The document discusses the Buck Institute's growing global partnerships and business development efforts to advance aging research. Due to discoveries made by Buck scientists and a decline in NIH funding, business development became a top priority. The Buck has established partnerships across the globe in countries like Brazil, Russia, Japan, and China to pursue joint research, licensing agreements, and investments. These partnerships will help accelerate translating research findings into new therapies to extend healthspan worldwide. The Buck has also hired experts in business development and is exploring opportunities in health policy to have a greater impact on global health as a leader in aging science.
2. Age-related disease is
arguably the single greatest
challenge for biomedicine in
the 21st century.
3. And for governments around the world, the
greatest challenge may be the tidal wave
of health and economic impacts caused by
rapidly aging populations.
4. 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.
5. The time has come for the
Buck Institute to fulfill its
founding promise to increase
healthspan—the healthy years
of human life.
7. 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
Buck Institute 2012 Annual Report 5
8. the buck index 2012
Number of people worldwide who will be age 65 and older by 2030: 1 in 81
Growth rate of older populations in developed countries between 2010 and 2050: 71%
growth rate in less developed countries: 250%2
Percentage of older Americans living with one chronic condition: 80%
percentage living with at least two: 50%3
Portion of United States’ health care costs used to treat chronic diseases: two-thirds4
Percentage of older Americans’ health care costs spent to treat chronic diseases: 95%5
Percentage that the lifespan of healthy nematode worms is extended when exposed to Thioflavin T,
a common laboratory dye: 50%6
Rank of the United States of per capita health expenditures in the world: 17
Chance that an American age 65 or older has Alzheimer’s: 1 in 88
Expected increase in Alzheimer’s disease costs in the United States between 2011 and 2050:
$183 billion to $1.1 trillion9
Percentage that weekly moderate exercise reduces the risk of developing breast and colon cancers: 21–25%10
Chance that a woman in a high-income country is sufficiently active: 1 in 211
Percentage of Americans age 65 and older who did not exercise in the past month: nearly 32%12
Percentage of all American cancer cases diagnosed in people age 55 and older: 77%13
1 National Institute on Aging. “Overview: Our Aging World.” Why Population Aging Matters: A
Global Perspective.
2 National Institute on Aging. “Humanity’s Aging.” Global Health and Aging.
3, 19 National Center for Chronic Disease Prevention and Health Promotion, Division of 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 Alavez, Silvestre, et al., “Amyloid-binding Compounds Maintain Protein Homeostasis During
Ageing and Extend Lifespan.” Nature 472 (2011): 226–229.
7 World Health Organization. World Health Statistics 2012. (Geneva, Switzerland: World Health
Organization, 2012).
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).
6 Buck Institute 2012 Annual Report
9. the buck index 2012
Lifetime risk of developing cancer for an American man: 1 in 214
Lifetime risk of developing cancer for an American woman: 1 in 315
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: 15%17
Expected percentage of Americans living with cardiovascular disease in 2030: 41%18
Percentage of deaths caused by heart disease in Americans age 65 and older: 28%19
Frequency that an American dies from a coronary event: one every minute20
Number of deaths that could be prevented each year worldwide if salt consumption were reduced to recommended level:
2,500,00021
Percentage of the world’s adults who are overweight: 35%22
Percentage of Americans age 65 and older living with diabetes: 27%23
Percentage that engaging in weekly moderate physical activity reduces the risk of developing diabetes: 27%24
Percentage of the world’s blind people who are age 50 and older: 82%25
Percentage of visually impaired people who live in developing countries: more than 90%26
Percentage increase in the lifespan of nematode worms when treated with lithium: 46%27
Percentage that rapamycin extends lifespan in mice: 12%28
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.
23 Centers for Disease Control and Prevention. National Diabetes Fact Sheet: National Esti-mates
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 Caenor-habditis
Elegans.” Journal of Biological Chemistry 283 (2008): 350–357.
28 Harrison, David, et al., “Rapamycin Fed Late in Life Extends Lifespan in Genetically Hetero-geneous
Mice.” Nature 460 (2009): 392–395.
Buck Institute 2012 Annual Report 7
10. A stunning percentage of the world’s population
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 populations,
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 populations
among us, that money will be spent inefficiently
on treating individual diseases or building new hospitals
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, accelerate
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.
Through numerous new global initiatives and collaborations,
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-the-art
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 perspective
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 direction
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
President
8 Buck Institute 2012 Annual Report
11. It 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 creation
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 understanding
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 preventing
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, especially
during this period of restricted governmental
funding. Many of their accomplishments and expanding
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 million
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 program
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
Letter from the
Chair
Buck Institute 2012 Annual Report 9
12. the time has come for new business
networks and partnering
In 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 vigorous
and far-reaching approach to the creation of new
opportunities, collaborations, and partnerships with
academic institutions, corporations, and nonprofits
across the globe.
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. Productive
discussions ensued on early-stage investments
in promising research on the chronic diseases of aging,
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 fulfilling
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.
Going Global
“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
13. First Foray into Global Public Policy
In 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 possibility
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. Kennedy.
“With the work in our labs
and the expansion of our educational
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 System
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, Pharmaceutical
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 master’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 Advi-sory
Council (BAC) is a diverse
group of women and men from
around the world who are com-mitted
to supporting the mission
of the Buck Institute and serving
as its informal global ambassa-dors.
Council members include
leaders in venture capital, busi-ness,
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 inter-national
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 humani-tarian
awards to individuals who
demonstrate exceptional accom-plishment
and dedication in their
area of expertise.
Buck Institute 2012 Annual Report 11
14. Global Leader in Revolutionary Stem Cell Technology
One 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
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-stem-cell-
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, California.
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 parallel
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.
Going Global
Above: Fluorescent images of neural precursor cells
and dopaminergic neurons generated from human
embryonic stem cells.
12 Buck Institute 2012 Annual Report
15. Two years ago, the California
Institute for Regenerative Medicine
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 manufacturing
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 benefit
from the new stem cell therapy.
Zeng’s work is receiving international
attention. She has been globetrotting
“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.”
this past year to coordinate
stem cell manufacturing procedures
so that clinical trials can be
run in different countries, including
Japan, China, Argentina, and
Sweden. Argentina’s stem cell consortium,
which has an agreement
with the California Institute for
Regenerative Medicine, has asked
Zeng to serve on its scientific advisory
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 protocol
to use. My goal this past year
has been to show everyone that we
—Xianmin Zeng, PhD
Associate Professor
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 Parkinson’s
disease, to better understanding
of the mechanism of the
disease, and to testing new drugs
that may help Parkinson’s patients
in the future. “The global collaboration
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.”
Buck Institute 2012 Annual Report 13
16. 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.”
Partnering with Madagascar’s Akbaraly Foundation
In 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 economic
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 essentially
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-American
women. It lacks biomarkers
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-American
breast cancers, but nobody has
any data yet.”
Cinzia Akbaraly became a founding
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, cultural
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.”
—Cinzia Akbaraly
President, Akbaraly Foundation
14 Buck Institute 2012 Annual Report
17. Board Profile
Shahab Fatheazam
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 van-tage
point for appreci-ating
the role the Insti-tute
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 gov-ernment,
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 president,
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 fasci-nated
me.”
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.”
Below: Cinzia Akbaraly and Buck
faculty Dr. Chris Benz. Akbaraly
received the Humanitarian Award
at the 2012 meeting of the Buck
Advisory Council.
“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.”
—Christopher Benz, MD
Professor and Program Director
Buck Institute 2012 Annual Report 15
18. Year in Review
the time has come for realizing the
promise of regenerative medicine
New Era in
Stem Cell Research
In 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-of-the-
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
19. “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
20. Boosting the Regenerative Power of
Adult Stem Cells to Enhance Longevity
The Buck’s newest faculty member, Henri
Jasper,
PhD, brings an international reputation
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.
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.
Jasper, who received his PhD from the University of
Heidelberg in Germany and the European Molecular
Biology Laboratory, is focused on enhancing the function
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 regenerative
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 eliminate
cellular debris, including the wreckage associated
with aging. The funding will enable the Jasper Lab
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 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 has already begun collaborating with the Kennedy
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 signaling
on stem cell maintenance and regeneration.
Year in Review: new Faculty
18 Buck Institute 2012 Annual Report
21. “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
22. Year in Review: new Faculty
Innovating with Stem Cells to Treat Vision Disorders
For 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 Regenerative
Medicine Research Center.
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.
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-engineered
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
the eyes of mice. When Dr. Lamba tested the stem-cell-transplanted
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 transplanted
cells survive.”
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.”
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.”
20 Buck Institute 2012 Annual Report
23. above: Lamba Lab members are
(clockwise from left): Mark Gutierrez,
Deepak Lamba, Joe Reynolds, Ilan Riess,
and Thelma Garcia.
“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
Buck Institute 2012 Annual Report 21
24. Reversing the Aging Process
What 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.
In a landmark study undertaken with scientists from
the Georgia Institute of Technology, University of California,
San Diego (UCSD), Howard Hughes Medical
Institute, Memorial Sloan-Kettering Cancer Center,
International Computer Science Institute, Applied Biosystems,
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 transcripts
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 undifferentiated
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: New discovery
Below: Victoria
Lunyak, PhD,
Associate
Professor.
22 Buck Institute 2012 Annual Report
25. Training a New Generation of Scientists
More than a decade ago, Richard Klausner,
former Chairman of the National Committee
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 technology
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, productive
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 educational
programming to enhance the participation and
performance of the region’s youth in science and math.
The Buck hired its first full-time education coordinator
for K–12 as well as a director of postdoctoral education.
The Institute took the lead in coordinating local
activities for the Bay Area Science Festival, a weeklong
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-square-foot
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 community
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 dedication
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.
Pathways to priming the education pipeline
Attract
Invite children to
learn
The Buck’s
Education
Program
Retain
Choose to keep
learning
Persist
Lead students
to graduate
Attach
Continue to
STEM careers
Primary to
High School
Undergraduate
Education
Graduate
Education
Professorate/
Industry
Algebra Academy
Bay Area Science
Festival
High School Summer
Scholars
Undergraduate
Interns: 2- and 4-year
Graduate Students:
MS and PhD
Postdoc Trainees
Year in Review: education
Buck Institute 2012 Annual Report 23
26. Year in Review
Accomplishments
July 2011
The Providence
Journal
runs an op-ed
co-authored by
Buck faculty Julie
Andersen,
“Are We
Giving U.S. Infants
Too Much Iron?”
Proteome Sciences
and the Benz Lab to
develop biomarker
tests to improve
breast cancer treat-ment.
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 exper-imental
drug SRT-
1720.
On August 9, 2011,
the Buck Institute was
awarded a patent
titled “Small Mole-cules
that Replace
or Agonize p53
Function” (US Patent
# US7,994,184 B2).
P53 has been shown
to have the ability to
promote or retard
aging, depending on
the context of its reg-ulation
and activity.
The inventor is Dale
E. Bredesen, MD.
September 2011
Buck Institute and
Biotica collaboration
will evaluate rapa-mycin
analogs and
other polyketides
in a broad range of
age-related disease
models to identify
novel therapeutics.
Lunyak study in Cell
Cycle, “Scientists
Turn Back Clock
on Adult Stem Cell
Aging.”
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.
October 2011
The appointment of
Joseph Antoun, MD,
as Adjunct Faculty
marks the Buck Insti-tute’s
first foray into
public policy.
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.
Buck CEO Brian
Kennedy visits the
Middle East where he
explores partnerships
with pharmaceutical
companies, govern-ments,
and research
institutes.
The Arab Times and
Kuwait Times publish
op-eds by Buck CEO
Brian Kennedy on the
epidemic of type 2
diabetes now impact-ing
the Middle East.
November 2011
Buck Institute coor-dinates
North Bay
Discovery Day at
Infineon Raceway on
November 5. More
than 4,000 people
attend the signature
event during the Bay
Area Science Festival.
Buck faculty Judith
Campisi is quoted in
a New York Times
article focusing on
senescent cells and
aging.
December 2011
The Kleiman Multime-dia
Studio opens at
the Buck Institute.
Buck faculty Judith
Campisi and Simon
Melov are quoted in
a National Journal
article, “Longevity: A
Manual.”
James Edgar elected
as Chair of the Buck
Board of Trustees.
January 2012
The San Francisco
ABC affiliate runs a
story on the Buck’s
geothermal project.
Buck CEO Brian
Kennedy goes to
Tokyo and Singapore
to forge connections
between the Institute
and biotech and
pharmaceutical com-panies.
February 2012
Research from the
Melov Lab: A study in
Science Translational
Medicine shows mas-sage
reduces inflam-mation
and promotes
growth of new mito-chondria
following
strenuous exercise.
The story gets picked
up by several national
media—NPR,
Bloomberg, and USA
Today.
Buck CEO Brian
Kennedy
goes to
Central America to
set stage for scientific
collaborations that
would bring postdoc
fellows to Buck Insti-tute
labs.
The Costa Rica News
publishes an op-ed
by Brian K. Kennedy,
“A Wake-Up Call for
Costa Rica.”
March 2012
Buck Institute holds
Scientific Sympo-sium:
Stem Cells and
Aging.
Ambassador Fay
Hartog Levin and Lew
Reid join the Board of
Trustees.
Buck Institute
appears on Capitol
Hill; Buck CEO Brian
Kennedy helps launch
national “healthspan”
campaign.
April 2012
Henri Jasper, PhD,
hired as new faculty
member. Arrives in
the summer from
Rochester, NY, and
continues research
aimed at promoting
longevity by enhanc-ing
the activity of
adult stem cells.
USA Today runs a
story about the 100th
birthday of Buck
CEO Brian Kennedy’s
grandmother in
Louisville,
KY. The
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.
May 2012
The Greenberg Lab
publishes a study
in The Proceedings of
the National Academy
of Sciences focusing
on modifying scar
tissue following
chronic stroke.
The Buck Advisory
Council meets and
bestows awards for
scientific and human-itarian
achievement.
June 2012
The Glenn Foundation
awards $1 million to
establish training
fellowships in aging
research.
Steve Burrill and Jim
Gerber join the Buck
Board of Trustees.
The Ellerby Lab publishes
a study in Cell
Stem Cell—scientists
correct genetic muta-tion
responsible for
Huntington’s disease
in human induced
pluripotent stem
cells.
24 Buck Institute 2012 Annual Report
27. Buck Institute Publications by Year Board Profile
Catherine H. Munson
Motivation comes in all forms. Most people know
Catherine Munson as a Bay Area real estate pro-fessional
associated with the modern residential
housing developer
Joseph Eichler. But
an opportunity to
return to her scientific
roots prompted the
over-scheduled com-munity
activist to join
the Board of Trustees
of the Buck Institute
in 2004. Munson grad-uated
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 Insti-tute
is the most significant organization in Marin
County. Everyone ages—the Buck has a humani-tarian
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.”
Total 1,100
10
1999
41
2000
63
2001
78
2002
94
2003
85
2004
79
2005
102
2006
82
2007
75
2008
87
2009
98
2010
103
2011
103
2012
Buck Institute 2012 Annual Report 25
28. the time has come for bold science,
creative collaboration, and new therapies
Postdoc Collaborations—Heart and Soul
of Science at the Buck
At 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 scientists
can bounce ideas off each other and try novel
approaches to solving some of the fundamental problems
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 knowledge
and understanding of the biological processes of
aging. Their dedication and discoveries may eventually
lead to new therapies for some of aging’s worst maladies—
cancer, heart disease, and Parkinson’s.
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 projects
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.
POSTDOC COLLABORATIONS
26 Buck Institute 2012 Annual Report
31. Collaborating on a Parkinson’s Discovery
In 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 postdoctoral
fellow in the Kapahi Lab, which has an overall
focus on aging and nutrition.
Rogers is an expert in the biology of mRNA translation—
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. Siddiqui
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 possibility,
Siddiqui sought Rogers’s technical expertise.
Finding the answer was important because, as Rogers
explains, “Rapamycin, the drug used in Almas’s experiment,
targets a protein complex called TOR. This complex
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 combinations
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 neurodegenerative
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 trials.”
“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.”
left: In a conversation-fostering space, postdocs
Almas Siddiqui and Aric Rogers discuss their joint
research project.
above:
The central
dogma of
molecular
biology.
Buck Institute 2012 Annual Report 29
32. POSTDOC COLLABORATIONS
Exploring Rapamycin’s Effect on Heart and Bone Health
Postdoctoral 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 different
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 Washington
to study genes involved in aging and age-related
diseases in mice. In 2010 Kennedy, now the Buck Institute’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 translation,
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 downstream
of the actual molecule that’s called mTOR and
to understand how the mTOR signaling pathway relays
its signal throughout a cell or within an organism,” says
O’Leary. “From previous studies, we knew that rapamycin
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 rapamycin,
with an eye toward its potential use in humans.
We are hoping that our paper makes a significant
contribution to that body of work.”
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
33. Below: Postdocs Monique O’Leary and
James Flynn review data from mouse
studies involving the drug rapamycin.
Buck Institute 2012 Annual Report 31
34. POSTDOC COLLABORATIONS
Reducing the Inflammation
That Can Contribute to Cancer
Remi-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
35. Lab in 2010 after receiving a PhD in pathology from
the University of Rochester where she studied premature
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 rapamycin
to cells that he had forced to senesce by exposing
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 inflammation,
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 inflammatory
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 cancer
cells. Since the level of cytokines in blood is associated
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.”
This past year, Liu and Laberge tested over 200 different
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
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 surrounding
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 mechanisms
in different organisms, we can then apply them
to the various disease systems that others are researching
at the Buck.”
Buck Institute 2012 Annual Report 33
36. the time has come for geroscience—from
concept to reality to national participation
The Buck Institute is the birthplace of geroscience,
a new discipline focused at the intersection
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 disease.
One of the GSIG’s goals is to promote
the application of aging research
by developing public/private partnerships
with scientific societies, industry
groups, and other research institutes.
At the Buck, we see this growing interest
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 forefront,
keeping the momentum going.
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 bioenergetics,
stress biology, epigenetics, regenerative medicine,
neurodegeneration, molecular physiology, and bioinformatics—
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 member
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, collaborative,
and visionary—the Buck faculty are shedding new
light on aging and developing novel solutions to some
of its most daunting challenges.
Geroscience
AGE-RELATED DISEASE
Alzheimer’s
Cancer
Cardiovascular
Huntington’s
Macular Degeneration
Metabolic Syndrome
Osteoporosis
Parkinson’s
Progeria
Stroke
AGING STUDIES
Dietary Restriction
DNA Damage
Genetic Pathways
Mitochondrial Function
Oxidative Damage
Senesence
Translation
REGENERATIVE MEDICINE
Adult Stem Cells
Embryonic Stem Cells
Induced Pluripotent Stem Cells (iPSCs)
TECHNOLOGY
Bioinformatics
Genomics
Metabolomics
Morphology and Imaging
Proteomics
34 Buck Institute 2012 Annual Report
37. Geroscience Studies at the Buck
“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
NIH Record, August 17, 2012
Buck Institute 2012 Annual Report 35
38. Julie Andersen, PhD
Professor
Parkinson’s Disease
Julie Andersen is an expert on Parkinson’s
disease—an incurable, progressive neurodegenerative
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 proteins
that are involved in nerve cell degeneration
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.
Christopher Benz, MD
Professor and Program Director
Breast Cancer
Christopher Benz, MD, joined the Buck Institute
in 2000 as a founding faculty member. A
senior member of the UCSF Cancer Center’s
Breast Oncology Program, he set up the university’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 Analysis
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 personalized
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.
“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
Faculty
Profiles
36 Buck Institute 2012 Annual Report
39. Martin Brand, PhD
Professor
Energy Metabolism of Cells
Martin Brand is an authority on mitochondria—
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 University
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.
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
process, free radicals are implicated in numerous
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 Huntington’s.
This research has already opened up
new potential drug targets for the control or
treatment of these conditions.
Dale Bredesen, MD
Professor
Alzheimer’s Disease
Dale Bredesen, MD, an internationally recognized
expert in the mechanisms of neurodegenerative
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.
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 therapeutic
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.
Dr. Bredesen is also studying nerve cell signaling
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 Alzheimer’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 neurology
at the University of California, San
Francisco (UCSF), before joining Nobel laureate
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.
Judith Campisi, PhD
Professor
Cancer and Aging
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.
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.
“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
Faculty Profiles
Buck Institute 2012 Annual Report 37
40. Lisa Ellerby, PhD
Associate Professor
Huntington’s Disease: Stem Cells,
Therapeutic Targets, and Treatments
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 Huntington’s
disease using a human induced pluripotent
stem cell that came from a patient suffering
from the disease. Neural stem cells generated
from the corrected stem cells have been transplanted
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 therapies
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 inhibiting
this class of enzymes may lessen symptoms
of Huntington’s disease and prevent nerve cell
death. Further therapeutic targets were identified
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.
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 Institute
to support research into the molecular
basis of aging and disease. His goal is to identify
the critical biomolecules and the structural
changes they undergo during normal aging
that allow pathological processes to establish
themselves.
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 structural
biology techniques to track structural
changes in aging cells and in age-related
diseases
such as diabetes, breast cancer, and Huntington’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 chemistry
from the Massachusetts Institute of
Technology in 1983 and then took a postdoctoral
fellowship in chemistry at Cambridge
University in England. Before joining the Buck
Institute in 2000, he was a professor at the University
of California, San Francisco (UCSF),
where he currently holds a joint appointment
as Adjunct Professor of Chemistry and Pharmaceutical
Chemistry.
David Greenberg, MD, PhD
Professor and Vice President for
Special Research Programs
Cerebrovascular Disease
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 discoveries
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
trained in internal medicine at New York
Hospital–
Cornell University Medical Center
and in neurology at the University of California,
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
38 Buck Institute 2012 Annual Report
41. Robert Hughes, PhD
Assistant Professor
Molecular and Chemical Biology of
Aging and Neurodegeneration
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
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 fellowships
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.
Henri Jasper, PhD
Professor
Enhancing Stem Cell Function to
Promote Longevity
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.
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 stress-induced
cell death and to identify molecular
and cellular mechanisms governing tissue
recovery after stress-induced damage to the
genome.
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 Rochester
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 postdoctoral
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.
Faculty Profiles
Buck Institute 2012 Annual Report 39
42. Brian Kennedy, PhD
President and Chief Executive Officer
From Invertebrates to Mice to
Extending Human Healthspan
Brian Kennedy’s innovative work in the biology
of aging began when he was a doctoral
student at the Massachusetts Institute of Technology
(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
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 excitement
since it was shown that the drug rapamycin
can extend the lifespan and healthspan
of mice.
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 Center
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.
Deepak Lamba, mbbs, PhD
Assistant Professor
Stem Cell Technologies for
Age-Related Eye Disorders
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 pigmentosa,
and glaucoma using stem cell technology.
Dr. Lamba’s lab is concentrating on the long-term
efficacy and safety studies that are essential
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 convert
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.
Dr. Lamba earned his medical degree from the
University of Mumbai, India, and practiced as
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 postdoctoral
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 mechanisms
of aging by identifying agents that extend
lifespan or prevent age-related disease. Utilizing
the microscopic nematode worm (Caenorhab-ditis
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 molecular
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 Alzheimer’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 Consortium
on Geroscience.
Faculty Profiles
“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
43. Victoria Lunyak, PhD
Associate Professor
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 modifications
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 biophysics
from Leningrad Polytechnic Institute in
Russia and earned her PhD in molecular biology
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 University
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.
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 mitochondria,
which produce a chemical fuel that
powers the cell’s work but which also release
damaging free radicals that are linked to disease.
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 osteoporosis,
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.
In a landmark study, Melov and his collaborators
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.
Sean Mooney, PhD
Associate Professor and
Director of the Bioinformatics Core
Computer Technology and the Next
Generation of Biomedical Research
Sean Mooney develops and applies methods in
computational biology and bioinformatics—
the collection, storage, analysis, and dissemination
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 movers
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 chemistry
from the University of California, San
Francisco. He was an American Cancer Society
John Peter Hoffman Fellow in the Department
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.
Faculty Profiles
Buck Institute 2012 Annual Report 41