THE BURNHAM INSTITUTE
IN THIS ISSUE:
> Anti-obesity
> Genetic
drug inhibits prostate cancer growth
FROM RESEARCH,
research may improve heart function
> NIH-sponsored stem cell course held at Burnham
THE POWER TO CURE.
The Burnham Report SUMMER 2004
Vol. 2, No. 1
new treatments underway for prostate cancer. Potential
Prostate cancer growth can be slowed by a commonly prescribed anti-obesity drug, according to recent work by Burnham Associate Professor Jeffrey Smith and his research team. The investigators showed that the drug, orlistat (marketed by Roche as XENICAL™), inhibits prostate tumor growth in mice without any apparent side effects.
Welcome to the third issue of The Burnham Report. In this issue, you’ll read about the discovery that a commonly prescribed obesity drug may have efficacy against prostate cancer, a finding that opens the door to identifying new drugs with even more potency. You’ll learn about a growing research area at Burnham—investigations relevant to heart disease.Two of our newest faculty members round out our research team in this field. The issue of stem cell research is heating up, as Californians prepare to vote this fall on an initiative to provide state funds to support research not eligible for federal funds under current guidelines.The Burnham Institute has come forward in support of this initiative. Inside you’ll also read about our involvement in one of only five NIH-sponsored courses in human embryonic stem cell biology, held recently at Burnham and co-sponsored by Children’s Hospital Orange County. All of us at The Burnham Institute are grateful for your interest and support of our research.
“This is a big advance in the sense that
Additional screening of breast cancer
we have an approved drug—approved
and colon cancer cells revealed that
for one indication—that has another
fatty acid synthase activity is highly
target and another potential disease
active in these tumors as well, indicat-
indication, prostate cancer,” says Smith.
ing they may also be susceptible to
Tumor cells require enormous
orlistat or a similar drug. Orlistat was
amounts of energy to fuel their unbri-
originally developed to inhibit an
dled growth and division. Orlistat
enzyme that processes fats in the
works to cut off this energy supply by
digestive tract, thereby preventing
disabling an enzyme that plays a key
absorption of dietary fat.
role in metabolism, the production of
The screening method developed
energy from food. Smith and his col-
and used by Smith in this study repre-
leagues developed a chemical screen
sents a quantum leap in drug discovery.
that showed that prostate cancer cells
It allows investigators to compile
have unusually high levels of the
a comprehensive profile of a drug or
enzyme fatty acid synthase, which con-
potential drug’s activities, revealing
verts dietary carbohydrate to fat. The
unintended functions. Smith now
same screen also identified orlistat’s
plans to work on synthesis and testing
ability to block the enzyme. The results
of derivatives of orlistat to increase
were published in the March 15th edi-
the effectiveness of the drug’s action
tion of the journal Cancer Research.
toward tumors.
JOHN C. REED, M.D., PH.D.
President and CEO
Jeffrey Smith, Ph.D. Associate Professor, Cancer Center
The Burnham Report FROM RESEARCH,
THE POWER TO CURE.
THE DEL E. WEBB CENTER FOR NEUROSCIENCE AND AGING
“Young at heart”genes may mean longer lives. A diminutive mutant fly with the
humans, raising the possibility of
embryonic stem cells to become car-
colorful name of Tinman is telling
therapeutically improving the function
diac muscle cells (cardiomyocytes). For
investigators how the heart ages.
of an aging heart.
instance, a dish of cultured embryonic
These flies contain a mutation that
Bodmer and Oldham hope that drugs or genetic therapies can be devised, based on their work, that will help to delay or treat heart failure in humans.
New faculty members,
cells will form heart muscle cells that
causes them to have no heart and
A G E - R E S I S TA N T G E N E S
beat in unison, much like the rhyth-
were discovered by Rolf Bodmer, a
Like Bodmer, Assistant Professor Sean
mic beating displayed by a functioning
professor who joined The Burnham
Oldham makes use of the excellent
heart. Their work indicates that it
Institute in fall 2003. A gene like
genetics available for the fruit fly,
should be possible to develop protocols
Tinman was later found in humans as
scientifically known as Drosophila, to
to induce stem cells to differentiate
well, and mutations in this and many
examine biological pathways that
into functioning cardiac cells.
other “heart-forming” genes with
impinge on heart development and
relatives in flies are associated with
function. Oldham is studying mutants
embryonic stem cells can be cultured
congenital heart diseases. Bodmer
in a biological pathway that includes
in the same dish with genuine cardiac
also identified mutant flies that possess
a gene called Tor, which is known to
muscle cells, and in fact, some will
hearts that age more or less quickly
regulate many aspects of growth but
“pair up” with the more mature cells
than normal. That is, some elderly
had not previously been implicated in
and take on heart-like appearance and
flies about five weeks old possess a
heart function.
function. Problems develop, however.
heart equivalent of a young fly, and
Bodmer and Oldham hope that
Cardiomyocytes derived from
The cells appear normal for a time,
vice versa. These results suggest that
drugs or genetic therapies can be
but then undergo hypertrophy, similar
it may be possible to “uncouple”
devised, based on their work, that will
to the enlarged heart cells seen in
heart disease from the aging process
help to delay or treat heart failure in
people with heart failure. In collabora-
and prolong the condition of a heart
humans. They join a team of Burnham
tion with Assistant Professor Vincent
through later life. “Flies do not actually
investigators whose work is relevant to
Chen, Mercola’s group is examining
have hearts like we do,” says Bodmer,
understanding and treating heart dis-
how the stem cells in these cultures
“but they do have a small organ that
ease. Assistant Professor Giovanni
are communicating with their mature
pumps essential fluid, comparable to
Paternostro also uses the fruit fly as a
cardiomyocyte neighbors. Cardiac cells
blood, through their bodies.” As with
model. In flies, just as in humans, aged
are “electrically coupled,” exchanging
Tinman many of the “young at heart”
hearts do not withstand stress as well as
signals that allow them to beat in
genes he studies are also found in
younger hearts. Paternostro has found
harmony. Mercola and Chen hope
mutant flies whose hearts appear
to develop methods to normalize
perennially robust and is working to
electrical activity in differentiated stem
identify the molecular mechanisms that
cells. Mercola’s laboratory is also
cause this resistance to aging.
collaborating with a team of chemists
Rolf Bodmer, Ph.D., and Sean Oldham, Ph.D., discuss mutations that affect heart function.
to develop candidate drugs to combat C U LT I V A T I N G C A R D I A C C E L L S
the hypertrophy and induce more
Professor Mark Mercola has identified
stem cells to become heart muscle.
a number of genes that guide initial
“We really have a broad-based
formation of the heart in developing
effort now in heart disease research,”
embryos. His laboratory is now
says Mercola. “It’s very exciting to
applying this knowledge to induce
see it grow.”
NEWS AND NOTES
> Professor Stuart Lipton received the 2004 Ernst Jung Prize for Medicine in recognition of his “trailblazing research in the field of neuroscience and its diagnostic and therapeutic consequences.” In a May 2004 ceremony in Hamburg, Germany, Lipton received 125,000 (approximately $140,000) from
the Jung Foundation for Science and Research. German industrialist Ernst Jung endowed this award in 1976 to recognize outstanding scientific discoveries that have had a major impact in experimental medicine. The prize has been awarded to 56 scientists since its founding.
> Several large federal grants have been awarded recently to Burnham investigators working in the area of infectious diseases. Approximately $19 million in funding will support a multi-disciplinary team, headed by Professor Robert Liddington, in studies aimed at deciphering how virulence factors
cause cell death. Almost $10 million was awarded to support an effort, directed by Professor Alex Strongin, to design therapies for smallpox, and $1.5 million will fund a project, headed by Associate Professor Adam Godzik, to study the virus responsible for the emerging disease SARS.
BURNHAM
Burnham hosts an international workshop on stem cells. Satellite view
Participants spent a good deal of their
Thirteen graduate students, postdoc-
time working “hands on,” learning
toral fellows and technicians served as
methods for culturing stem cells, as
instructors for the laboratories, and all
well as analyzing them and transplanting
of the Burnham faculty in the stem
Scientists from around the world
cells into laboratory animals. Many
cell program participated in the course.
converged recently at The Burnham
scientists think stem cells have the
Almost all of the equipment and
Institute to attend one of only five
potential to replace cells lost to disease
supplies was donated by companies;
courses on human embryonic stem
in conditions such as Alzheimer’s,
Invitrogen and Chemicon provided
cell biology sponsored by the National
diabetes and heart disease.
chemicals, NuAire and Brinkman lent
Institutes of Health. The course,
“There is a long way to go, how-
equipment, and Corning and VWR
co-sponsored by Children’s Hospital
ever, until we can reliably prompt stem
supplied tissue culture materials.
of Orange County and Burnham, was
cells to turn into the type of special-
Olympus Instruments made nearly
held during two weeks in April and
ized cells we want for any particular
$100,000 worth of sophisticated
offered participants an opportunity to
purpose,” says Jeanne Frances Loring,
microscopes available.
immerse themselves in the field.
Ph.D., a Burnham adjunct associate
Students traveled from within the
professor and course co-director. “The
that this is an extremely important
United States, as well as South Korea,
techniques for growing these cells and
area and generously contributed to
Singapore and India.
encouraging them to thrive are still
the course’s success,” says Snyder.
“We were busy from about eight
being worked out. The purpose of this
“The scientific vendors believe
“We’re training the pioneers in
each morning until almost ten in the
course was to expose investigators to
this field,” adds Loring, “and expect
evening for ten days,” says Evan Snyder,
the best techniques available, so they
our first group of students to make
M.D., Ph.D., a Burnham professor and
can go back to their home institutions
their own important advances in
course co-director. “It was intensive.”
and share what they’ve learned.”
stem cell biology.”
THE BURNHAM REPORT JOHN C. REED, M.D., PH.D.
President and CEO KARIN EASTHAM
Executive Vice President and COO TERRY GACH
Vice President, Resource Programs SUZANNE CLANCY, PH.D
Editor, The Burnham Report LIPMAN HEARNE, INC.
Graphic Design BOB ROSS MARTIN MANN
Photography www.burnham.org
RESEARCH HIGHLIGHTS
Center Advisory Boards Further Research Mission. Investigators in The Burnham Institute’s two major research centers— the Del E. Webb Center for
Neuroscience and Aging Council of
CANCER CENTER
Advisors, Executive Committee.
ADVISORY BOARD
Both these groups are composed
For more information on the Cancer Center Advisory Board, please contact: Mr. Chris Lee, 858.713.9932, chrislee@burnham.org
Linden Blue Mary Beth Burnham Judge Robert Coates Dani Grady Charlie Jones Robert Kyle Helen Eckmann, Ph.D.
Neuroscience and Aging and the
of people who share an enthusiasm
National Cancer Institute-designated
for scientific research and a dedication
Center—conduct research leading to
to supporting the centers through
significant improvements in the treat-
their leadership roles in the community.
ment and prevention of disease, includ-
Members act as “ambassadors,” help-
ing many types of cancer, neurological
ing to raise public awareness of the
DEL E. WEBB CENTER FOR
conditions such as Alzheimer’s and
exciting work being conducted in the
N E UR O S C I E N C E S A N D A G I N G
other disorders associated with aging.
centers and stimulating greater com-
C O UN C I L O F A D V I S O R S ,
They are supported in this effort
munity involvement and philanthropic
by two special groups of friends—
support. The Burnham Institute is
the Cancer Center Advisory Board
very grateful for their support.
Nonprofit Organization U.S. Postage PAID The Burnham Institute
and the Del E. Webb Center for
For more information on the Del E. Webb Center for Neuroscience and Aging Council of Advisors, Executive Committee, please contact: Ms. Judy Cottrell, 858.713.9913, cottrell@burnham.org
EXECUTIVE COMMITTEE
Howard and Toby Cohen Bill and Susan Evans Lowell and Julie Potiker Bernie and Carey Simkin Bobbi and Bill Warren
The Burnham Report
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T H E B UR N H A M I N S T I T U T E
FROM RESEARCH,