zeng Lab is currently testing to validate that they have the same function as those the lab has produced. In par­ allel with long-term safety studies, including a 9-month test in mice to ensure that the cells do not produce tumors, the design of the clinical trial is under way.

“We are planning and hoping to file an investigational new drug application in the near future. I cannot really tell when we can expect such a therapy, but my hope is for a Phase I trial within the next 5 years.”

—Xianmin Zeng, PhD Associate Professor

Two years ago, the California Institute for Regenerative Medi­ cine awarded a grant to Zeng and her long-time collaborator Dr. ­Mahendra Rao, the director of the Center for Regenerative Medicine at the NIH, to prepare the trial and to work on the basic biology of the disease. With clinician and manu­ facturing partners at University of California, San Francisco (UCSF), the City of Hope, Johns Hopkins University, and the NIH, the two are engaged in defining the criteria that will be used to determine the type of patients most likely to bene­ fit from the new stem cell therapy.

trotting this past year to coordinate stem cell manufacturing proce­ dures so that clinical trials can be run in different countries, includ­ ing Japan, China, Argentina, and Sweden. Argentina’s stem cell con­ sortium, which has an agreement with the California Institute for Regenerative Medicine, has asked Zeng to serve on its scientific advi­ sory board to advise them on the stem cell protocol she developed.

“My collaborators want to be able to work with their own manufacturing facilities, and to decide which pro­ tocol to use. My goal this past year has been to show everyone that we

are one of the first to have verified our data and our protocol in a GMP manufacturing facility.”

At the end of the day, Zeng hopes that the new source of cells will lead to more rapid development of cell replacement therapies for Par­ kinson’s disease, to better under­ standing of the mechanism of the disease, and to testing new drugs that may help Parkinson’s patients in the future. “The global collabora­ tion we are doing will get others the tools they need so that they don’t have to start from the beginning.

This should speed up the search for new therapies.”

Zeng’s work is receiving interna­ tional attention. She has been globe­

Buck Institute 2012 Annual Report 13

Going Global

“If I had not had breast cancer, I would never have had the idea to start 4AWOMAN to fight cancer in Madagascar. It was a chance to do something that would relieve pain and serve the women of this country that I love—women who deserve the same level of respect and dignity that I received.”

—Cinzia Akbaraly President, Akbaraly Foundation

Partnering with Madagascar’s Akbaraly Foundation

I

n 2011 Cinzia Akbaraly, founder and president of Madagascar’s Akbaraly Foundation, invited Chris Benz, MD, to present an overview of the global status of breast cancer at a TEDx Antananarivo event she had organized. Her goal was to call attention to the plight of Madagascar’s women, who were dying of breast and cervical cancers at a high rate.

Having been successfully treated for breast cancer in her native Italy, Akbaraly was passionate to do something about the dire situation of cancer patients in her adopted country, particularly that of the women, the social and eco­ nomic heart of this island nation.

“Madagascar is losing ground very fast,” says Dr. Benz, a practicing oncologist as well as a leading expert on the genetic and structural variations among different breast cancers. “Even though Madagascar has one of the lowest worldwide incidence rates, it has a very high

death rate from breast cancer. And cervical cancer, which we’re essen­ tially eradicating in the United States, is the number-one cancer killer. In Sub-Saharan Africa, by the time a woman gets diagnosed with breast or cervical cancer, 70% of the time it’s in an incurable stage, so she’s essentially going to die.”

The Akbaraly Foundation’s 4AWOMAN project targets these two killers and is working to raise awareness, expand screening, and establish basic infrastructure in Madagascar. “These are first steps, but we really want to partner with them and form a research alliance,” says Dr. Benz.

Apart from the humanitarian reason, there’s a strong scientific reason for collaborating: the need for data on the special type of breast cancer afflicting the women of Madagascar. One of the most aggressive forms of breast cancer is commonly found in African-Amer­ ican women. It lacks biomarkers

14 Buck Institute 2012 Annual Report

that allow for the use of targeted chemical and hormonal therapies, and the pathways driving it are unknown. “Fewer than two dozen indigenous African breast cancers have actually been analyzed in depth,” says Dr. Benz. “We suspect that breast cancers in Madagascar are going to represent an even more aggressive subset of African-Amer­ ican breast cancers, but nobody has any data yet.”

Cinzia Akbaraly became a found­ ing member of the Buck Advisory Council, and that’s how she met Dr. Benz. In 2012 she received the BAC’s Humanitarian Award.

The problem she is tackling is huge—late diagnoses, lack of drugs and access to clinics, few treatment options, no tumor registries, cul­ tural stigmas, and economic and political instability—and the needs are great. “It’s probably going to take longer than my lifetime, but Cinzia’s an impatient person,” says Dr. Benz. “If this can be done at all, it will be done by Cinzia.”

Board Profile

Shahab Fatheazam

Below: Cinzia Akbaraly and Buck faculty Dr. Chris Benz. Akbaraly received the Humanitarian Award at the 2012 meeting of the Buck Advisory Council.

As a managing director of Lincoln International and head of the firm’s Healthcare group, Shahab Fatheazam spends 60% of his time on global transactions. That gives this Buck Institute Board member a unique vantage point for appreciating the role the Institute is poised to play in a world increasingly impacted by aging demographics. “The Buck Institute is at the absolute center of a growing debate that is happening in government, pharmaceuticals, academia, and banking,” he says. “The possibilities are wide open and very exciting. I couldn’t say no when asked to be on the Board last year.”

Fatheazam was educated at Cambridge University in England and earned his MBA at Columbia University. He began his career in the international investment banking department of Kidder, Peabody & Company, where as a “newly minted” vice presi­ dent, he witnessed the IPO of biotech pioneer Amgen. He got hooked on health care. “I saw all the tools and services that were needed to make a health care company a success—it really fascinated me.”

“For women, aging is the single greatest risk factor for developing breast cancer. By understanding the different molecular and genetic subtypes of breast cancer, new prevention strategies can be designed that will eliminate this deadly disease.”

Fatheazam, who makes his home in Chicago, is eager to bring that same fascination and a wealth of experience to the Buck Institute. “The Buck is doing high-caliber science with exemplary faculty and staff,” he says. “I look forward to being part of its future.”

—Christopher Benz, MD Professor and Program Director

Buck Institute 2012 Annual Report 15

Year in Review

the time has come for realizing the promise of regenerative medicine

New Era in Stem Cell Research

I

n April 2012, the Buck Institute celebrated the opening of its Regenerative Medicine Research Center, bolstering its unique efforts to exploit the promise of stem cell technology to advance aging research. The goal is to move more rapidly in developing new therapies to prevent and treat the diseases of aging.

The new research center is a California Institute for Regenerative Medicine (CIRM) Center of Excellence— one of just 12 stem cell facilities approved for funding throughout the state. The citizens of California, through CIRM, are making this urgently needed research possible. In nine laboratories of this state-ofthe-art building, stellar scientists, including two new faculty, are currently collaborating on research and using stem cell technology to detect, delay, prevent, and treat the scourges of aging—Alzheimer’s and Parkinson’s ­diseases, cancer, cardiovascular disease, macular degeneration, and stroke.

The new building, which incorporates many “green” technologies, symbolizes for the Buck the hope and promise of stem cell research. This fitting stage for the Buck’s expanded focus on regenerative medicine would not have been possible without CIRM, which provided half of the funding for the $41 million building. CIRM is also funding some of the stem cell research underway in the Center’s research labs and supporting the crucial training of new stem cell scientists. These investments will benefit Californians and people around the world for years to come.

16 Buck Institute 2012 Annual Report

“We are so proud to have had the opportunity and privilege to fund part of the construction of this new building. We are looking forward to hearing about all of the wonderful research that will come out of this facility.”

—Jonathan Thomas, Chair CIRM Independent Citizens’ Oversight Committee

Left to right: Jonathan Thomas, Chair, CIRM; Brian Kennedy, PhD, Buck Institute President and CEO; Alan Trounson, PhD, President, CIRM; James Edgar, Chair, Buck Board of Trustees.

Above: Model of completed Buck campus. Future funding will enable construction of two additional research buildings approved in the Buck master plan.

Buck Institute 2012 Annual Report 17

Year in Review: new Faculty

Boosting the Regenerative Power of Adult Stem Cells to Enhance Longevity

T

he Buck’s newest faculty member, Henri ­Jasper, PhD, brings an international reputa­ tion as a stem cell biology star to the Institute.

Jasper is renowned for making fundamental discoveries about the role of stress signaling and aging on stem cell behavior.

to study the underlying mechanisms causing retinal diseases such as macular degeneration, a major cause of blindness and visual impairment in older adults. The Jasper Lab will collaborate with the Lamba Lab, which is developing stem cell replacement therapies to treat macular degeneration.

The German-born scientist spent the summer of 2012 relocating his lab—1,500 genetically unique strains of fruit flies (approximately 20,000 individual flies) and six lab members—from the University of Rochester to the Institute’s Regenerative Medicine Research Center.

The Buck Institute was on Jasper’s radar screen as a potential place to work for many years. A visit in 2011 finally convinced him to make the move. “I was struck by the collaborative spirit at the Buck—it really is a unique environment,” says Jasper. “The opportunity to do interdisciplinary work with so many outstanding scientists focused on aging and disease is very exciting.”

Jasper, who received his PhD from the University of Heidelberg in Germany and the European Molecular Biology Laboratory, is focused on enhancing the func­ tion of adult stem cells. As we age, adult stem cells— which live in pockets throughout our bodies and go to work when important tissues are damaged—become less effective. He wants to understand how adult stem cells regenerate damaged tissue and why their regener­ ative potential declines with age.

Jasper was one of the first aging researchers to use stem cells in the intestines of fruit flies to test how aging affects stem cell function. Jasper is also using the retinas of fruit flies to determine how insulin and stress-signaling pathways control tissue regeneration, metabolic homeostasis, and cell death.

“We think the short-lived fruit fly, with tissues and genetics that can be easily manipulated, offers a perfect scientific palette for this inquiry,” Jasper says. While the fruit fly is an ideal model system for his work, he plans to expand his research to mammals, specifically to the respiratory systems of mice, which regenerate from a stem cell population that closely resembles the intestinal stem cells of fruit flies.

Jasper recently received a highly competitive grant of $1 million from the National Eye Institute to continue research on developing the fruit fly as a model to study degenerative eye diseases. He is focusing on the retina, the light-sensitive tissue lining the inner surface of the eye. His aim is to understand the complex cellular processes that kick in when the retina needs to elimi­ nate cellular debris, including the wreckage associated with aging. The funding will enable the Jasper Lab

18 Buck Institute 2012 Annual Report

Jasper has already begun collaborating with the Ken­ nedy and Kapahi labs. The three groups intersect in their interest in the effects of diet and stress on aging, and they plan to explore the effects of metabolic signal­ ing on stem cell maintenance and regeneration.

“It’s the science that counts, and that’s why I’ve come to the Buck. The Institute is poised to make major contributions to the field of regenerative medicine, and I am very excited to be a part of that.”

—Henri Jasper, PhD Professor

Buck Institute 2012 Annual Report 19

Year in Review: new Faculty

Innovating with Stem Cells to Treat Vision Disorders

F

or people suffering from age-related macular degeneration—a disease that progressively destroys central vision—Deepak Lamba, MBBS, PhD, is offering new hope with his stem cell research, which is under way in the Buck’s new Regen­ erative Medicine Research Center.

the eyes of mice. When Dr. Lamba tested the stem-celltransplanted eyes for vision, they responded to light.

“Now I need to determine if there will be any issues with tumor development in the new cells,” says Dr. Lamba. “I also need to ascertain how long the trans­ planted cells survive.”

Vision problems often spark a downward spiral in the health of older people. An estimated 11 million people in the United States alone have some form of macular degeneration, making it the leading cause of vision loss in Americans 60 years of age and older. Dr. Lamba, who joined the Buck Institute in October 2011, is using stem cell technology to identify new methods to combat macular degeneration as well as glaucoma and retinitis pigmentosa.

Dr. Lamba’s work goes beyond developing stem cell replacement therapies. He is using iPSC technology to generate eye cells from skin cells to better understand and prevent, or develop treatments for, diseases like glaucoma. Eye diseases in the glaucoma group often share traits such as high eye pressure, damage to the optic nerve, and gradual sight loss. “Glaucoma is a complicated disorder since it affects the ganglion cells, which project from the eye to the brain,” says Dr. Lamba. “Transplantation would be much more difficult, so I’m using iPS cell technology to create cells that can be used to screen existing drugs in order to identify those that might be useful as a treatment.”

Photoreceptors, Dr. Lamba says, are the key cells needed to treat macular degeneration. As a graduate student, he pioneered the development of efficient methods of making these retinal cells from human embryonic stem cells (hESCs). Taking advantage of new technology, he also derives retinal cells from induced pluripotent stem cells (iPSCs). An iPSC is a cell taken from any tissue that has been reverse-engi­ neered to behave like an embryonic stem cell. Utilizing both hESCs and iPSCs, he has generated differentiated photoreceptors—the cells in the eye that respond to light—and has successfully transplanted these cells into

20 Buck Institute 2012 Annual Report

Dr. Lamba came to the Buck because he wanted to be part of the Institute’s larger focus on delaying the aging process itself. He is studying retinitis pigmentosa, a group of hereditary eye diseases that lead to blindness.

“In many people, the symptoms of the disease don’t show up until age 50 or 60. Delaying the aging process would make a huge difference for these patients.”

“Impaired eyesight often heralds a sharp decline in quality of life for seniors. Losing the ability to read, drive, and safely navigate one’s surroundings can be devastating.”

—Deepak Lamba, MBBS, PhD Assistant Professr

above: 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 discovery

Reversing the Aging Process

W

hat is going wrong with our biological clock as we age? Victoria Lunyak, PhD, and her lab team began searching for answers by hypothesizing that DNA damage in the genome of adult stem cells would look quite different from the age-related damage occurring in 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, skin cells become “new” every 4 weeks, and the cells in our skeleton turn over every 10 years. Adult stem cells also kick into action when tissues are damaged and in need of repair. Unfortunately adult stem cells lose their regenerative powers with age. When this happens, the body no longer replaces the damaged tissue as well as it once could, which leads to a host of diseases.

Much of the damage caused by aging is thought to be a result of cells losing telomeres, the caps found at the ends of chromosomes. But since adult stem cells are known to keep their telomeres, Lunyak suspected that different mechanisms were at play that would explain aging in adult stem cells.

Below: Victoria Lunyak, PhD, Associate Professor.

In a landmark study undertaken with scientists from the Georgia Institute of Technology, University of Cal­ ifornia, San Diego (UCSD), Howard Hughes Medical

22 Buck Institute 2012 Annual Report

Institute, Memorial Sloan-Kettering Cancer Center, International Computer Science Institute, Applied Bio­ systems, and Tel Aviv University, Lunyak’s team at the Buck Institute showed that they can reverse the aging process in human adult stem cells. They accomplished this by suppressing the accumulation of toxic tran­ scripts from retrotransposons, the genetic elements that make up about 42% of the human genome.

“By rewinding the cellular clock in this way,” explains Lunyak, “we were not only able to rejuvenate ‘aged’ human stem cells, but to our surprise we were able to reset them to an earlier developmental stage by up-regulating the pluripotency factors—the proteins that are critically involved in the self-renewal of undif­ ferentiated embryonic stem cells.”

The study’s findings were published in the September 1, 2011, issue of Cell Cycle. If Lunyak’s team can now find a way to keep adult stem cells young, the cells could be used to repair damaged heart tissue after a heart attack, heal wounds, correct metabolic syndromes, produce insulin for patients with type 1 diabetes, cure arthritis and osteoporosis, and regenerate bones.

In its most recent discovery, the Lunyak Lab has found that noncoding RNAs (ribonucleic acids), which make up a large portion of the human genome, provide vital scaffolding for cellular processes in adult stem cells. This finding implies that the chronic diseases of aging arise from the deterioration of this scaffolding rather than from genetic mutations, giving researchers additional targets for therapeutic interventions.

Year in Review: education

Training a New Generation of Scientists

M

ore than a decade ago, Richard Klausner, former Chairman of the National Com­ mittee on Science Education, said, “All of us have a stake, as individuals and as a society, in scientific literacy.” Since then, the need for science education has become critical, especially as the role of the United States as a global leader in technol­ ogy is called into question. In the San Francisco Bay Area, the challenging economic climate facing public educational institutions has made the situation even more difficult. Some schools have been forced to reduce or eliminate courses, extracurricular activities, and teacher training in the sciences.

Providing assistance in this crucial area was at the core of the Buck Institute’s educational outreach in 2011–2012.

The Buck’s mission is to extend healthspan—the healthy, produc­ tive years of life—through research and education. In 2011–2012 the Buck Institute responded to regional needs by expanding its educational programming, which in the previous 3 years had reached 3,000 children. Following the directives of the Presidential Science, Technology, Engineering and Math campaign (STEM), the Buck tailored its educa­ tional programming to enhance the participation and performance of the region’s youth in science and math.

celebration of science that drew 4,000 people to its North Bay Discovery Day main event. The Institute also broke ground on a new, state-of-the-art, 1,500-squarefoot demonstration laboratory and classroom, which will dramatically enhance its ability to provide unique training in science for children and adults.

Throughout 2011–2012, the Buck offered free commu­ nity education seminars for adults. Buck scientists and executive staff visited community and professional groups to speak about the Institute’s research advances and discoveries in aging and age-related diseases. The Institute hosted a program called Science in the City—a series of intimate lunches held at the Olympic Club in San Francisco that introduced Buck scientists and their research to members of the business community.

All of these initiatives reflect the Buck Institute’s dedi­ cation to developing the next generation of scientists.

They also underscore the Buck’s commitment to serve as a regional leader in educating young scientists and the general public, and to sharing the results of our research as broadly as possible—research that offers hope for a healthier lifespan for aging populations everywhere.

The Buck hired its first full-time education coordinator for K–12 as well as a director of postdoctoral educa­ tion. The Institute took the lead in coordinating local activities for the Bay Area Science Festival, a weeklong

Pathways to priming the education pipeline Attract

Retain

Persist

Attach

Algebra Academy

High School Summer Scholars

Undergraduate Interns: 2- and 4-year

Graduate Students: MS and PhD

Invite children to learn The Buck’s Education Program

Bay Area Science Festival

Primary to High School

Choose to keep learning

Lead students to graduate

Continue to STEM careers

Postdoc Trainees

Undergraduate Education

Graduate Education

Professorate/ Industry

Buck Institute 2012 Annual Report 23

Year in Review

Accomplishments July 2011

September 2011

Buck CEO Brian

James Edgar elected

Kennedy visits the

as Chair of the Buck Board of Trustees.

March 2012

May 2012

The Providence

Buck Institute and

Middle East where he

Buck Institute holds

The Greenberg Lab

­Journal runs an op-ed

Biotica collaboration

explores partnerships

Scientific Sympo-

publishes a study

co-authored by

will evaluate rapa-

with pharmaceutical

sium: Stem Cells and

in The Proceedings of

Buck faculty Julie

mycin analogs and

companies, govern-

Aging.

the National Aca­demy

­Andersen, “Are We

other polyketides

ments, and research

The San Francisco

Giving U.S. Infants

in a broad range of

institutes.

ABC affiliate runs a

Too Much Iron?”

age-related disease

Proteome Sciences

models to identify

The Arab Times and

novel therapeutics.

Kuwait Times publish

and the Benz Lab to

January 2012

story on the Buck’s geothermal project.

op-eds by Buck CEO

Buck CEO Brian

develop biomarker

Lunyak study in Cell

Brian Kennedy on the

Kennedy goes to

tests to improve

Cycle, “Scientists

epidemic of type 2

Tokyo and Singapore

breast cancer treat-

Turn Back Clock

diabetes now impact-

to forge connections

ment.

on Adult Stem Cell

ing the Middle East.

between the Institute

Aging.”

August 2011 Buck CEO Brian Kennedy is quoted in The New York Times: “Longer lives for obese mice with hope for humans of all sizes.” The article focuses on a study involving the experimental drug SRT1720.

On August 9, 2011, the Buck Institute was

Buck Board adds four new members: Ned Powell, Shahab Fatheazam, Barbara Morrison, and Larry Rosenberger.

Buck CEO Brian Kennedy is quoted extensively in The Scientist regarding the controversies over the role of sirtuins in lifespan extension and age research.

awarded a patent titled “Small Mole-

October 2011

and biotech and

November 2011

The appointment of

Function” (US Patent

Joseph Antoun, MD,

# US7,994,184 B2).

as Adjunct Faculty

P53 has been shown

marks the Buck Insti-

to have the ability to

tute’s first foray into

promote or retard

public policy.

aging, depending on the context of its regulation and activity.

The inventor is Dale E. Bredesen, MD.

New faculty Deepak Lamba, MBBS, PhD, arrives at the Buck Institute. Macular degeneration is added to the roster of age-related diseases studied at the Buck.

24 Buck Institute 2012 Annual Report

panies.

Buck Institute coordinates North Bay Discovery Day at

February 2012

Infineon Raceway on

Research from the

November 5. More

Melov Lab: A study in

than 4,000 people

Science Translational

attend the signature

Medicine shows mas-

event during the Bay

sage reduces inflam-

Area Science Festival.

mation and promotes

Buck faculty Judith Campisi is quoted in a New York Times article focusing on senescent cells and aging.

cules that Replace or Agonize p53

pharmaceutical com-

growth of new mitochondria following strenuous exercise.

The story gets picked up by several national media—NPR, Bloomberg, and USA Today.

December 2011

Buck CEO Brian

The Kleiman Multime-

­Kennedy goes to

dia Studio opens at

Central America to

the Buck Institute.

set stage for scientific collaborations that

Buck faculty Judith

would bring postdoc

Campisi and Simon

fellows to Buck Insti-

Melov are quoted in

tute labs.

a National Journal article, “Longevity: A

The Costa Rica News

Manual.”

publishes an op-ed

by Brian K. Kennedy, “A Wake-Up Call for Costa Rica.”

of Sciences focusing Ambassador Fay

on modifying scar

Hartog Levin and Lew

tissue following

Reid join the Board of

chronic stroke.

Trustees.

The Buck Advisory Buck Institute

Council meets and

appears on Capitol

bestows awards for

Hill; Buck CEO Brian

scientific and human-

Kennedy helps launch

itarian achievement.

national “healthspan” campaign.

April 2012

June 2012 The Glenn Foundation awards $1 million to

Henri Jasper, PhD,

establish training

hired as new faculty

fellowships in aging

member. Arrives in

research.

the summer from Rochester, NY, and

Steve Burrill and Jim

continues research

Gerber join the Buck

aimed at promoting

Board of Trustees.

longevity by enhancing the activity of

The Ellerby Lab pub­

adult stem cells.

lishes a study in Cell

USA Today runs a

correct genetic muta-

story about the 100th

tion responsible for

birthday of Buck

Huntington’s disease

CEO Brian ­Kennedy’s

in human induced

grandmother in

pluripotent stem

­Louisville, KY. The

cells.

piece features an interview with ­Kennedy about aging research.

The Buck Institute’s new Regenerative Medicine Research Center opens on April 14; the Institute’s first public open house draws 1,000 ­attendees.

Stem Cell—scientists

Buck Institute Publications by Year

Board Profile

Catherine H. Munson

103

Total 1,100

2012 87

98

103

2009

2010

2011

102

82

2006 94

2003

75

2007

2008

85

79

2004

2005

10

41

63

78

1999

2000

2001

2002

Motivation comes in all forms. Most people know Catherine Munson as a Bay Area real estate professional associated with the modern residential housing developer Joseph Eichler. But an opportunity to return to her scientific roots prompted the over-scheduled community activist to join the Board of Trustees of the Buck Institute in 2004. Munson graduated with an MA in microbiology and biochemistry from the University of Nebraska in 1950. She worked in basic research before beginning her career in real estate. “I knew the Buck was involved in revolutionary medical research, and I wanted to be a part of it,” she says. “As I got to know the faculty members, I just caught fire.”

Munson, who is the very active CEO of Lucas Valley Properties, served as Board Chair in 2010–2011.

“Supporting the Buck Institute is now my number-­ one passion and commitment,” she says. “The Institute is the most significant organization in Marin County. Everyone ages—the Buck has a humanitarian mission that is impacting global health.”

Increasing the Institute’s visibility is always on her radar screen. “Those of us who live in the Bay Area are incredibly blessed to have access to these world-class scientists who are working to find real solutions to the demographic challenges that face our society,” says Munson. “I am extremely proud and fiercely enthusiastic to spread the word about their efforts.”

Buck Institute 2012 Annual Report 25

POSTDOC COLLABORATIONS

the time has come for bold science, creative collaboration, and new therapies Postdoc Collaborations—Heart and Soul of Science at the Buck

A

t the Buck Institute, there are few walls, little bureaucracy, no turf wars. It’s an environment designed to encourage collaboration across disciplines—one where eager young sci­ entists can bounce ideas off each other and try novel approaches to solving some of the fundamental prob­ lems in aging science.

In most research organizations it’s the young scientists— the postdoctoral fellows who have completed their PhDs—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 only mentored by outstanding faculty members, but they also have daily opportunities to reach beyond their labs to form synergistic partnerships—collaborations both within and beyond the Buck that will advance knowl­ edge and understanding of the biological processes of aging. Their dedication and discoveries may eventually lead to new therapies for some of aging’s worst mal­ adies—cancer, heart disease, and Parkinson’s.

26 Buck Institute 2012 Annual Report

This section highlights postdoc research collaborations at the Buck. Featured are stories of six young scientists who work in the Andersen, Kapahi, Kennedy, Melov, and Campisi labs. Their laser focus and “big picture” attitude exemplify what drives science and research here at the Buck.

While these six postdocs have expertise in different disciplines and technologies, all are working on proj­ ects involving rapamycin—a drug already tested and approved by the FDA for suppressing the immune system of transplant patients. In 2009, a trio of labs reported that rapamycin—a compound discovered on Easter Island in 1964—extended the lifespan of mice by 12%. Rapamycin’s remarkable ability to delay the aging process in mice and other species, along with its FDA-approved status, makes the drug a source of hope and great excitement in aging research.

Buck Institute 2012 Annual Report 27

POSTDOC COLLABORATIONS

28 Buck Institute 2012 Annual Report

Collaborating on a Parkinson’s Discovery

I

n the Andersen Lab, Almas Siddiqui has been working on Parkinson’s disease research since 2008. She’s trying to determine what oxidative stress does to the neural cells of patients with the disease. Oxidative stress, which produces free radicals and is a normal byproduct of cellular metabolism, increases with age. “And increased production of free radicals can create a state of imbalance,” says Siddiqui, “that may contribute to the cell death associated with Parkinson’s disease.”

Three years ago when she first began working with rapamycin, an immune-suppressing drug currently approved for use following organ transplants, Siddiqui found that there was an improvement in the functions of the mitochondria, the powerhouses of the cells, when she applied rapamycin to a cell culture model of Parkinson’s disease. But what really surprised her was the drug’s effect on parkin, a protective protein whose loss of function is reported in Parkinson’s patients.

“We never expected that, when we gave rapamycin to cells in a dish, we would see an increase in the parkin protein levels because generally rapamycin decreases production of new protein,” says Siddiqui. Why was rapamycin having this positive effect on parkin? To confirm her suspicion that the increase was happening at a different level of gene expression than she had expected, Siddiqui turned to Aric Rogers, a postdoc­ toral fellow in the Kapahi Lab, which has an overall focus on aging and nutrition.

Rogers is an expert in the biology of mRNA trans­ lation—especially as it relates to aging. Translation is the final step of gene expression, when our genetic code prompts the production of proteins. It occurs after individual genes encoded in the DNA have been transcribed into RNA, an intermediate that may or may not be translated into functional proteins. S­ iddiqui knew that the transcripts of the gene encoding parkin had not increased, which suggested that the increased ­levels of the protein might be due to an increase in translation. This could be the case if there were increased

association of parkin transcripts with the machinery that synthesizes new proteins. To address this possibil­ ity, Siddiqui sought Rogers’s technical expertise.

Finding the answer was important because, as Rogers explains, “Rapamycin, the drug used in Almas’s experi­ ment, targets a protein complex called TOR. This com­ plex controls a number of cellular processes, including the synthesis of new protein. The technique that I adapted from translation state array analysis can be used to determine changes in the synthesis of specific proteins like parkin.”

Siddiqui’s finding is important, Rogers says, because “if you can understand where the desired effects of a drug are coming from, you can develop a new drug or com­ binations of drugs that avoid unwanted side effects.

Rapamycin targets TOR, which in turn modulates protein synthesis, but TOR also controls a number of

other cellular processes. Drugs can be used to target just those factors affecting protein production, or other drugs may be added to lessen undesired side effects.”

Their collaborative work on understanding rapamycin’s impact on the protein produced in the cell culture model of Parkinson’s disease points to a potential use of the drug—or analogs of it called rapalogs—as a therapeutic for Parkinson’s disease and other neuro­ degenerative disorders. “There’s a huge emphasis now on drugs that target translation,” says Rogers, “and because rapamycin is already approved by the FDA, it will be much easier to get these rapalogs to clinical tri­ als.” “Parkinson’s is still a big black box,” adds Siddiqui, who is moving her research into mice, “but the future is now much more promising.”

above: The central dogma of molecular biology.

left: In a conversation-fostering space, postdocs Almas Siddiqui and Aric Rogers discuss their joint research project.

Buck Institute 2012 Annual Report 29

POSTDOC COLLABORATIONS

Exploring Rapamycin’s Effect on Heart and Bone Health

P

ostdoctoral fellows Monique O’Leary and James Flynn are engaged in a collaboration between the Kennedy and Melov labs that aims to evaluate the health benefits of treating mice with the drug rapamycin. Some of the Kennedy Lab’s many projects focus on cardiovascular health and the mTOR pathway—the pathway that rapamycin inhibits and that modulates aging across many differ­ ent organisms. The Melov Lab is providing genomic expertise and technology to this project, and to the entire Institute.

Four years ago Brian Kennedy hired O’Leary as a postdoc in his laboratory at the University of Washing­ ton to study genes involved in aging and age-related diseases in mice. In 2010 Kennedy, now the Buck Insti­ tute’s president and CEO, asked O’Leary to relocate his lab from the University of Washington and to manage it on a day-to-day basis in addition to working on her own research projects. “I study the process of transla­ tion, when proteins are being made within a cell,” says O’Leary. “The TOR signaling pathway plays a crucial role in translation and the aging process.” Flynn is an expert in gene expression, and both scientists work with mice to understand how they age and to explore potential therapeutics for age-related diseases.

Determining a potential use for rapamycin to treat age-related disorders such as osteoporosis and heart disease is a large part of their work at the Buck. In this study, the two postdocs wanted to see what happens on a genomic level to a normal mouse as it ages—what genes are turned on, what genes are turned off, and why the expression of these genes changes over time.

“We want to look at the signaling molecules down­ stream of the actual molecule that’s called mTOR and to understand how the mTOR signaling pathway relays

Above: Using microCT imaging and 3D analysis software, it is possible to “digitally” slice through bones revealing their inner structure.

Shown here are the middle sections of mouse femurs from young mice (left) compared to older mice (center and right, respectively).

This imaging can reveal the effectiveness of a drug in maintaining bone mass. 3D model by Michael Presley.

30 Buck Institute 2012 Annual Report

its signal throughout a cell or within an organism,” says O’Leary. “From previous studies, we knew that rapa­ mycin extended lifespan, but nobody had done any studies to see if it extends healthspan.”

To add a unique approach to their rapamycin study, Flynn was sent to Belgium for extensive training in micro CT imaging—a technique that enables him to get 3D images inside the femurs of mice. The live imaging allowed Flynn and O’Leary to observe the mice 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 various functions in them and analyzing bone structure, heart function, and muscle mass every 3 months. They have also put a group of “old-aged” mice (24 months of age) on a diet that includes rapamycin and conducted a similar examination of cardiovascular health, bone density, and muscle mass.

Based on their experiments, O’Leary and Flynn have co-authored a paper and submitted it for publication.

“The initial results have been extremely encouraging, especially because these older animals are considered senior citizens in their mouse population,” says Flynn.

“We think we’ve identified a large number of genes that are turned on or off in the mice as a result of having had rapamycin added to their diet. We’re also looking at inflammation as one of the factors that is impacted by rapamycin.”

Flynn learned the technique he used to measure inflammation from a postdoc in the Campisi Lab, Remi-Martin Laberge, whose desk is just a shouting distance away from his own. “The ability to go and talk to someone who’s an expert in this aspect of aging is unique at the Buck because there are few places where there are so many diverse experts on the biology of aging,” says Flynn. “It’s really great to be able to go to someone like Remi and get feedback on a part of your project. You can’t be an expert in everything, so being able to collaborate with experts helps move the science forward and accelerate the research.”

Initially skeptical that their time-consuming project would have any unique beneficial results, O’Leary is looking forward to getting their paper published.

“Many labs around the country are studying rapamy­ cin, with an eye toward its potential use in humans.

We are hoping that our paper makes a significant contribution to that body of work.”

Below: Postdocs Monique O’Leary and James Flynn review data from mouse studies involving the drug rapamycin.

Buck Institute 2012 Annual Report 31

POSTDOC COLLABORATIONS

Reducing the Inflammation That Can Contribute to Cancer

R

emi-Martin Laberge and Su Liu, postdoctoral fellows in the Campisi and Kapahi labs, study senescence—the process that occurs when cells lose their ability to divide. The two scientists are now working on a joint project between their respective labs to identify the effects of rapamycin on senescent cells.

Laberge, who earned a PhD at Canada’s McGill University on cancer drug resistance, has been with the Campisi Lab since 2008.

He is immersed in studying the inflammatory processes that are associated with senescence and their impact on the development of cancer. Liu, who is originally from China, joined the Kapahi

Below: Su Liu and Remi-Martin Laberge look at senescent cells that have been treated with rapamycin. The postdocs often work in one of the cell culture rooms near the Campisi Lab.

32 Buck Institute 2012 Annual Report

Lab in 2010 after receiving a PhD in pathology from the University of Rochester where she studied prema­ ture aging in a mouse model.

Pankaj Kapahi and his lab had been studying the role of the target of rapamycin (TOR) on flies and worms in aging, but were considering extending their work to human cells and mice. So when Kapahi suggested to Laberge that he test rapamycin’s effects on mice and human senescent cells, Laberge took up the challenge.

In the Campisi Lab, Laberge began by applying rapa­ mycin to cells that he had forced to senesce by expos­ ing them to ionizing radiation. Laberge saw lower inflammation in those senescent cells. Next Laberge began studying senescent cells that actually stimulate the growth of cancer cells. “When cells senesce, they spew proinflammatory cytokines, and when senescent cells accumulate, their signals lead to chronic inflam­ mation, which drives cancer. The majority of age-related diseases are boosted by chronic inflammation.”

When Liu joined the Kapahi Lab, she began growing human senescent cells in culture along with cancer cells to see what would happen. She found, as predicted by earlier Campisi Lab experiments, that the senescent cells stimulated the growth of the cancer cells, which became more aggressive and invasive. That’s why, Liu says, it’s important in humans to reduce the number of senescent cells and the inflammation they cause.

“The cancer might grow anyway, but it grows faster when the senescent cells are around,” explains Laberge.

“They’re stimulating cells that are not very invasive to become more invasive, breaking the barriers that prevent those cells from migrating into other tissues.”

Liu and Laberge found that rapamycin could block this stimulating effect.

Laberge also found that many cytokines—those inflam­ matory molecules in the blood that slowly increase as people age—are secreted at much lower levels in the presence of rapamycin. The cytokines are secreted by senescent cells and are potentially in the vicinity of can­ cer cells. Since the level of cytokines in blood is associ­ ated with cardiovascular disease and neurodegeneration, he is now interested in “getting rid of senescent cells or tuning down the chronic, low-level inflammation that is specifically induced by senescent cells.”

function, which might explain the differential role of senescent cells in different contexts,” says Liu. “For example, senescent cells in the cancer context are a bad thing, but in the context of wound healing they play a beneficial role. We need to find a way to target different groups of cytokines.”

Chemotherapy drugs induce DNA damage—that’s how they kill cancer cells, says Laberge. “Often when you treat patients with chemotherapy drugs, they don’t just work on the cancer cells. They also affect the surround­ ing normal cells, and that will induce senescence in those cells. This is a big problem because the cancer cells that aren’t killed by chemotherapy will now be fueled by the surrounding senescent cells that were just created.”

Laberge says rapamycin is so far the best tool to come along for identifying pathways associated with healthspan extension. But the compound can cause diabetes and suppress muscle function. To uncouple the positive and negative effects, he and Liu are trying to dissect the molecular pathways that are impacted by rapamycin. “Hopefully we’ll find something that will be much better than rapamycin—something that will specifically enhance rapamycin’s beneficial effects but not enhance its negative effects.”

For Laberge and Liu, their joint project is a perfect example of the benefits of Buck collaboration. Other scientists at the Buck and elsewhere contributed to their work. Working alone, it would have taken the postdocs years to advance their research to where it is today. “Discoveries go faster here because we’re all under the same umbrella of aging,” says Laberge. “We all have the same goals, but we study different aspects of aging. And as we learn more about molecular mech­ anisms in different organisms, we can then apply them to the various disease systems that others are research­ ing at the Buck.”

This past year, Liu and Laberge tested over 200 dif­ ferent cytokines and found that rapamycin did not inhibit all of them, just a group of them. “This is very important because each cytokine has its distinct Buck Institute 2012 Annual Report 33

Geroscience

the time has come for geroscience—from concept to reality to national participation

T

he Buck Institute is the birthplace of gerosci­ ence, a new discipline focused at the inter­ section of normal aging and chronic disease.

The term “geroscience” entered the scientific lexicon in 2007 when the Buck Institute received one of nine Roadmap for Medical Research grants from the National Institutes of Health.

With this grant, the NIH aimed to support research teams that are “addressing health challenges that have been resistant to traditional research approaches.” The $25 million award validated our mission to extend healthspan and our collaborative interdisciplinary research model. It recognized the value of the Buck’s founding objective—to bring together top scientists with highly disparate backgrounds who share a passion for solving the tough, profoundly complex biomedical problems of aging.

In 2012, the formation of a Trans-NIH Geroscience Interest Group (GSIG) underscored the success of our approach. The GSIG includes scientists from some of the 27 research institutes and centers that compose the NIH who are keen to apply the discoveries in aging research to their own research agendas, which often are focused on a particular dis­ ease. One of the GSIG’s goals is to pro­ mote the application of aging research by developing public/private partner­ ships with scientific societies, industry groups, and other research institutes.

At the Buck, we see this growing inter­ est in aging research as the beginning of a groundswell that will accelerate discoveries and speed development of new therapies to prevent or treat the diseases of aging. And our scientists and their laboratories are at the fore­ front, keeping the momentum going.

34 Buck Institute 2012 Annual Report

Geroscience at the Buck Institute

Every faculty member at the Buck Institute is involved in geroscience. While their specialties range across the entire spectrum of age research—cellular bioenerget­ ics, stress biology, epigenetics, regenerative medicine, neurodegeneration, molecular physiology, and bio­ informatics—the Buck faculty share an intense focus on the connection between aging and chronic disease.

Within and beyond their laboratories, the Buck faculty create an atmosphere that supports discovery and thrives on shared knowledge. While each faculty mem­ ber runs their own laboratory and leads their own team of scientists, all are committed to an organizational structure that has no departmental boundaries and little bureaucracy. Brilliant, entrepreneurial, collabora­ tive, and visionary—the Buck faculty are shedding new light on aging and developing novel solutions to some of its most daunting challenges.

AGE-RELATED DISEASE Alzheimer’s Cancer Cardiovascular Huntington’s Macular Degeneration Metabolic Syndrome Osteoporosis Parkinson’s Progeria Stroke

AGING STUDIES

REGENERATIVE MEDICINE

Dietary Restriction DNA Damage Genetic Pathways Mitochondrial Function Oxidative Damage Senesence Translation

Adult Stem Cells Embryonic Stem Cells Induced Pluripotent Stem Cells (iPSCs)

TECHNOLOGY

Bioinformatics Genomics Metabolomics Morphology and Imaging Proteomics

“We have recent evidence that the aging process is malleable, and it has been observed in several animal models that when aging is delayed, so are the diseases and disabilities that normally accompany aging.”

—Dr. Felipe Sierra, GSIG Founder and Director of the National Institute of Aging’s Division of Aging Biology

Geroscience Studies at the Buck

NIH Record, August 17, 2012

Buck Institute 2012 Annual Report 35

Faculty Profiles

Christopher Benz, MD Professor and Program Director

Breast Cancer

“My greatest hope is that our work here at the Buck will allow us to treat Parkinson’s at the earliest possible stage, so treatment can begin before the disease has a chance to progress. That would free patients to live fulfilling lives without major disability.’’

—Julie Andersen, PhD

Julie Andersen, PhD Professor

Parkinson’s Disease Julie Andersen is an expert on Parkinson’s disease—an incurable, progressive neuro­ degenerative disorder that currently affects over 1.5 million people in the United States. ­Pursuing research that is fundamental for developing treatments for this complex ­disease, which causes a progressive decline in movement and muscle control, she has identified early risk factors, such as elevated levels of iron and declining amounts of a protective antioxidant called glutathione, and several novel drug treatments (lithium, flavonoids).

The Andersen Lab examines the role of the pro­ teins that are involved in nerve cell degenera­ tion and is working to identify biomarkers for Parkinson’s that could result in therapeutic interventions in the early stages of the disease.

Anderson is interested in how the aging brain affects disease.

Andersen was a postdoctoral fellow at Harvard Medical School and Massachusetts General Hospital. Prior to joining the Buck Institute in 2000, she was an associate professor at the Andrus Gerontology Center at the University of Southern California.

36 Buck Institute 2012 Annual Report

Christopher Benz, MD, joined the Buck Insti­ tute in 2000 as a founding faculty member. A senior member of the UCSF Cancer Center’s Breast Oncology Program, he set up the uni­ versity’s first laboratory for the study of human breast cancers. Dr. Benz not only continues to treat breast cancer patients at UCSF’s Carol Franc Buck Breast Care Center, but he also is the co-principal investigator of the Buck ­Institute–UC Santa Cruz Genome Data Analy­ sis Center—one of seven national centers in The Cancer Genome Atlas program.

The Benz Lab was among the first to study why age is such an important determinant for the onset and development of breast cancer, why the incidence of breast cancer increases with age, and how the aging process alters breast cancer biology. In a search for personal­ ized treatments for each patient’s breast cancer subtype, Dr. Benz and his team also explore the genetic and structural differences among breast cancer types, as well as new therapeutic strategies.

Dr. Benz helped organize the Marin Women’s Study (MWS). Launched in 2006, the MWS wanted to detect environmental factors, lifestyle patterns, and individual biofactors contri­buting to breast cancer risk in Marin County, where

incidence rates of the ER-positive type of breast cancer are among the highest in the world. By alerting women to the hazards of taking combination hormonal therapy at meno­pause, the MWS was able to document a sharp decline in hormone use and a resulting 33% reduction in new breast cancer cases in the county.

Faculty Profiles

Martin Brand, PhD

Judith Campisi, PhD

Professor

Professor

Energy Metabolism of Cells

Cancer and Aging

Martin Brand is an authority on mitochon­ dria—the energy-converting unit of cells— and their influence on aging and disease.

After receiving his PhD in biochemistry at the University of Bristol in England, he was a postdoctoral fellow at Johns Hopkins Univer­ sity in Baltimore, Maryland; a faculty member at the University of Cambridge; and then a group leader at the Medical Research Council.

At Cambridge, he began collaborative studies with Buck faculty. He joined the Buck Institute in 2008.

Judith Campisi’s lab focuses on understanding the cellular and molecular biology of aging, particularly its relationship with cancer. Her team explores the causes and consequences of cellular senescence—when stressed cells stop dividing—and cell death. In studying the effects of DNA damage during normal and premature aging, they have found that senescent cells promote inflammation, which disrupts normal tissue functions and drives the progression of cancer. The lab’s pioneering discoveries are shedding light on anti-cancer genes, DNA repair mechanisms that promote longevity, molecular pathways that protect cells against stress, and stem cells and their role in aging and age-related disease.

The Brand Lab is studying mitochondria, which extract energy from nutrients and distribute it to drive the machinery of life in a process that also releases free radicals. Believed to be one of the primary actors in the aging

Dale Bredesen, MD Professor

Alzheimer’s Disease Dale Bredesen, MD, an internationally recog­ nized expert in the mechanisms of neurode­ generative diseases, came to the Buck Institute in 1998 as its founding president and CEO. His research has led to new insights that explain the erosion of memory seen in Alzheimer’s disease—insights that are opening the door to a new therapeutic approach.

Campisi is internationally recognized for her contributions to understanding why age is the largest single risk factor for developing cancer.

An elected Fellow of the American Association for the Advancement of Science, she has received numerous awards, most recently, the Longevity Prize from the IPSEN Foundation.

Dr. Bredesen has found that Alzheimer’s disease stems from an imbalance in nerve cell signaling—a finding that contradicts the belief that Alzheimer’s is caused by the accumulation of sticky plaques in the brain. Several new thera­ peutic candidates based on his insights into the fundamental nature of Alzheimer’s disease are currently in pre-clinical trials, funded in part by a generous gift of $3.5 million from private philanthropist Douglas Rosenberg. process, free radicals are implicated in numer­ ous age-related diseases, including cancer, heart disease, stroke, and many neurological disorders.

Brand’s lab envisions treatments that would minimize the release of free radicals without inhibiting mitochondrial energy metabolism.

His lab is collaborating with other Buck labs to evaluate the role of the mitochondria in aging and in age-related diseases such as cancer, diabetes, Parkinson’s, Alzheimer’s, and Hun­ tington’s. This research has already opened up new potential drug targets for the control or treatment of these conditions.

Dr. Bredesen is also studying nerve cell signal­ ing in a collaboration between the Bredesen Lab and BioMarin Pharmaceuticals, Inc., which is seeking treatments for a rare form of Alzheimer’s disease—early onset Familial Alz­ heimer’s Disease (eFAD)—which can develop in people as young as 30 years of age.

Dr. Bredesen received his MD from Duke University Medical Center in Durham, North Carolina, and served as chief resident in neu­ rology at the University of California, San Francisco (UCSF), before joining Nobel laure­ ate Stanley Prusiner’s laboratory there as an NIH postdoctoral fellow. He has held faculty positions at UCSF; the University of California, Los Angeles; and the University of California, San Diego. He directed the Program on Aging at the Burnham Institute before joining the Buck Institute.

“Aging is controlled by genes and the environment and poses the largest single risk for developing a panoply of diseases. Why do organisms age, and why do these diseases rise exponentially with age? My laboratory aims to understand the molecular and cellular basis of aging in mammals.”

—Judith Campisi, PhD

Buck Institute 2012 Annual Report 37

Faculty Profiles

Lisa Ellerby, PhD

David Greenberg, MD, PhD

Associate Professor

Professor and Vice President for Special Research Programs

Huntington’s Disease: Stem Cells, Therapeutic Targets, and Treatments

Cerebrovascular Disease

Lisa Ellerby is an expert on cell death in Hunting­ton’s disease, an inherited disorder that attacks motor coordination and cognitive ability. The Ellerby Lab aims to understand the molecular mechanisms causing Huntington’s disease and to discover therapeutic targets and develop treatments for the disease.

Scientists in the Ellerby Lab recently corrected the genetic mutation responsible for Hunting­ ton’s disease using a human induced pluripo­ tent stem cell that came from a patient suffering from the disease. Neural stem cells generated

Bradford Gibson, PhD

Professor and Director of the Buck Institute Chemistry and Mass Spectrometry Core

Proteomics in Aging, Cancer, and Neurodegenerative Diseases Bradford Gibson established the Chemistry and Mass Spectrometry Core at the Buck Insti­ tute to support research into the molecular basis of aging and disease. His goal is to iden­ tify the critical biomolecules and the structural changes they undergo during normal aging that allow pathological processes to establish themselves.

from the corrected stem cells have been trans­ planted into a mouse model of Huntington’s and are now generating normal neurons.

Ellerby and Buck faculty Robert Hughes have discovered a new lead on potential drug thera­ pies for the disease. They discovered a gene mutation that produces an abnormal form of the huntingtin protein in a class of enzymes already implicated in stroke, cancer, and other disorders. Ellerby’s work suggests that inhibit­ ing this class of enzymes may lessen symptoms of Huntington’s disease and prevent nerve cell death. Further therapeutic targets were identi­ fied for Huntington’s disease that involve lipid metabolism enzymes.

Ellerby earned her PhD in chemistry from the University of California, Santa Cruz. She joined the Buck Institute in 2000. She was a senior research associate in neurodegenerative disease and apoptosis and a co-investigator with the Program on Aging at the Burnham Institute in La Jolla, California.

38 Buck Institute 2012 Annual Report

David Greenberg, MD, PhD, studies the innate responses that protect or repair the brain after a stroke. He hopes to uncover new treatments that can mimic and enhance these responses.

After a stroke, the brain responds by boosting the production of proteins that help cells to survive or tissues to regenerate. The Greenberg Lab is exploring the actions of two protective proteins—neuroglobin and VEGF, or vascular endothelial growth factor.

One of the most encouraging recent discov­ eries in neurobiology is the finding that new nerve cells can be born in the adult brains of mammals. Dr. Greenberg has shown that new neurons can arise as a response to stroke, and his lab has identified factors that promote this.

He is also working with Buck colleagues on cell transplantation as a therapy for stroke.

Dr. Greenberg is Vice President for Special Research Programs at the Buck Institute. After receiving his MD and PhD from the Johns Hopkins University School of Medicine, he

The Gibson Lab focuses on understanding the biological and chemical processes that are common to both age-related diseases and aging.

The lab’s scientists employ mass spectrometry, protein and carbohydrate chemistry, and struc­ tural biology techniques to track structural changes in aging cells and in age-­related dis­ eases such as diabetes, breast cancer, and Hun­ tington’s disease. The Gibson Lab is also part of a national consortium that is identifying early protein biomarkers of cancer in human plasma that may yield early diagnostic tests for specific cancers.

Gibson received his PhD in analytical chem­ istry from the Massachusetts Institute of Technology in 1983 and then took a postdoc­ toral fellowship in chemistry at Cambridge University in England. Before joining the Buck Institute in 2000, he was a professor at the Uni­ versity of California, San Francisco (UCSF), where he currently holds a joint appointment as Adjunct Professor of Chemistry and Phar­ maceutical Chemistry.

trained in internal medicine at New York ­Hospital–Cornell University Medical Center and in neurology at the University of Califor­ nia, San Francisco (UCSF). Before joining the Buck Institute in 1999, he was on the faculty of the Department of Neurology at UCSF and at the University of Pittsburgh.

Faculty Profiles

Robert Hughes, PhD

Henri Jasper, PhD

Molecular and Chemical Biology of Aging and Neurodegeneration

Enhancing Stem Cell Function to Promote Longevity

Robert Hughes explores the mechanisms of normal aging in healthy adults and in people with Huntington’s disease. His team in the Hughes Lab is searching for compounds that help preserve protein configurations in aging yeast cells, and investigating the systems that

Henri Jasper has made seminal discoveries about the effects of aging on stem cell behavior and the role of stress in regulating stem cell function. The Jasper Lab aims to discover how stress and aging influence the ability of stem cells to self-renew, and whether improving stem cell activity can influence the aging process in multicellular animals. Jasper’s team is expanding its research on stem cells and the process of regeneration in the intestines of fruit flies (Drosophila) to the tracheal stem cells of mice.

Assistant Professor

Professor

The Jasper Lab is also studying the networks that control metabolic homeostasis and influence lifespan. The lab’s scientists use the developing retinas of fruit flies to study stressinduced cell death and to identify molecular and cellular mechanisms governing tissue recovery after stress-induced damage to the genome.

maintain the ability of proteins to fold into the shapes that best support healthy functioning.

They aim to discover clues to similar functions in human cells.

Hughes has collaborated with Buck colleague Lisa Ellerby to find new molecular targets for potential drug therapies for Huntington’s disease, a progressive genetic disorder that destroys nerves, impairs movement, and causes cognitive decline. Hughes discovered that a set of enzymes implicated in stroke and cancer may also support the onset and progression of Huntington’s disease.

Hughes received his PhD in biology from Yale University. He completed postdoctoral fellow­ ships in biochemistry and genome sciences at the University of Washington in Seattle, where he worked in the laboratory of Stanley Fields, PhD, a pioneer in yeast technology. As an assistant professor in the Division of Medical Genetics at the University of Washington Medical School, Hughes developed yeast-based models of human genetic disorders. Before joining the Buck Institute in 2005, he was Director of Therapeutic Biology at Prolexys Pharmaceuticals in Salt Lake City, Utah.

Jasper received his PhD from the University of Heidelberg and the European Molecular Biology Laboratory. He became a research assistant professor at the University of Roch­ ester Medical Center in 2003, and an assistant professor of biology at the University of Rochester in 2005. In 2008, Jasper received a Senior Fellow Award of the Ellison Medical Foundation. He received a Glenn Foundation Award for Research in Biological Mechanisms of Aging in 2010. His research is supported by the American Federation for Aging Research, National Institute of Aging, National Eye Institute, National Institute of General Medical Sciences, New York Stem Cell Initiative, and Ellison Medical Foundation.

Pankaj Kapahi, PhD Associate Professor

Nutrition and Energy Metabolism in Lifespan and Disease Pankaj Kapahi’s research confirms the finding that diet plays a major role in aging, lifespan, and age-related diseases. Scientists in the Kapahi Lab explore molecular mechanisms in a search for strategies to extend healthy lifespan in people. Their research involves using 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 diet could lengthen the lives of fruit flies. The diet activated genes that lead to greater energy production in the cells’ powerhouse units, the mitochondria, and thus compensated for the cells’ age-related decline in performance.

Humans share the cellular mechanisms that link diet to longevity in fruit flies, and the benefits of dietary restriction are seen across all species. Kapahi was the first to demonstrate that the growth-signaling pathway called the TOR pathway, which is involved in cancer and diabetes, mediates the effects of dietary restriction.

Kapahi, who joined the Buck Institute in 2004, earned his PhD at the University of Manchester in England and completed post­ doctoral studies at the University of California, San Diego, and at the California Institute of Technology. He has received numerous honors and awards, including the Ellison Medical Foundation New Scholar award, the Eureka award from the NIH, and the Nathan Shock New Investigator Award from the American Geronotological Society.

Buck Institute 2012 Annual Report 39

Faculty Profiles

Brian Kennedy, PhD

President and Chief Executive Officer

Deepak Lamba, mbbs, PhD Assistant Professor

From Invertebrates to Mice to Extending Human Healthspan

Stem Cell Technologies for Age-Related Eye Disorders

Brian Kennedy’s innovative work in the biol­ ogy of aging began when he was a doctoral student at the Massachusetts Institute of Tech­ nology (MIT). Under the guidance of MIT Professor Leonard Guarente, he contributed to groundbreaking studies showing that a class of proteins called sirtuins influence aging.

He now studies the pathways that modulate

Deepak Lamba, a practicing physician from India, is one of the pioneers in the technology of making retinal cells from human embryonic stem cells and induced pluripotent stem cells in a laboratory dish. He has shown that retinal cells can be transplanted into the eyes of blind mice and rats and that after transplantation the treated eyes respond to light.

The Lamba Lab is researching new methods to treat macular degeneration, retinitis pigmen­ tosa, and glaucoma using stem cell technology.

Dr. Lamba’s lab is concentrating on the longterm efficacy and safety studies that are essen­ tial before this form of therapy can be offered to patients. Developing new approaches to creating patient-specific stem cells is another goal. Lab scientists can now reprogram skin cells into embryonic stem cells and then con­ vert them to retinal cells—a technology that will result in a better understanding of vision diseases and lead to new treatments and drugs to halt, prevent, or delay the onset of these diseases.

longevity in model organisms ranging from yeast to humans. A major focus of his current research is the target of rapamycin (TOR) pathway, which has been generating excite­ ment since it was shown that the drug rapa­ mycin can extend the lifespan and healthspan of mice.

Dr. Lamba earned his medical degree from the University of Mumbai, India, and practiced as

Determining whether pathways like TOR can be regulated to treat the diseases of aging is a goal of the Kennedy Lab, which focuses on cardiovascular disease and metabolic disorders like type 2 diabetes. Kennedy’s team also studies the genetic mutations underlying Hutchinson-­ Gilford Progeria Syndrome, a rare disorder that resembles premature aging.

Kennedy earned his PhD in biology at MIT and completed postdoctoral training at the Massachusetts General Hospital Cancer Cen­ ter in Charlestown, Massachusetts. He was an associate professor in the Department of Biochemistry at the University of Washington in Seattle when he was appointed President and CEO of the Buck Institute in 2010. He currently serves as co-editor-in-chief of Aging Cell, the most highly regarded journal in the aging field, and is a regular consultant in the pharmaceutical and biotech industries.

a physician there before moving to the United States, where he received his master’s degree in bioengineering from the University of Illinois, Chicago. He did his doctoral thesis and post­ doctoral work on generating and transplanting retinal cells derived from human embryonic stem cells and iPS cells at the University of Washington in Seattle.

Gordon Lithgow, PhD

Professor and Director of the Interdisciplinary Research Consortium on Geroscience

Molecular Mechanisms of Aging Gordon Lithgow’s work sheds light on the mech­ anisms of aging by identifying agents that extend lifespan or prevent age-related disease. Utilizing the microscopic nematode worm (Caenorhabditis elegans), scientists in the Lithgow Lab have discovered various factors that lengthen the lives of these animals, and they are applying these findings to studies on human cells.

Stress has emerged as a major factor in aging and disease, contributing to a breakdown in an organism’s ability to maintain optimal molecu­ lar stability. Maintenance of homeostasis in the face of stress is a common feature of increased longevity and healthspan. The Lithgow Lab has made seminal discoveries in the use of small drug-like molecules to promote homeostasis.

Lab members have found compounds that suppress the pathology associated with Alzhei­ mer’s disease. They are currently researching additional sets of compounds that extend lifespan and healthspan.

Lithgow received his PhD in genetics from the University of Glasgow, Scotland. Before joining the Buck Institute in 2001, he was a senior lecturer in molecular gerontology at the School of Biological Sciences at the University of Manchester in England. He directs the Buck Institute’s Interdisciplinary Research Consor­ tium on Geroscience.

“One theme continues to emerge from our work—that aging and disease stem from common mechanisms. Delaying disease by delaying the aging process is a serious proposition.”

—Gordon Lithgow, PhD

40 Buck Institute 2012 Annual Report

Faculty Profiles

Victoria Lunyak, PhD

Sean Mooney, PhD

Associate Professor

Associate Professor and Director of the Bioinformatics Core

Epigenetics and Human Adult Stem Cell Aging Victoria Lunyak is a leading scientist in epigenetics which explores how the genetic blueprint is read differently in different cells of the human body. Her work focuses on adult stem cells, which provide a continual supply of new cells to our tissues as they are needed.

The ability of stem cells to repopulate tissues declines with age, a finding that is emerging as a potential factor in the overall aging process.

The Lunyak Lab has been able to reverse the aging process of adult adipose stem cells in cell culture. Her research is aimed at discovering methods of improving stem cell function with age, which would enhance tissue maintenance, repair, and resistance to DNA damage.

The Lunyak Lab uses deep proteomic analysis, next-generation sequencing technology, and a variety of molecular biology approaches to identify the age-related epigenetic changes in human adult stem cells and understand their

effects on human aging. The lab has identified novel, previously unreported epigenetic modi­ fications in the chromatin of human adult stem and somatic cells that can serve as biomarkers of cellular and organismal aging.

Lunyak received a master’s degree in biophys­ ics from Leningrad Polytechnic Institute in Russia and earned her PhD in molecular biol­ ogy from the St. Petersburg Nuclear Physics Institute at the Russian Academy of Science in St. Petersburg, Russia. She did postdoctoral work at Brown University and at the Univer­ sity of California, San Diego (UCSD), before becoming an adjunct assistant professor in the Department of Medicine at UCSD. She joined the Buck Institute in 2008.

Computer Technology and the Next Generation of Biomedical Research

Simon Melov, PhD Associate Professor

Identifying Molecular Hallmarks of Aging Simon Melov, who heads the Institute’s Genomics Core, explores the role of the energy-­making units inside cells, the mito­ chondria, which produce a chemical fuel that powers the cell’s work but which also release damaging free radicals that are linked to dis­ ease. The Melov Lab studies proteins that help the mitochondria detoxify free radicals and tracks the decline of function in mitochondria that comes with age. Other research interests include the age-related bone disorder osteo­ porosis, age-­related heart disease, the role of methylation in the aging human genome, and development of molecular techniques to better understand single cell changes with age.

Sean Mooney develops and applies methods in computational biology and bioinformatics— the collection, storage, analysis, and dissemina­ tion of biological information—to predict and treat the molecular causes of genetic diseases.

As director of the Buck’s Bioinformatics Core, Mooney helps the Buck Institute’s 19 labs to capture, store, and analyze the deluge of data flowing from their work.

The Mooney Lab develops the computer algorithms and statistical models needed to manage, analyze, and generate hypotheses from the data the research generates. The lab is also refining methods that enable computers to form hypotheses about the underlying origins of genetic illness. The lab team has programmed computers to use statistics to predict which mutations in the DNA sequence will lead to significant malfunctions in humans and those which are probably not prime mov­ ers in disease. Such work could accelerate the discovery of diagnostic tests and therapies for inherited diseases.

Mooney, who joined the Buck Institute in 2009, received a PhD in pharmaceutical chem­ istry from the University of California, San Francisco. He was an American Cancer Society

In a landmark study, Melov and his collabo­ rators showed that the more vigorous pattern of gene expression found in young adults could be partially restored in older adults who followed a strength-training exercise program for 6 months. The Melov Lab looks for broader genetic fingerprints of aging by surveying the patterns of gene activity in various animals, including human beings, mice, and nematode worms (C. elegans).

Melov received his PhD in biochemistry from the University of London in England. He held positions at Emory University in Atlanta and at the University of Colorado in Boulder before joining the faculty of the Buck Institute as an associate professor in 1999.

John Peter Hoffman Fellow in the Depart­ ment of Genetics and Medical Informatics at Stanford University. He was subsequently appointed assistant professor in medical and molecular genetics at the Indiana University School of Medicine, where he co-directed the Bioinformatics Core.

Buck Institute 2012 Annual Report 41

Faculty Profiles

David Nicholls, PhD

Xianmin Zeng, PhD

Professor

Associate Professor

Mitochondrial Function and the Life and Death of Cells

Stem-Cell-Based Treatments for Parkinson’s Disease

David Nicholls established the Bioenergetics laboratory at the Buck Institute in 2000 before handing it over to Martin Brand in 2008. His research focuses on understanding how mito­ chondria act as the powerhouses of the cell— currently in relation to diabetes. He retains a part-time position at the Institute and spends 3 to 4 months a year here at the bench, where he continues to develop novel techniques to investigate in-situ mitochondrial bioenergetics.

For the rest of the year, he is based in Lund, Sweden, and travels extensively around the world lecturing and teaching.

Xianmin Zeng is working toward a treatment for Parkinson’s disease. The Zeng Lab focuses on studying neural development using human embryonic stem cells (hESCs) and human induced pluripotent stem cells (iPSCs) derived from adult cells, which can mimic the versa­ tility of hESCs. Zeng has developed methods to induce these stem cells to become the type of nerve cells that are degenerated and lost in people with Parkinson’s disease, and she has ensured that this process can be readily transferred to a Good Manufacturing Practice (GMP) manufacturing facility so that the products are qualified for clinical use.

Nicholls has researched mitochondrial func­ tion for more than 45 years and has almost 300 publications to his credit. Currently complet­

Arvind Ramanathan, PhD Assistant Professor

Molecular Physiology of Skeletal Muscle Regeneration, Cancer and Aging Arvind Ramanathan is taking an integrative approach to answering fundamental questions about cancer, aging, and skeletal muscle regeneration. He has been using metabol­ omics and chemical biology to understand gene–environment interactions—how envi­ ronmental signals regulate signals involved in aging and cancer. Ramanathan has identified metabolic signals that mediate mTOR signal­ ing and skeletal muscle differentiation.

ing the fourth edition (with Stuart Ferguson) of the standard textbook Bioenergetics, he is best known for his discovery of the original uncoupling protein, UCP1; for work on mito­ chondrial calcium transport and isolated nerve terminals; and for his research into mitochon­ drial dysfunction in nerve cells.

Nicholls received his PhD in biochemistry from the University of Bristol, England. He is a Fellow of the Royal Society of Edinburgh and holder of the 2008 Mitchell Memorial Medal from the European Bioenergetics Congress.

42 Buck Institute 2012 Annual Report

Using mass-spectrometric and imaging-based approaches, the Ramanathan Lab is seeking answers to some important questions. How does the environment regulate cellular phys­ iology? What are the molecular signals that integrate nutrients and organismal and cellular physiology with tissue regeneration? By what mechanisms does aging affect these molecular signals?

Ramanathan was born in Pondicherry, India.

He earned a doctorate in chemistry from New York University and completed his graduate work at New York University and the Univer­ sity of Wisconsin Biotechnology Center. His postdoctoral work was performed at Harvard University and the Chemical Biology Program at the Broad Institute of Harvard, and at the Massachusetts Institute of Technology as a research fellow. He joined the Buck Institute in 2011.

Zeng has also developed models for screening small molecules that can prevent or protect against dopaminergic neuron cell death. She has generated many iPSC lines both from patients with Parkinson’s disease and from control subjects. These cells and models will be useful for testing the potential of new drugs and for further pure research into the mecha­ nisms of Parkinson’s disease.

After earning a PhD in molecular biology at the Technical University of Denmark, Zeng did her postdoctoral training at the NIH. She joined the Buck Institute in 2005. She is a recipient of several major funding grants from the California Institute for Regenerative Medi­ cine, including a translational grant to develop clinical-grade dopaminergic neurons from pluripotent stem cells using a scalable process.

the 2012 Board of Trustees The Buck Institute receives support and guidance from a non-compensated Board of Trustees.

These recognized leaders from the business, science, and nonprofit communities set policy, approve financial plans, and help shape the strategic direction of the Institute.

Steven Burrill

M. Arthur Gensler Jr., FAIA

Fay Hartog Levin

Founder and CEO of Burrill & Company, a life sciences company involved in venture capital and merchant banking

Founder of Gensler, a global architecture, design, planning, and strategic consulting firm

Serves on the boards of the National Health Museum, the Kellogg Center for Biotechnology Management, and Catalyst Biosciences

Jim Gerber

Former Ambassador to the Netherlands, formerly a senior consultant at Res Publica Group, and Vice President for External Affairs at Chicago Field Museum

James Edgar

Co-founder of Western Athletic Clubs, Inc., the owner and operator of luxury athletic and health facilities throughout the West Coast

Chair of the Board of Trustees

Stephen Hauser, MD

Management consultant and founding member of Edgar, Dunn & Company, an international consulting firm

Chair, Department of Neurology, University of California, San Francisco

Former trustee of Rosenberg Foundation and San Francisco Library Foundation

Chair, Buck Institute Scientific Advisory Board

Harlan P. Kleiman

Russell H. Ellison, MD, MSC

Co-founder and CEO of Self Health Network

Executive Vice President of Paramount Biosciences, Inc.

Founder/CEO of Shoreline Pacific

Shahab Fatheazam

UCLA School of Theater, Film and Television board member

Managing Director and head of Healthcare, Lincoln International Formerly with GCA Savvian and Vector Securities International MA, Cambridge University; MBA, Columbia University

Co-founder of Long Wharf Theatre

Chair of the Buck Advisory Council

Charles La Follette President of La Follette Capital Former board member of Pacific Stock Exchange and Marin Community Investment Committee

Bill R. Poland Real estate developer, chairman and founder of Bay West Group in San Francisco

Edward A. “Ned” Powell Retired president and CEO of the USO World Headquarters

Barbara Morrison

Former Assistant Secretary of Management and Deputy Secretary at the U.S. Department of Veterans Affairs

President of TMC Development, a provider of real estate financing

E. Lewis Reid

Mayor of Belvedere, CA Founder and board president of Working Solutions, a nonprofit that helps micro-entrepreneurs access capital

Catherine H. Munson

Former chair of Buck Board of Trustees Director of Community Foundation, Sonoma County, California

Richard M. Rosenberg

President, LVPMarin Realtors

Chairman and CEO (retired) at Bank of America Corporation

Board member of the Marin Symphony Association

Larry E. Rosenberger

Chair of the board of Project Amigo in Cofradia, Mexico

Former President and CEO and current research fellow of Fair Isaac

Member of Frank Lloyd Wright Civic Center Conservancy

Co-author of The Deciding Factor: The Power of Analytics to Make Every Decision a Winner

Herbert H. Myers

MS in physics and ME from University of California, Berkeley

Regional Business Banking President of San Francisco Bay Region Wells Fargo & Company

David M. Perry

Mary C. Sauer Founder, Vice President, and Director of Sonic Solutions

Senior Managing Director of TeamCo Advisers

Scientific Advisory Board The Scientific Advisory Board consists of leading scientists in the fields of aging research and age-related diseases such as Alzheimer’s disease and cancer. Members of the SAB provide guidance on the Institute’s scientific and educational programs.

Stephen L. Hauser, MD

Steven A. Carr, PhD

Cynthia J. Kenyon, PhD

Chair, Buck Institute SAB

Director of Proteomics, Broad Institute of MIT and Harvard

Department of Biochemistry, University of California, San Francisco

Chair, Department of Neurology, University of California, San Francisco

Robert H. Brown Jr., MD, DPhil Professor and chairman, Department of Neurology, University of Massachusetts Medical School

Ana Maria Cuervo, MD, PhD Department of Developmental and Molecular Biology, Marion Bessin Liver Research Center, Albert Einstein College of Medicine

James L. Kirkland, MD, PhD Professor of aging research, Director of Mayo Clinic Robert and Arlene Kogod Center on Aging

Jeffrey D. Macklis, MD, DHST Director, MGH-HMS Center for Nervous System Repair, Harvard University

Thomas A. Rando, MD, PhD Director, Glenn Laboratories for the Biology of Aging; Professor, neurology and neurological sciences, Stanford University School of Medicine Deputy Director, Stanford Center on Longevity, Stanford University

Buck Institute 2012 Annual Report 43

Buck Advisory Council Chair of Buck Advisory Council Harlan Kleiman

Krikor Bezdikian Co-founder, Manco Los Angeles, CA

Trustee, Buck Institute for Research on Aging CEO, Self Health Network San Francisco, CA

Jeff Bohnson

BAC Members

Najib Canaan

Tarek AbuZayyad Partner, Head of Merchant Banking, Stanhope Capital LLP London, UK

Hussam Abu Issa Vice Chairman and COO, Salam International Qatar

Cinzia Akbaraly Founder, Akbaraly Foundation Honorary General Counsel of Italy in Madagascar Groupe SIPROMAD Madagascar

James A. Aleveras

CEO, AnswersMedia, Inc. Chicago, IL

Principal and Chief Investment Officer, Marinus Capital Advisors LLC Stamford, CT

Mehmet Celebi Partner, Illinois Office, Arti Bir Group, Founding Partner, Investments, Construction Naperville, IL

Mark Cutis Chief Investment Officer, Abu Dhabi Investment Council United Arab Emirates

Mazen S. Darwazeh Chairman of Board of Directors, Hikma Pharmaceuticals PLC Jordan

Investment Advisor Representative, J.P. Morgan Securities LLC San Francisco, CA

“Belonging to the Buck Advisory Council exposes me to a new space of research that will undoubtedly impact the world positively. It is a place where we can all make a difference.”

—Mehmet Celebi, Founding Partner, Arti Bir Group

Shahab Fatheazam

Veena Panjabi

Trustee, Buck Institute for Research on Aging Managing Director and Head of the Healthcare Group, Lincoln International LLC Chicago, IL

Vice President and Co-Owner, World Industries Miami, FL

Darla Totusek Flanagan General Partner, MKD Investments San Francisco, CA

Anthony Ghorayeb Chairman and CEO, G&G Capital Group Chicago, IL

James W. Harpel Senior Partner, Palm Beach Capital West Palm Beach, FL

Dato Fawziah Abdul Karim CEO, SSU Management Services Malaysia

Lady Jamileh Kharrazi Chairman, Jamileh Kharrazi Charitable Foundation United Kingdom

Ron Landes Founder and President, Landes Bioscience Austin, TX

Patte McDowell Wissam Ariss

James Edgar

Founder and Chairman of the Board, Star Goods Lebanon

Board Chair, Buck Institute for Research on Aging Founding Partner, Global Brand Positioning LLC Kentfield, CA

Mikhail Batin Executive Director, Science for Life Extension Foundation Moscow, Russia

David Elias Principal, Alesco Advisors East Amherst, NY

44 Buck Institute 2012 Annual Report

Founder and Board Chair, Cloud Nine Foundation San Francisco, CA

Catherine H. Munson Trustee, Buck Institute for Research on Aging President, Lucas Valley Properties Novato, CA

Thomas Peters President and CEO, Marin Community Foundation Novato, CA

Mary Poland Ross, CA

Douglas Rosenberg Kentfield, CA

Rashid Skaf President and CEO, AMX Corporation Richardson, TX

Delly Tamer Chief Executive Officer, Letstalk.com San Francisco, CA

Thomas D. Weldon Chairman and Managing Director, Accuitive Medical Ventures Fernandina, FL and Duluth, GA

David Wetherell Managing Partner, Burrill & Company San Francisco, CA

E. Packer Wilbur Chairman, Southport Properties Southport, CT

William E. Wolf CEO, BW Capital Partners Chicago, IL

the time has come for building upon a great foundation of charitable commitment and giving

T

Each of the 19 laboratories at the Buck focuses on a separate, compelling area of geroscience research. We are reaching out to connect that research to those for whom it matters most.

To accomplish our goals of growth, stability, recogni­ tion, and visibility, and to address the urgent need for basic biological research in aging and chronic disease, the Buck must broaden and deepen its sources of support.

The time has come to build upon the great generosity and commitment of our past and current donors and to realize the exciting promise of our mission to extend healthspan through research and education.

he community of donors to the Buck Insti­­tute expanded in 2011 to include the Buck Advisory Council; 10 new trustees; scores of new mem­ bers, corporate sponsors, and foundations; and a remarkable group of individuals who provided gifts to name the interior spaces at the Buck campus and chairs in the Drexler Auditorium. Last and certainly not least, there were those who included the Buck Institute as a beneficiary of their will or honored friends and loved ones with a testamentary gift in their name.

Together, this diverse group helped to ensure the sta­ bility of the Institute by providing crucial funds for operations, facilities, faculty recruitment, equipment, educational and public programs, building expansion, and new research.

Often misunderstood, the Buck’s financial picture includes a very important annual contribution from the founding Buck Trust. This contribution comes through the Marin Community Foundation, which also supports the Buck Institute for Education and Alcohol Justice, formerly known as the Marin Institute.

A fundamental part of the Buck Institute for Research on Aging, the Buck Trust accounted for 12% of our total income, or $5.7 million.

With a rapid decline in funding from the National Institutes of Health (NIH) brought on by stagnating budgets and the increased costs of the science the NIH does fund, the Buck Institute must look to indi­ vidual donors to bridge the gap. Individual donors understand and are inspired by the range of work, the innovation, and the collaboration that are part of the unique fabric of the Buck. While some are taken with the founding idea that aging and chronic diseases are linked in a causal relationship, others are drawn to the Buck by a personal interest in a particular disease.

In the year ahead and with the Buck’s new state-ofthe-art facility for the study of regenerative medicine completed, the fundraising priorities are clearly the recruitment of faculty, the acceleration of current research, and the funding of educational programs for children and adults. Each of these areas offers much promise for the Buck Institute to contribute to the field, increase knowledge, and deepen our connection to Marin County and the San Francisco Bay Area, where philanthropist Beryl Buck lived and dedicated herself to the well-being of others.

Buck Trust Income as Percentage of Total Revenue

Other Revenue

Buck Trust Allocation

82%

76%

78%

85%

88%

18%

24%

22%

15%

12%

FY2008

FY2009

FY2010

FY2011

FY2012

Buck Institute 2012 Annual Report 45

Financial StatementS Statement of Net Assets June 30, 2012 (With Summarized Comparative Information at June 30, 2011) 2012

2011

A s s ets Cash Grants and contributions receivable, net

$

Accounts and interest receivable Investments and investments held in trust

703,309 7,488,949

$

2,595,991 8,792,951

42,909

74,744

14,652,485

16,801,847

Notes receivable

477,752

246,393

Charitable remainder trusts receivable

817,422

799,091

Deposit and other assets

504,189

737,257

Bond issuance costs, net

1,099,695

1,141,726

108,693,786

86,854,073

$ 134,480,496

$ 118,044,073

$

$

Property and equipment, net

Total assets Li a bi lit i e s Accounts payable and accrued expenses Deferred revenue

4,752,829 4,892,500

Accrued interest payable

5,196,166 2,671,098

6,719

72,285

Notes payable

6,616,299

3,630,820

Bonds payable

80,600,000

80,600,000

96,868,347

92,170,369

33,249,612

22,723,410

4,268,417

3,055,904

94,120

94,390

37,612,149

25,873,704

$ 134,480,496

$ 118,044,073

Total liabilities Commitments and contingencies N et as s e t s Unrestricted Temporarily restricted Permanently restricted

Total net assets Total liabilities and net assets

Increases in Grant Revenue (in $millions)

$39.7

$40

$15.6

$35 $28.3

$30

$4.9

$25 $20

CIRM Infrastructure Revenue

$23.4

$21.4 $17.8

$15

$24.1

$18.9 Grant Revenue without CIRM

$10 $5 0

FY2008

46  Buck Institute 2012 Annual Report

FY2009

FY2010

FY2011

FY2012

Statement of Activities and Changes in Net Assets Year Ended June 30, 2012 (With Summarized Comparative Information for the Year Ended June 30, 2011)

Unrestricted

Temporarily Restricted

Total

Permanently Restricted

2012

2011

O pe rat i n g r eve n u e s, ga i n s, an d ot h e r s u p p or t Allocation from the Buck Trust

$

Grant revenues Contributions Interest and investment income

- $

-

39,659,898

5,689,335 $

-

-

$

39,659,898

5,689,335

$

28,298,550

5,764,910

1,591,820

2,002,117

-

3,593,937

3,013,044

55,998

-

-

55,998

78,753

Other income

244,538

-

-

244,538

129,516

Net assets released from restrictions

808,205

(808,205)

-

-

-

48,049,794

1,193,912

-

49,243,706

37,284,773

24,726,376

-

-

24,726,376

23,434,857

General and administrative

9,568,513

-

-

9,568,513

8,365,916

Fundraising

1,991,585

-

-

1,991,585

1,907,013

Bond interest and related costs

1,237,118

-

-

1,237,118

1,440,821

Total operating revenues, gains, and other support O p e rat i n g e x pe n s e s Research

Total operating expenses

37,523,592

-

-

37,523,592

35,148,607

Change in net assets from operations

10,526,202

1,193,912

-

11,720,114

2,136,166

N on-ope rat i n g activiti e s Change in value of split-interest agreements, net

-

18,601

(270)

18,331

129,436

-

18,601

(270)

18,331

129,436

10,526,202

1,212,513

(270)

11,738,445

2,265,602

22,723,410

3,055,904

94,390

25,873,704

23,608,102

94,120

$ 37,612,149

$ 25,873,704

Total non-operating activities Change in net assets N et as s ets

Beginning of year End of year

$ 33,249,612 $ 4,268,417 $

Operating and Capital Revenue for FY2012 Foundation and Other Grants 8%

Corporate Research Agreements 4%

Operating Expenses for FY2012 Fundraising 5%

Bond Interest and Related Costs 3%

Contributions 7% Interest and Other 1% Federal and State Government Grants 37%

Buck Trust 12%

General and Administrative 26%

Research 66%

CIRM Infrastructure Grant 31%

  Buck Institute 2012 Annual Report  47

Honor Roll of Donors The Buck Institute gratefully acknowledges the following donors for their generous contributions.

$1,000,000 +

Mazen Darwazeh*

$5,000–$9,999

Chad L. Barber

The S.D. Bechtel, Jr. Foundation

Helene and Russell Ellison §

Glenn Foundation for Medical Research

Darla Flanagan*

Deborah and Arthur Ablin Family Fund*

Carole Bennett and Norman Ciampi

Affymetrix, Inc.

Antoinette and Tom Benoit

Aida and Dale E. Bredesen

Rosemary and Bill Bergin

Gunnel and Larry Dingus*

BioSpherix, LTD.

Magaret E. Haas Fund*

Barbara and David Elias*

Jack Bissinger

Linda Hothem

Genentech, Inc.

Elaine and Lyman Black

Dato Fawziah Abdul Karim*

JK Capital Management, LLC

Kerry and Clark Blasdell

Brenda and Brian Kennedy

Marin Independent Journal

Will Block

Lady Jamileh Kharrazi*

Virginia M. Melvin and Ralph O’Rear

Rosalind and David S. Bloom

Ellen and Douglas Rosenberg Foundation Rowe Family Foundation*

$500,000–$999,999 Michaela and Jay Hoag Catherine H. Munson § *

James Harpel* Ambassador Fay Hartog-Levin § and Daniel E. Levin

$250,000–$499,999

The Konigsberg Family Trust

Gensler Family Foundation § *

Ellen and Charles S. La Follette § * Elisabeth R. Levy*

$100,000–$249,999

Lycera Corp.

Larry L. Hillblom Foundation

Mary McEachron

Mericos Foundation

Barbara H. Morrison §

Marylin P. Wanlass*

Susan Ohrenschall*

Patricia L. and John Cahill Jr.* Mary and Bill R. Poland § *

King and Bruce Sams Carrie Schwab-Pomerantz and Gary Pomerantz US Bank Judy C. Webb*

Laura and David Perry §

$50,000–$99,999

Gwen and Thomas Price

Diane L. and Edward A. Powell §*

Buck Institute Members $250–$4,999 A and P Moving, Inc.

Mary and Lew Reid § *

Beth and Joseph Aaron

Barbara C. and Richard M. Rosenberg §

Mohammed Abalkhail

Helen Bodington Nancy and N. Edward Boyce Ute and John Brandon Cecilia and Larry Bridges Ruth Broady Mary Jo and Henry J. Broderick Jean and Stuart Brown Diane and O. Davis Brown Anders Brunmark Barbara A. Buck Sally Buehler

$10,000–$49,999

Rosenberger Family Fund §

Jamal Abu Issa

Building and Construction Trades Council of Marin County

Hussam Abu Issa*

Sangamo Biosciences/Edward Lanphier*

Alfa Tech

Maria Cabreira-Hansen

Yaisa Andrews-Zwilling

Helen K. and John E. Cahill Fund

Patsy F. and R. Howard Annin Jr.

Jeanne J. Cahill

Joyce D. Applen

Cahill/Otto Construction JV

Wissam Issam Ariss*

Joan Capurro

Ruth L. and Anthony Arnold

Huguette Carleton-Lenz and Dieter Lenz

Tarek AbuZayyad* Cinzia and Ylias Akbaraly* James A. Aleveras Jr.* Mikhail Batin* Marjorie E. Belknap* Robert B. Buck Lynn M. and Najib S. Canaan* Cloud Nine Foundation* Joey and Warren C. Conklin Jess and A. Crawford Cooley* Mark N. Cutis*

Mary C. Sauer § and Robert Doris SENS Foundation Rashid Skaf * Elizabeth M. Stevens Liz Wallerstein* Thomas D. Weldon* David Wetherell* Winifred Johnson Clive Foundation William E. Wolf*

48 Buck Institute 2012 Annual Report

Elizabeth and James Austin Barbara and Larry Babow Betsy Babson and Massoud Dehdashti Chris Balagtas Bank of Marin

Jeanne Carley Rosario Carr-Casanova and Richard E. Levy CaterMarin Wallace Chick

(§ Board of Trustees Member; *Buck Advisory Council Member)

Honor Roll of Donors Shankar J. Chinta

Francine Farouz

Rebecca and Robert Henn

Judy and Robert Leet

Carolyn S. Ciampi

Neghmeh and Shahab Fatheazam § *

Jessica Herritt

Mardi Leland

Patricia Hess

Sharon L. and Kenneth M. Levien

Marion and Jorgen Hildebrandt

John Levinsohn

Y. Anne Huang

Patricia and Lyle E. Lewis

Deborah Huber

Linda Liscom Janis R. MacKenzie and Dennis Conaghan

Carter Cliff Codding Foundation Toast and George Coley

Marjorie Feder Carmen M. and Ronald Ferguson

Jackie W. Collins

The Florence S. Mahoney Foundation

Karen Collins

Judi and Fredric Finkelstein

Judy Hunt

Patricia Conway and James L. Patten

Isabelle and Denis Finney

Lander R. and William Hynes

Adrian Flierl

Ann and Joseph Imhoff

Helen Fong

Gabriella and Glenn Isaacson

Frank Howard Allen & Co.

ISEC

Barbara and E.W. Fredell

Barbel and Gordon Jacobs

Friends of Marin Hadassah

Helene and Stephen N. Jaffe

Dolores Fruiht

Arnie J. Kahn

Pamela A. Cook and Paul Gietzel M. Aline Cornelius and Alan Estes Corning Life Science Stone Coxhead Judith D. and Robert K. Creasy Katherine Culligan Arleen Curry Shahla Davoudi Dibble & Dibble Noel W. and Donald R. Dickey Christine Dohrmann Marjorie and Jeron Donalds S. Malvern Dorinson

John D. Furber Betty E. Gandel

Francine and John R. Manis Nancy E. Martin Robert Mathison Marlyn and Larry McClaskey Shirley B. McDonald Catherine D. McKown

Peggy and Robert Fujimoto Alison Fuller

Delphine and Dennis Mangan

“I feel privileged to occupy a front-row seat on cutting-edge science.”

— Vernon Dwelly, Buck Institute docent and donor

Elizabeth and David Ganz The Geistlinger Family Trust Gary Giacomini

Denise Kalos

James W. Meakin

Roseanne and Raja Kamal

Deborah and Al Meckler

GlobalStem

Aileen A. and Daniel F. Keegan

Jane Miller

Joanne Gordon

Janice and Bill Kerr

Raymond Moore

Nancy Gorsich

Norma King

Karen and William Morgenstern

Elizabeth and Joseph Greenberg

Mildred N. King

Carol Mowbray

Judy and James M. Edgar §

Frank and Barbro Greene Charitable Fund

Johanna Knoferle

Kari E. and Hans J. Mueller

Ginger and David Egan

Sara G. and Richard M. Griffith

Verna and Jack Krout

Lillian J. and Bernie F. Mulaskey

Delia F. Ehrlich

Peter L. Grossman

Nancy and Richard Kuhn

Lynn Jurich and Bradford Murray

Elaine Ellerton

Margie and David Guggenhime

Jacqueline and Carl Kuhn

Rita and Herbert H. Myers §

Audrey and Kenneth Ellingsen

Althina and Charles Halfmann

Elinor A. and James E. Lacy

Laurie Nardone

Maryann and John Elloway

Donna and James Halow

Ron Landes*

Jeanette F. Nichols

Elizabeth Enemark

Hilary and Chris Hansen

Mary J. Lang

E.M. Nomura

Lois B. Epstein

Ethlyn Ann Hansen

Almon E. Larsh Jr.

Jeremy Norman

Sally-Ann and Ervin Epstein

Gay D. and Wyman C. Harris

Ragnhild and Knut Larssen

Tom Novak

Jacqueline L. and Christian P. Erdman

Stephen L. Hauser §

Marsha and Michael Lasky

Frances K. and Louis D. O’Brien

Sumana Laye

On Point Productions, Inc.

Sarah Leach and Kenneth Drexler

The P&G Company

Sharon Leach

PAE Consulting Engineers

Catherine and Robert Doyle

Ruth Noah Giusto and Albert S. Giusto

Tedi Dunn and William H. Svabek Elke Neumann Dwelly and Vernon I. Dwelly Courtney Easley-Neal Dianne M. Easton

Phyllis M. Faber

Wanda R. Headrick and Hans Adler

Carolyn and Branwell Fanning

Kay Heigel

(§ Board of Trustees Member; *Buck Advisory Council Member)

Buck Institute 2012 Annual Report 49

Honor Roll of Donors Steve Page

Virginia and William Schultz

Trison Construction, Inc.

Under $250

Mandy and Samuel Parke

Mary Barbara Shultz

Turck, Inc.

AA Electric SE Inc.

Barbara Patton

Jackson Scott

UnionBank

Judy and Paul Archambeau

Lynn and Richard A. Payne

Michele E. Scott

Charlotte S. and Donald F. Urban

Linda D. and Ted N. Baker

Gail Perin

Nancy and Robert Sellers

Ron Viner

Lois Ball

Grace and Roland Perkins

Christopher S. Semler

Aaron Vollrath

Susan T. Ballinger

Steven Perlmutter

Susan Severin

Lorraine and Vartan Voskanian

Kenneth Bauman

Donna and Jerry Peters

Shamrock Materials, Inc.

Mr. and Mrs. J.D. Warren

Neil Bauman

Constance Peterson

Brenda Shank

Evelyn Warren

Shirlyn and David Bauman

Ken Petron

Ingrid Sheets

Martha A. and Douglas A. Watt

Patricia and Donn Bearden

Virginia and Don Pierce

Colleen and John Silcox

Ann and Mark Weinstock

Marie Cressey Belden

Kelley Baer and Louis R. Pozzo

Sybil Skinner

Susan Wheeler

Randi and Robert Belshe

Melissa Prandi

Don and Jean Smith

Ellen White and Ronald F. Gaines

Marjorie L. Bertolino

Lois Prentice

Jenifer and John Smyth

Kay C. and Rick White

Josephine and George Blagden

ProMab Biotechnologies, Inc.

Helmut Sommer

Svetlana and Tommie Whitener

Janet A. Blasi Hayssen

Janet and Rudy C. Ramirez

Cherie and Gideon Sorokin

Peggy and Charles Wilson

Mark Brandt

Phyllis and Steven Reinstein

Donna and David Spilman

Shannon Wilson and Janine Guillot

Helen V. and Frederic L. Brenlin

Joan Ring

Rodney Stock

Pat and John Withers

Barbara C. Carter

Karen Ring

Ed Stolman

Judy V. and Donald E. Wolf

Chi-Hui Chai

Carma Rose

Vi and Dick Strain

Gerold C. Wunderlich

Richard Chan Elaine and Ken Chew

“My late husband, S. William Levy, MD, was a consultant to the Buck Institute since its inception. He immediately recognized the importance of such a research facility.

Now we, the family, carry on his legacy and give continued support to this important endeavor.”

—Elisabeth Levy

Patricia and Melford Chudacoff Janet and Stanley Clark Nancy Coit Carolyn Collins Anne Corwin Cosmos Cotati Terminal

Linda Rosen

Dawna and J. Dietrich Stroeh

Gloria and Peter Yu

Janice and Richard Cotton

Rutherford & Chekene

Pauline L. and John G. Stuber

Merla Zellerbach and Lee Munson

Robert B. Crankshaw

Renee Rymer and Tony Clementino

Sunrun

Careen Zelli and Joseph Antoun

Cross Stitch Cupboard

Samer Salty

Irving and Marilyn Tallman

Virginia Cunningham

Nancy Marsh Sangster-De Haan and Robert De Haan

Tony Tamer

Janet Daveiro

Beverly Tanner

Nancy L. and Raul G. Diez

Nancy Thomson

Amy Flannigan Dittmer

Roxanne Thornton

Diane Dorfman

Three Swallows Foundation

Jean and Kevin Dowling

Sally Tilbury

Carrie A. Driscoll

Berit Tisell

Charles A. Dunkel

Ruthellen Toole

Ann Eckelhoff

Reva Saper Betsy and John Scarborough Hermann E. Schnabel Gail Schroeder Birgitt Schuele Andrea Schultz

50 Buck Institute 2012 Annual Report

(§ Board of Trustees Member; *Buck Advisory Council Member)

Honor Roll of Donors Eckhoff Accountancy Corporation

Mary M. and John R. Hofmann Jr.

Phyllis and John Mueller

Charmaine Eng-Ngin

Helyse Hollander

Scott Nelson

Letty and Orville Erringer

Lillian B. Jarvis

Karla Noyola

A.S. Erwin

Betty and Gene Jemail

Ann W. Ocheltree

Kathleen and Dick Eschleman

Ruth Kagan

Opperman & Son

Kristi Evans

Joyce Kami

Betty H. Palkowski

Kit Everts

KB Electronics

Claire A. Pass

Molly A. Susag and Edward A. Walker Watcharin Tararattanakorn Eva Teller Sandra M. Teller Michael A. Thompson Sally Tilbury Donald N. Tornberg

“I have had the privilege of supporting the Buck Institute from its modest beginnings. With outstanding leadership and planned expansion, it has become not only a nationally recognized research organization, but a unique resource and treasure to those of us who live in Marin County.”

—Marjorie E. Belknap, MD

George L. Fernbacher

Rae and Robert B. Keating

Angelo Pastorino

Don Ferrell

Diana and Milt Kelly

Peter Pelham

Elizabeth and Robert Finer

Claire and John P. Killeen

Neil B. Peterson

Poppy H. Finston

Marion and William Kleinecke

Nancy and Robert Praetzel

Graham Forder

Leslie Ann and William Thomas Knapp

Boyd Quinn

Helen and Jacob J. Foster Sally J. and Thomas A. Freed Madelon and Roger R. Fross Clara Pearl Fusco Solange and Andre Gabany Gail S. and Marc Goldyne Patricia and Joseph A. Gryson Ilse Gudehus Evelyn and Leo Gurevitch Douglas Hamilton BJ and Steve Hansen Glenne Harding Anita M. and William Dennis Hassler

Betty Ann Kniesche Barbara Kraus K. and G. Krone Maria Kuester Alexander Kwan Anna and Martin Lackner Helen L. LaHaye Mary J. Lang Pamela and John Larson Brian Lepsis Ellen and Victor Levin Beverly Z. and Myron J. Levy Jane Luckoff

Elizabeth and Jack R. Heinz

Julia R. Marquette

Helen A. Heitkamp

Ed McCooey

Helen Hennessy

Johanna McMichael

Gloria and Donald Herzog

Joanne and Bob Millum

Ann L. Heurlin

Dona Moberly and John P. Taylor

Barbara Hoffman

Katherine B. Mohr

Judy Tsou and David Carlson Ewa Uding Beverlie M. Vandre Marjorie Walter Joyce B. Wells Phyllis and L. Warren Welsh Gloria D. Wilson and Edward Dermott Susan and Ian R. Wilson Patricia Wong and Ronald E. Lok Vera M. Young

Vida Ray and Ted Freeman Red Lion Controls Carol Ross Yvonne Roth Moe Rubinstein Lois Model Rukeyser Dixie J. Ruud Deborah and Paul Sagues Joan M. Shannon Mary Richards Yort Shattuck Fumio Shibata Lydia B. and Charles A. Sloan Smith Ranch Homes Phyllis and Peter Sommer Geoffrey Spellberg Kathy and Bob Steinbaugh Sucherman Consulting Group, Inc. Douglas W. Sullivan Shirley A. Sullivan

(§ Board of Trustees Member; *Buck Advisory Council Member)

Buck Institute 2012 Annual Report 51

Buck Staff B r ian K e nn e dy , P h D President & Chief Executive Officer

N ancy D e r r Vice President, Finance & Chief Financial Officer

Rowena Abulencia Emmeline Academia Pooja Agrawal Kazutaka Akagi Silvestre Alavez Alexander Alleavitch Mahru An Julie Andersen Suzanne Angeli Arieanna Anies Joseph Antoun Robert Archuleta Nathaniel Areceneaux Deepthi Ashok Audrisz Asuncion Tracy Barhydt Ricardo Barrera Lakisha Barrett Leslie Belingheri Christopher Benz Dipa Bhaumik Adrian Bivol

As of June 30, 2012

M ary M c E ach ron ,

R aja K amal , P h D Senior Vice President for Institute Relations

JD Chief Administrative Officer & General Counsel

K r i ste n G ate s , E d D Director, Postgraduate Education

R e my G ross III Vice President, Business Development & Technology Advancement

D e n i s e K alos Vice President, Wellness Programs

K evi n K e nn e dy

R alph O’R ear

B lai r W i nn

Director, Information Technology

Vice President, Facilities & Planning

Director, Resource Development

Benjamin Blackwell Akilah Bonner Martin Brand Dale Bredesen Regina Brunauer Libbie Butler Francis Byrnes Gabriellee Cailing Timothy Camarella Judith Campisi Bernadette Castro Lise Castro Greg Ceniceroz Di Chen Shankar Chinta Brent Clegg Cindee Crawley Julie Creighton Danielle Crippen-Harmon Evelyn Crivello Steven Danielson Albert Davalos

Staff Origins map

52 Buck Institute 2012 Annual Report

Darcy Davis Sonnet Davis Francesco De Giacomo Marco Demaria Olivier Descamps Seana Doughty Guiping Du Carlotta Duncan Lisa Ellerby Shiena Enerio Richard Fay James Flynn Juliette Gafni Abirami Ganesan Thelma Garcia Brittany Garrett Theo Garrett Akos Gerencser Bradford Gibson Olivia Gorostiza Jill Graham David Greenberg

Robert Guempel Lisa Gurney Bachir Hadid Jeong-Hoon Hahm Chong He Karen Hein Jason Held Dillon Hench Justin Hill Victoria Hogue Jennifer Holcomb Lynnette Hollins Katherine Hughes Robert Hughes Henri Jasper Shelly Jennings Lori Jensen Varghese John Darci Kane Pankaj Kapahi Subhash Katewa Shana Katzman

Desmond Kelly Amit Khanna Bo Khanrasa Demetris Killian Yong-Hwan Kim Janet King Ida Klang Marysia Kolipinski Jennika Krisa Jeff Kroyer Jitendra Kumar Remi-Martin Laberge Deepak Lamba Joann Lassak Matthew Laye Judith Lewis Jay Lewis-Kraitsik Biao Li Wai Li Chen-Yu Liao Christopher Lieu Chandani Limbad Gordon Lithgow Qiuyue Liu Su Liu Daniel Lockshon Vicky Loel Renee Lontz Tamara Loomis Allison Lorenzi Mark Lucanic Victoria Lunyak Gregory MacIntosh Alex Madias Julie Mangada

Jonathan Manning Xiao Mao Karla Mark Alex Matalis Richard Maxwell Thomas McBride Mark McCormick Cary McDonald Linda McDougal Matthew McGee Marie McKinney Simon Melov Eduardo Meza Jackson Miller Kylie Mitchell Olga Momcilovic Judith Montoya Justine Montoya-Sack Shona Mookerjee Sean Mooney Anne Neill Ryan Ng David Nicholls Robert O’Brien Shannon O’Hare Monique O’Leary Michelle Ohlson Adam Orr Lisa Palma Dorina Papanikolaou Kyungchae Park Alexander Patent Oliver Pedersen Ophelia Pedersen Jun Peng

Buck Staff

Design: 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

Juniper Pennypacker Irina Perevoshchikova Theodore Peters Clare Peters-Libeu Christopher Place Robert Place Todd Plummer Chris Pobre Jordan Poinsett Karen Poksay Deborah Post Milena Price Casey Quinlan Subramanian Rajagopalan Arvind Ramanathan Anand Rane Padma Rao

Rammohan Rao Matthew Rardin Maryanne Ravano Kris Rebillot John Reeder Lorri Reinders Brandon Reitzel Joseph Reynolds Armelle Richard Ilan Riess Christine Robbins Jennifer Rodrigues Aric Rogers Tal Ronnen Oron Daniel Rothschild Alex Sabogal Richard Safreno

Melissa Sarantos Birgit Schilling Gary Scott Chester Seligman Atossa Shaltouki Tong Shi Masha Shifs Almas Siddiqui Mara Sinats Joanna Sitzmann Renuka Sivapatham Dylan Sorensen Patricia Spilman Steve Spusta Tara Srinivasan Tom Starr Joel Sunga

Molly Susag Anna Swistowska Brandon Tavshanjian Veena Theendakara Jonathan Thompson Janita Thusberg Marc Ting James Tollervey Cendrine Tourette Shih Yin Tsai Mitsuhiro Tsuchiya Scott Tsuchiyama Stelios Tzannis Joanne Van KampenJohnsen Miguel Vargas Michael Velarde

Andrew Vinson Catherine Vitelli Alicia Wallace Darrain Waters Adrianne Williamson Joy Wilson Kathleen Wilson-Edell Justin Winstead Tobias Wittkop Sun Won Kim Lin Xie Bridget Yates Hoi Sze Yau Mariya Yevtushenko Khan Zafar Chris Zambataro Xianmin Zeng

Ningzhe Zhang Qiang Zhang Yiqiang Zhao Ying Zou Artem Zykovich

Buck Institute 8001 Redwood Blvd.

Novato, CA 94945 Tel: 415-209-2000 Fax: 415-899-1810 E-mail: info@buckinstitute.org www.buckinstitute.org