winter 2009
DESCRIPTION
The year in translation Volume 6 | Number 4TRANSCRIPT
VOLUME 6 NUMBER 4 | WINTER 2009
From Research, The Power to Cure
InsIde >BURNhaM REsEaRch >PhIL aNThROPy
The Year in Translation
B U r n h a m R E P O R T
BL aIR BLUM Senior Vice President External Relations
ELIzaBETh GIaNINI Vice President External Relations
EdGaR GILLENWaTERs Vice President External Relations
chRIs LEE Vice President External Relations
aNdREa MOsER Vice President Communications
O N T h E c O V E R
It is the central tenet
of modern biology: The
information in our DNA
(right) is translated into
RNA (center), which
moves these coded
instructions from the
cellular nucleus and trans-
lates them into proteins
(upper left). In turn,
proteins are the machines that power virtually all aspects
of biology. Burnham scientists spend their careers studying
these interactions. Each year they learn more about how
cells function and what can go awry to cause disease.Burnham Institute for Medical Research10901 North Torrey Pines Road, La Jolla, CA 92037 • 858.646.3100
Burnham Institute for Medical Research at Lake Nona 6400 Sanger Road, Orlando, FL 32827 • 407.745.2000
Founders
WILLIaM h. F IshMaN, Ph.d. L ILLIaN FIshMaN
honorary Trustees
JOE LEWIs cONRad T. PREBys T. dENNy saNFORd
Trustees and Officers
GREG LUcIER Chairman
aL aN GLEIchER Vice Chairman
JOhN c. REEd, M.d. , Ph.d. President & Chief Executive Officer Professor and Donald Bren Presidential Chair
GaRy F. RaIsL, Ed.d. Executive Vice President Chief Administrative Officer Chief Financial OFficer Treasurer
MaRGaRET M. dUNBaR Secretary
Trustees
Mary BradleyBrigitte BrenArthur Brody
Trustees, continued
Malin BurnhamShehan Dissanayake, Ph.D.M. Wainwright Fishburn, Jr.Jeannie M. Fontana, M.D., Ph.D.David HaleJeanne Herberger, Ph.D.Brent JacobsJames E. Jardon II (Florida)Robert J. LauerFred Levine, M.D., Ph.D.Sheila B. LipinskyPapa Doug ManchesterRobert A. Mandell (Florida)Douglas H. ObenshainPeter PreussStuart TanzJan Tuttleman, Ph.D., MBAAndrew J. Viterbi, Ph.D.Kristiina Vuori, M.D., Ph.D.Bobbi WarrenAllen R. Weiss (Florida)Gayle E. WilsonDiane WinokurKenneth J. Woolcott
Ex-Officio
Raymond L. White, Ph.D.Chairman, Science Advisory Board
JOsh BaxT Editor, Burnham Report
GaVIN & GaVIN adVERTIsING Design
MaRk dasTRUPNadIa BOROWskI scOTTMELIssa JacOBsMaRTIN MaNNPhotography
Please address inquiries to: [email protected]
www.burnham.org
I N T h I s I s s U E
B U R N h a M R E s E a R c h
The Year in Translation 1
NCI-Designated Cancer Center 2
Del E. Webb Neuroscience, Aging and
Stem Cell Research Center 4
Infectious and Inflammatory Disease Center 6
Diabetes and Obesity Research Center 8
Sanford Children’s Health Research Center 10
Conrad Prebys Center for Chemical Genomics 11
UCSB-Burnham Center for Nanomedicine 12
P h I L a N T h R O P y
Meet Greg Lucier 14
The Power to Cure Gala 15
The Fishman Fund Awards 16
F I N a L T h O U G h T s
President’s Message 17
Partners in Science 18
The Year in Translation
Translation has a variety of definitions. It can mean translating one language into another. In scientific parlance, translation can describe how the information from our genetic code is converted into proteins. Also, translational research is the process by which basic scientific discoveries are moved from the laboratory to the clinic.
While these three defini-
tions describe very different
processes, they all apply
to the work being done at
Burnham. And 2009 was a
very good year for translation.
It is no secret that the
biological sciences have
a language all their own.
Complicated terminology is
often required to describe
complicated processes.
However, Burnham has
succeeded in making our
investigations more acces-
sible, and the world has
taken notice. In the past year,
Burnham science has been
described in the New York
Times, Wall Street Journal,
San Diego Union-Tribune and
Orlando Sentinel, as well as
on National Public Radio,
Fox Business News and many
other outlets. These stories
allow the world to see the
incredible work being done at
Burnham and help advance
scientific understanding.
In 2009, Burnham scien-
tists published more than
300 research papers, many
in high-profile journals. The
vast majority of these papers
illuminated some aspect
of translation. According
to Thompson Scientific, in
the past 10 years Burnham
research has received the
highest number of citations,
in biology and biochemistry,
of any institution publishing
more than 500 papers. In
other words, Burnham discov-
eries spark the creativity of
scientists around the world.
With the opening of
our new facility at Lake
Nona and a new Center
for Nanomedicine in Santa
Barbara, Burnham expands
both our basic and transla-
tional research capabilities.
New scientific and adminis-
trative leadership, as well as
multiple collaborations, will
advance the science and help
transform basic discoveries
into new medicines.
B U r n h a m d I a B E T E s R E s E a R c h
www.burnham.org | The BUrnham reporT 1
The Year in TranslationThe recently opened Conrad Prebys Center for Chemical Genomics facility at Lake Nona can conduct hundreds of thousands of assays to find chemical compounds that can alter protein function (see page 11).
B U r n h a m T h E y E a R I N T R a N s L a T I O N
2 The BUrnham reporT | www.burnham.org
BaTTLING METasTasIs
Metastasis is a word no one wants to hear. Cells that should
never leave their biological home migrate to distant parts of the
body. Many things have to go wrong with cellular checks and
balances for this to happen, yet it happens all too frequently.
To metastasize, cells must acquire a number of properties,
including the abilities to move,
survive in the bloodstream, cross
tissue boundaries and grow in
foreign organs. These last two
properties require the activity of
proteases, enzymatic proteins that
break down other proteins. Sara
A. Courtneidge, Ph.D., director
of the Tumor Microenvironment
Program, studies how the activity of
these proteases is controlled by cell
surface structures called invado-
podia. These finger-like projections
from the cell membrane are found
in metastatic cancer cells but not in
non-invasive cells. Dr. Courtneidge’s
laboratory discovered a protein,
called Tks5, which controls the formation of these invadopodia in
cancer cells.
Recently the Courtneidge laboratory showed, in an article
in Science Signaling, that reactive oxygens, such as superoxide
and hydrogen peroxide, play a key role in forming invadopodia.
Inhibiting reactive oxygen reduces invadopodia formation and
limits cancer cell invasion.
“Reactive oxygen has a complex cellular role,” says Dr.
Courtneidge. “Normal cells use reactive oxygen to signal, grow and
move. Immune cells, such as neutrophils, produce reactive oxygen
to destroy bacteria. Now we find that reactive oxygen is necessary
for invadopodia formation, which allows cancer cells to become
metastatic.”
ThE sEcRET WORLd OF PROTEINs
Ubiquitination is the process that marks proteins for destruc-
tion and is critical to cellular health. Recently, Dieter Wolf,
M.D., and colleagues, in an article in Molecular Cell, illuminated
how competition between proteins enhances diversity during
ubiquitination. Using S. pombe fission yeast as a model, the Wolf
laboratory uncovered an intricate relationship, in which an array of
proteins (called F-box proteins) alternately attach to and are kicked
off a protein called CRL1. There are 16 different types of F-box
proteins, and one of them must attach for CRL1 to fulfill its role of
marking a protein for destruction. If ubiquitination goes awry, aber-
rant proteins can accumulate and lead to diseases such as cancer.
Dr. Wolf ’s research shows that these proteins attach to CRL1
but are kicked off by the competing protein CAND1. F-box
proteins and CAND1 continue to trade places until they come in
contact with the appropriate part of the protein
being degraded.
“The tension between CAND1 and F-box
gives more F-box proteins the opportunity
to attach to CRL1,” says Dr. Wolf. “Without
CAND1, more prevalent F-box proteins would
dominate the process.”
Another way proteins communicate is
through enzymes called caspases (a type of
protease), which cleave, or nick, other proteins
to alter their function. Again, understanding
how this process works leads to a better under-
standing of how proteins collaborate and the
differences between healthy and diseased cells.
Using an advanced proteomic technique
called N-terminomics, Guy Salvesen, Ph.D.,
professor and director of the Apoptosis and
NCI-Designated Cancer Center
Dr. Sara A. Courtneidge
Invadopodia, seen as orange dots in this image, are found in metastatic cancer cells.
Cell Death Research
Program, graduate
student John Timmer
and others determined
the cleavage sites on
target proteins. Prior
to this study, published
in Nature Structural
and Molecular Biology,
scientists believed that
proteases primarily
cleave in unstructured
loops, unstable parts
of proteins that are
readily accessible. The
discovery that caspase-3
also cleaves α-helices contradicted that belief and offered new
insights into protein signaling pathways.
“This was a big surprise because there shouldn’t be anything
for a protease to grab onto in a helix,” says Dr. Salvesen. “We found
that the basic concept that they don’t cleave to helices is wrong.
However, though we’ve found that proteases can cleave helices, we
don’t believe that’s their biological function.”
Because they alter the functions of other proteins, proteases
like caspase-3 are critical to cell signaling. Understanding how
and where they interface with target proteins enhances our
ability to understand disease.
RENEWING ThE NcI -dEsIGNaTION
Every five years, Burnham’s Cancer Center competes for
renewal of its coveted NCI support grant. The process involves
a massive grant application, followed by a day-long site visit,
during which NCI sends experts to review the
Institute’s progress. This year, Burnham’s Cancer
Center received an overall rating of outstanding.
The NCI’s report noted:
“This center has many significant strengths in
terms of the quality of the basic science pursued
throughout its research programs and has made
noteworthy contributions to science that have
impacted cancer-related questions. Leadership
and planning and implementation mechanisms are
now in place to facilitate the synergy of its pool of
outstanding talent that can be directed at some of
the most fundamental processes driving the initia-
tion, growth and progression of cancer.”
B U r n h a m T h E y E a R I N T R a N s L a T I O N
www.burnham.org | The BUrnham reporT 3 www.burnham.org | The BUrnham reporT 3
Other Research HighlightskRIsTI INa VUORI, M.d. , Ph.d. , director of the
Burnham Cancer Center, and colleagues found that
Caspase-8, a protein long known to play a major role
in promoting programmed cell death (apoptosis), helps
relay signals that can cause cancer cells to proliferate,
migrate and invade surrounding tissues. For the first time,
Caspase-8 was shown to play a key role in relaying the
growth signals from the protein EGF that cause cell divi-
sion and invasion. Published in Cancer Research.
MINORU FUkUda, Ph.d. , and colleagues discovered
that specialized complex sugar molecules (glycans) that
anchor cells into place act as tumor suppressors in breast
and prostate cancers. These glycans play a critical role in cell
adhesion in normal cells, and their decrease or loss leads to
increased cell migration by invasive cancer cells. Published
in Proceedings of the National Academy of Sciences.
GaRy chIaNG, Ph.d. , and colleagues have
elucidated how the stability of the REDD1 protein is
regulated. The REDD1 protein is a critical inhibitor of the
mTOR signaling pathway, which controls cell growth and
proliferation. Published in EMBO Reports.
sTEFaN RIEdL, Ph.d. , and colleagues have deter-
mined the structure of the Fas/FADD protein complex
as the core component of the death inducing signaling
complex. This revealed a key mechanism in the induction
of programmed cell death and unraveled a novel mecha-
nism in receptor signaling. Published in Nature.
WEI J IaNG, Ph.d. , and colleagues have demon-
strated important new roles for the protein kinase complex
Cdc7/Dbf4 or Cdc7/Drf1 (Ddk) in
monitoring damage control during
DNA replication and reinitiating repli-
cation following DNA repair. Since
Ddk is often deregulated in human
cancers, this new understanding of its
role in DNA damage control could help
shape new cancer therapies. Published
in Molecular Cell.
Dr. Dieter Wolf
BURNHAM INSTITUTE for MEDICAL RESEARCH
Burnham recently published a report on our NCI-designated
Cancer Center. Progress on the Path to Cancer Cures is avail-
able by request. Contact Jane Langer at [email protected]
or 858-795-5288 to receive a copy.
B U r n h a m T h E y E a R I N T R a N s L a T I O N
4 The BUrnham reporT | www.burnham.org
The picture in the San Diego Union-Tribune showed a hand removing a sticker—a small action with deep significance. The sticker, and others like it, described federal restrictions on stem cell research. These rules dictated that federally funded equipment was off limits. When the restrictions were reversed, the stickers came off, and the promise of stem cell research could be pursued more effectively.
“The federal rules forced us
to operate kind of like a kosher
kitchen,” says Evan Snyder,
M.D., Ph.D., director, Stem
Cells and Regenerative Biology.
“We just couldn’t use federally
funded equipment, no matter
how inefficient that made the
science.”
When the ban was lifted,
world attention focused on
Burnham and other leaders in
stem cell research. The Wall
Street Journal, Fox Business
News, the BBC and many
other news outlets came to
Torrey Pines Mesa to find out
what these changes meant for
current science and future
treatments. For the scientists
who have dedicated their
careers to stem cell research,
this new freedom means
expanded opportunities to
translate stem cells into cures.
hOW dO sTEM cELLs FUNcTION?
One of the goals
of the Stem Cell and
Regenerative Biology
program is to under-
stand the processes
that help stem cells
decide whether to
differentiate, or not,
and what type of
tissue they should
differentiate into.
Alexey Terskikh,
Ph.D., is inves-
tigating the earliest neural
pathways taken by
differentiating embryonic
stem cells. He notes that cells
derived from the neural crest
(embryonic cells that give rise
to neurons, skeletal elements,
smooth muscle, etc.) become
peripheral cells throughout the
body—but how is that specifi-
cation acquired?
“When they start migrating,
they’re all the same. But then
they become specialized; they
know what they’re supposed to
do,” says Dr. Terskikh.
The ultimate goal is to
create cells for clinical use.
The Terskikh laboratory has
developed a protocol to rapidly
differentiate human embry-
onic stem cells into neural
progenitor cells that may be
ideal for transplantation. Their
research, published in Cell
Death and Differentiation,
could be adapted to produce
committed neural precursor
cells, one of the key require-
ments for clinical use.
TaRGETING BRaIN TUMORs
Recently, Evan Snyder,
M.D., Ph.D., in collaboration
with Mitchel Berger, M.D.,
chair of the UC San Francisco
Del E. Webb Neuroscience, Aging and
Stem Cell Research Center
When President Barack Obama reversed the federal restrictions on funding for
embryonic stem cell research, he raised the hopes of millions of people
around the world…Now that these unnecessary, indeed harmful, regulations have
been removed, American researchers can ethically and conscientiously pursue
these advances, accelerated by access to federal research funds.
Burnham President and CEO John C. Reed, M.D., Ph.D.,
in a March 27, 2009, op-ed in the San Diego Union-Tribune
Dr. Alexey Terskikh
Neural stem cells from the Terskikh laboratory.
Department of Neurosurgery, received a
disease team grant from the California
Institute for Regenerative Medicine.
The team, which includes the
Ludwig Institute, UC San Diego, and
UCLA, received more than $19 million
to study using neural stem
cells—genetically engineered
to contain a tumor-killing
gene—to home in on glio-
blastoma multiforme. This
approach is based on Dr.
Snyder’s discovery that stem
cells seek out cancer cells,
including primary and meta-
static brain tumor cells. In
addition, Dr. Snyder discov-
ered that stem cells could be
engineered to deliver a range
of genes, including tumor-
killing genes. The goal is to
launch a clinical trial within four years.
PROGREss ON NEUROdEGENERaTIVE dIsEasEs
There is a direct relationship between
how a protein is folded and what that
protein does. Many diseases can trace
their roots to problem proteins. This is
particularly true in neurodegenerative
diseases, which are commonly caused by
misfolded proteins.
Recently, Stuart Lipton, M.D.,
Ph.D., director of the Del E. Webb
Center for Neuroscience, Aging and
Stem Cell Research and colleagues
found that normal synaptic activity
in nerve cells (the electrical activity
in the brain that allows nerve cells to
communicate) protects the brain from
the misfolded proteins associated with
Huntington’s disease. They also found
that the drug Memantine, which is
approved to treat Alzheimer’s, success-
fully treated Huntington’s disease in
mice by preserving normal synaptic elec-
trical activity and suppressing excessive
extrasynaptic electrical activity.
“We show here, for the first time,
that electrical activity controls protein
folding, and if you have a drug that can
adjust the electrical activity to the correct
levels, you can
protect against
misfolding,”
says Dr. Lipton.
“This verifies
that appropriate
electrical
activity is
protective,
supporting the
concept of the
‘use it or lose
it theory’ of
brain activity at
the molecular
level. Published in Nature Medicine, this
finding may explain why epidemiologists
have found that ‘using’ your brain by
performing crossword puzzles and other
games can stave off cognitive decline in
diseases like Alzheimer’s.”
Burnham researchers also made prog-
ress in understanding Alzheimer’s disease.
Huaxi Xu, Ph.D., acting director of the
Neurodegenerative Disease Research
program, and others identified a novel
mouse gene that reduces the accumula-
tion of two toxic proteins that are major
players in Alzheimer’s: amyloid beta and
tau. Amyloid beta is responsible for the
plaques found in the brains of Alzheimer’s
patients. Tau causes the tangles found
within patients’ brain cells. The study
was published in Neuron.
“From the point of view of treating
Alzheimer’s disease, if we can express
the mouse gene in human brain cells,
we may be able to control the buildup
of amyloid beta and tau neurofibrillary
tangles,” says Dr. Xu.
B U r n h a m T h E y E a R I N T R a N s L a T I O N
www.burnham.org | The BUrnham reporT 5
Dr. Huaxi Xu
Other Research Highlights
Proteins play a key role in determining stem
cell fates, and phosphorylation (the biochemical
process that modifies proteins by adding a phos-
phate molecule) is central to protein activity.
EVaN sNydER, M.d., Ph.d., director of
Burnham’s Stem Cell and Regenerative Biology
program, and LaURENcE BRILL, Ph.d., and
others have catalogued 2,546 phosphorylation
sites on 1,602 phosphoproteins. Identifying these
sites will help us understand the mechanisms
that influence self-renewal and differentiation.
Published in Cell Stem Cell.
A great deal of work has been done on aging as
a systemic process throughout the body, but now
researchers are looking more closely at how aging
affects individual organs. ROLF BOdMER, Ph.d.,
director, Development and Aging, has found
that the protein d4eBP controls cardiac aging
in Drosophila (fruit flies). The team also found
that d4eBP protects heart function against aging.
Published in Aging Cell.
GREGG dUEsTER, Ph.d., xIaNLING zhaO,
Ph.d., and colleagues have clarified the role
that retinoic acid plays in limb development.
The study showed that retinoic acid controls the
development (or budding) of forelimbs, but not
hindlimbs, and that retinoic acid is not respon-
sible for patterning (or differentiation of the parts)
of limbs. This research corrects longstanding
misconceptions about limb development and
provides new insights into congenital limb defects.
Published in Current Biology.
ThE LIPTON LaBORaTORy has demonstrated
that attacks on the mitochondrial protein Drp1
by the free radical nitric oxide—which causes a
chemical reaction called S-nitrosylation—mediates
neurodegeneration associated with Alzheimer’s
disease. Prior to this study, the mechanism by which
beta-amyloid protein caused synaptic damage to
neurons in Alzheimer’s disease was unknown. These
findings suggest that preventing S-nitrosylation of
Drp1 may reduce or even prevent neurodegeneration
in Alzheimer’s patients. Published in Science.
B U r n h a m T h E y E a R I N T R a N s L a T I O N
6 The BUrnham reporT | www.burnham.org
NEW sTRaTEGIEs, NEW INsIGhTs
Viruses may have invented
planned obsolescence.
Humans, and other higher
organisms, have sophisticated
error-correction mechanisms
to carefully limit the number
of mutations in our DNA.
Not so with viruses. In fact,
they are designed to mutate
to better evade our immune
systems. But occasionally, a
viral protein is resistant to
mutation because its function
is so complex any changes
would render it useless.
In February, Robert
Liddington, Ph.D., director,
Infectious Disease Program,
along with collaborators at the
Dana-Farber Cancer Institute
and the Centers for Disease
Control, found such a vulner-
ability in the influenza virus.
The team identified human
monoclonal antibodies that
neutralize numerous influenza
viruses, including bird flu,
previous pandemic influenza
viruses and potentially H1N1.
The study was published
in Nature Structural and
Molecular Biology.
“The head portion of
hemagglutinin (the protein
that binds the virus to a cell)
is highly changeable, leading
to forms of the virus that can
evade neutralizing antibodies,”
says Dr. Liddington. “However,
the stem region of hemag-
glutinin is highly conserved
because it undergoes a dramatic
conformational change to allow
entry of viral RNA into the host
cell. It’s very difficult to get a
mutation that doesn’t destroy
that function,
which explains
why these
antibodies
neutralize
such a variety
of influenza
strains.”
The ripples
from this
paper were
felt worldwide.
With interna-
tional concern
over the
avian flu, the
possibility that
researchers
might have found a way to
target multiple influenza strains
garnered considerable interest.
Hundreds of news outlets,
including CNN, the New York
Times and Time Magazine,
reported on this breakthrough,
and interest continued for
several weeks.
As fall approached and
H1N1 (swine) flu became
a growing concern, there
was renewed interest in
this research. In October,
Burnham sponsored an
experts panel to sort fact from
fiction in the H1N1 discus-
sion. The panel featured Dr.
Liddington; Steve Waterman,
M.D., medical epidemiologist
for the Centers for Disease
Control; Patricia Skoglund,
R.N., administrative director
of Disaster Preparedness for
Scripps Health; and Nathan
Fletcher, state assemblyman
representing California’s 75th
District. The panel was moder-
ated by former San Diego
newscaster Carol LeBeau. The
Infectious and
Inflammatory Disease Center
Dr. Robert Liddington
Image of the influenza virus hemagglutinin bound to neutralizing antibodies (in red). Most antibodies
bind to the head region, which is highly variable. However, the stalk region cannot mutate because it
is part of a complex molecular machine required to enter the cell. Liddington laboratory
B U r n h a m T h E y E a R I N T R a N s L a T I O N
www.burnham.org | The BUrnham reporT 7
Other Research HighlightsaNdREI OsTERMaN, Ph.d. , in collaboration with the
University of Texas Southwestern Medical Center and University of
Maryland, demonstrated that an enzyme essential to the survival of
many bacteria can be targeted by chemical compounds that inhibit
the enzyme and suppress bacterial growth. These findings are essen-
tial to developing new antibiotics to overcome multidrug resistance.
Published in Chemistry and Biology.
GIOVaNNI PaTERNOsTRO, M.d., Ph.d., adjunct professor
in Burnham’s Cancer Center, and colleagues showed that search
algorithms used in digital communications can help scientists iden-
tify effective multi-drug combinations, particularly combinatorial
cancer therapies. As personalized medicine moves from the present
emphasis on diagnosis and prognosis to therapy, physicians will need
to find drug combinations that are uniquely suited to the genetic
and molecular profile of each patient. This research is a first step in
that direction. Published in PLoS Computational Biology.
ROBERT RIckERT, Ph.d. , and colleagues have provided
evidence that suppressing the PI3-kinase signaling pathway is a
hallmark of anergic (inactivated) B cells. This work sheds light on
the biochemical basis of B cell anergy and may provide insights into
human autoimmune diseases characterized by broad autoantibody
production. Published in Immunity.
sUMIT chaNda, Ph.d. , and colleagues have assembled
an encyclopedia of cellular proteins reported to be important for
HIV replication. Using interaction mapping and bioinformatic tools,
the team identified biochemical complexes and biological pathways
that were common to these studies. This study reconciles previously
published host/pathogen interaction data and provides an important
road map to develop host factor-mediated antivirals. Published in
PLoS Pathogens.
hour-long event discussed flu
dangers, distinctions between
flu varieties, vaccinations,
common sense precautions
and how state and local orga-
nizations and agencies are
preparing for the flu. The event
was videotaped by UCSD-TV
and can be found, along with
a web chat on the flu with Dr.
Liddington, at www.burnham.
org/pandemicflu.
MaPPING a PROTEIN NETWORk
There are various ways
to test a hypothesis: in vitro
methods use cells in a dish
or test tube; in vivo uses a
living organism. Burnham’s
Bioinformatics and Systems
Biology Program is helping
develop another method: in
silico, or in a computer. Adam
Godzik, Ph.D., with colleagues
at UC San Diego, The Scripps
Research Institute, Genomics
Institute of the Novartis
Research Foundation and
other institutions, recently
constructed a complete model,
including three-dimensional
protein structures, of the central
metabolic network of the bacte-
rium Thermotoga maritima (T.
maritima). Published in Science,
this is the first time researchers
have developed such a compre-
hensive model of a metabolic
network overlaid with an atomic
resolution of network proteins.
Combining biochemical
studies, structural genomics
and computer modeling, the
researchers deciphered the
shapes, functions and interac-
tions of 478 proteins that
make up T. maritima’s central
metabolism.
“We have built an actual
three-dimensional model of
every protein in the central
metabolic system,” says Dr.
Dr. Adam Godzik
Godzik, director, Bioinformatics
and Systems Biology Program.
“We got the whole thing. This
is analogous to sequencing an
entire genome.”
This information has the
promise to expand computer
modeling to allow investigators
to simulate the interactions
between proteins and various
compounds in an entire system.
Furthermore, the procedure
developed in this study could
be applied to study many other
organisms, including humans.
It could potentially help identify
both positive and adverse drug
reactions before pre-clinical and
clinical trials.
NEW FacILITy, NEW cOLLaBORaTIONs, NEW scIENcE
On October 8, more than 900 people, including Florida
Governor Charlie Crist, helped Burnham dedicate our new
175,000-square-foot scientific facility at Lake Nona in Orlando,
Florida. This is the first facility to open in Lake Nona’s Medical
City, which will be a hub for medical research to advance scien-
tific discoveries and breakthrough therapies.
“We have established a foundation by bringing new expertise
to the region and
forging strong
alliances that
will enhance and
accelerate scientific
opportunities,” said
John Reed, M.D.,
Ph.D., president
and CEO, professor
and Donald Bren
Presidential Chair.
“Burnham’s collab-
orative approach
has been very successful. We are transferring that model to the
Lake Nona campus in Orlando, where scientists are conducting
research in metabolic disorders, heart disease and cancer.”
Burnham’s Lake Nona facility was designed to maximize an
array of sophisticated technolo-
gies that will help researchers
answer some of the most funda-
mental questions about human
biology. The Conrad Prebys
Center for Chemical Genomics
facility at Lake Nona, like its
counterpart in La Jolla, will iden-
tify small molecule compounds
that can help regulate proteins implicated in disease (see page
11). In addition, the Cardiovascular Pathobiology and Metabolic
Signaling and Disease programs will study type 2 diabetes, heart
disease and other conditions. This will be supported by the
Cardiometabolic Phenotyping Core, which will study cardiovas-
cular complications and metabolic disturbances in mouse models
of human diseases.
METaBOLOMIcs
Researchers are particularly excited about the new facility’s
emerging metabolomics capability. Burnham is collaborating with
the Sarah W. Stedman Nutrition and Metabolism Center (Stedman
Center) at Duke University Medical Center to use metabolite
profiling to clarify the basic mechanisms of disease, identify
biomarkers for diagnosis and monitor treatment. The recent agree-
ment establishes an extension of Duke’s Stedman Center laboratory
at Burnham’s Lake Nona campus and combines the Stedman
Center’s metabolomics expertise with Burnham’s complementary
technologies. But what is metabolomics?
“Metabolomics is the survey of the small molecule metabolites
in the body,” says Stedman Center Director Christopher Newgard,
Ph.D. “I think a good way to describe it is the chemical fingerprint.
What we’re really talking about is the fundamental way that we
process genetic information. It starts at the gene, then you make
messenger RNA, you make proteins, but the end result of all of that
genetic machinery is to affect
the chemistry of the body.”
In short, metabolomics will
provide a rapid way to analyze
chemicals (metabolites)
in the body and determine
the processes that created
those chemicals. Once these
compounds have been traced
to their genetic source, clinicians will use these metabolite
profiles as a powerful diagnostic tool to uncover diseases at their
earliest stages and determine the specific nature of the disease.
Dan Kelly, M.D., Scientific Director of Burnham at Lake Nona,
sums up the importance of this technology: “How do we begin to,
identify the individual who’s most at risk for developing diabetes? Can
B U r n h a m T h E y E a R I N T R a N s L a T I O N
8 The BUrnham reporT | www.burnham.org
Diabetes and Obesity Research Center
Florida Governor Charlie Crist and Malin Burnham at the dedication ceremony
Burnham’s Lake Nona facility was designedto maximize an array of sophisticated
technologies that will help researchers answer some of the most fundamental questions about human biology.
Greg Lucier, Dr. John Reed, Malin Burnham and Dr. Daniel Kelly tour the Conrad Prebys Center for Chemical Genomics.
we come up with personalized markers? The Stedman Center has
already begun to find chemical markers that identify individuals who
might go on to develop insulin resistance and diabetes. This technology
could also be applied to heart disease and different forms of cancer—
both in making a diagnosis and looking at the severity of the disease.
“The bottom line is: how do we individualize treatment?”
cOLL aBORaTIONs
Collaborating with clinical institutions is a key element of
Burnham’s strategy to rapidly move discoveries from the laboratory to
the clinic. In fact, just prior to the dedication ceremony, the University
of Florida announced that they too will build a facility in the Medical
City. Their presence will add additional firepower to an already potent
lineup of Burnham partners, including M.D. Anderson Cancer Center
Orlando and the University of Central Florida.
The Florida Hospital-Burnham Translational Research Institute
(TRI) is a great example of how these basic research/clinical part-
nerships will work. The TRI combines scientists and clinicians with
incredible technologies to enhance translational research and bring
new treatments to patients. Recently, Steven R. Smith, M.D., was
recruited as the TRI’s executive director, one of many new faculty
brought to Lake Nona in 2009.
Dr. Smith’s work bridges the gap between cellular and molecular
biology and clinical care. His research is focused on obesity, diabetes
and the metabolic origins of cardiovascular disease. Specifically, Dr.
Smith investigates why some people burn fat when fed a fatty diet
while others fail to burn fat and develop health problems like diabetes.
He is also trying to understand how obesity leads to type 2 diabetes and
examining the relationship between inflammation and diabetes.
“We recently discovered that in some obese people, adipose
(fat) tissue becomes hypoxic (starved of oxygen) because there are
not enough small blood vessels,” says Dr. Smith. “This leads to
inflammation in adipose tissue. There is a growing body of science
that shows that inflammation is a major player in the development
of type 2 diabetes.”
On the clinical side, Dr. Smith wants to identify and validate
drugs to treat obesity and diabetes. His translational work has
demonstrated that everyone is unique at the molecular level,
suggesting new ways to match therapies to the individual—in
other words, personalized medicine.
“One new area that I will be working on in Florida is using anti-
obesity drugs to treat diabetes,” says Dr. Smith. “We know that the
first 10 to 15 pounds lost has a big impact on blood sugar control
and metabolism. Many diabetes drugs cause weight gain. Since
most people become diabetic because they are overweight, we
believe that weight gain is not a desirable effect of diabetes drugs.
Weight loss can also prevent the development of diabetes.”
B U r n h a m T h E y E a R I N T R a N s L a T I O N
www.burnham.org | The BUrnham reporT 9
Dr. Steven R. Smith
dR. daNIEL kELLy hONOREd FOR GROUNdBREakING REsEaRch
Burnham at Lake Nona’s Scientific Director Daniel
P. Kelly, M.D., has been awarded the American Heart
Association’s 2009 Basic Research Prize, which recognizes
his work on molecular biology and the physiology of cardiac
metabolism and his vision of how basic research can trans-
late into treatments.
Dr. Kelly’s research focuses on problems in cardiac
energy metabolism. His investigations outline metabolism
in normal and diseased hearts and the impact of obesity
and diabetes on cardiac function. His pioneering work in
fuel and energy metabolism is defining new classes of drug
targets and sets the stage for more personalized therapies.
Burnham at Lake Nona
B U r n h a m T h E y E a R I N T R a N s L a T I O N
Sanford Children’s Health Research Center
In late 2007, the Sanford Children’s Health Research Center was established at Burnham’s San Diego campus with a $20 million gift from South Dakota philanthropist Denny Sanford through Sanford Health. The gift was the foundation for a long-term collaboration between Sanford Health of Sioux Falls, South Dakota, and Burnham.
The collaboration combines world-class scientific talent with
state-of-the art technology to conquer childhood diseases like
type 1 diabetes, muscular dystrophy and many others. In addition
to the center in La Jolla, Sanford Health has created a Children’s
Health Research Center in Sioux Falls. Together, Burnham and
Sanford Health are establishing an integrated, academic/pediatric
research network.
Recently, Sanford researchers from Sioux Falls and La Jolla
met for the Second Annual Sanford Scientific Symposium to share
their research and discuss how best to move forward with efforts
to cure childhood diseases. Held at Burnham’s La Jolla campus,
the symposium addressed the convergence of basic scientific and
clinical research and how the collaborations between Burnham
and Sanford Health could lead to new treatments.
“This collaboration is working on many levels,” says Fred
Levine, M.D., Ph.D., director, Sanford Children’s Health
Research Center. “Scientists from Sioux Falls and Burnham are
periodically comparing research findings. One scientist from La
Jolla has been recruited to Sioux Falls, and others are applying
for positions there. So we are developing the cross-pollination we
hoped to achieve, and that will lead to new and important insights
into childhood diseases.”
10 The BUrnham reporT | www.burnham.org
Other Research HighlightsTaRIq RaNa,
Ph.d. , recently showed
how a microRNA (a
short, noncoding strand
of RNA) plays a key role
in controlling the HIV
life cycle by transporting
HIV messenger RNA to
processing bodies inside
cells, where it is stored
or destroyed. This results
in a reduction of viral
replication and infectivity.
While, on the surface, this may seem like a good result, Dr. Rana
believes that HIV may be co-opting this cellular defense mecha-
nism to help the virus hide from immune defenses and antiviral
drugs. Published in Molecular Cell.
PaMEL a ITkIN- aNsaRI , Ph.d. , and colleagues recently
demonstrated in mice that transplanted pancreatic precursor
cells are protected from the immune system when encapsu-
lated in polytetrafluorethylene, suggesting a new approach
to treating type 1 diabetes. Dr. Itkin-Ansari showed that the
precursor cells matured into functional beta cells that were
glucose-responsive and
controlled blood sugar levels.
Published in Transplantation.
yU yaMaGUchI, M.d. ,
Ph.d. , along with collabo-
rators at the University of
Connecticut Health Center,
showed that mice, in which
the gene Has2 was inactivated
in the limb bud mesoderm,
had shortened limbs, abnormal
growth plates and duplicated
bones in fingers and toes. The
Yamaguchi laboratory genetically modified the Has2 gene so that
the gene can be conditionally disrupted in mice. This is the first
time a conditional Has2 knockout mouse has been created, a
breakthrough that opens vast possibilities for future research.
Published in Development.
JOsé LUIs MILL áN, Ph.d. , studies a horrible and often
fatal disease called Infantile hypophosphatasia (HPP). A rare form of
rickets, HPP makes bones dangerously fragile. When HPP patient
“Baby Amy” was flown from her home in Ireland to Winnipeg,
Canada, she was transported in an insulated box to prevent her bones
from breaking. However, after receiving an enzyme replacement
therapy developed by Dr. Millán and others, she was healthy enough
to be held by her mother and make the trip home to Ireland.
Dr. Yu Yamaguchi
Dr. Tariq Rana
IN sEaRch OF NEW
MEdIcINEs
In 2001, Burnham leader-
ship, as part of the Institute’s
10-year plan, decided to pursue
the study of chemical genomics.
This decision was not without
risk, as creating the scientific
infrastructure would require a
large capital investment. On
the other hand, the potential
rewards were immense. Much
of the science at Burnham
involves asking important ques-
tions about how genes and
proteins function. Chemical
genomics is a powerful way
to answer many of those
questions.
Now, eight years later,
scientists at the Conrad
Prebys Center for Chemical
Genomics are carrying out
the formidable task of finding
chemical compounds that can
alter protein function. Robotic
screening systems test large
chemical libraries (with nearly a
half million compounds) against
biological material—like a
single protein or a specific type
of cancer cell. These screens
are intended to find the handful
of molecules that can regulate
a specific gene or protein by
turning it on or off.
A chemical “hit” can have a
number of uses. The ability to
manipulate a protein can help
researchers determine what that
protein does. In some instances,
a compound may have drug-like
properties that can be optimized
by medicinal chemists and
pharmacologists and perhaps
advanced to clinical trials.
a sOUNd dEcIsION
Burnham’s expertise in
chemical genomics has been
recognized nationwide and has
become a magnet for public
and private investment. In
September 2008, Burnham was
awarded a $98 million grant
to establish a comprehensive
screening center as part of the
National Institute of Health’s
Molecular Libraries Probe
Production Centers Network—
one of only four such screening
centers in the country.
In early 2009, Burnham
signed an assay develop-
ment and license agreement
with Johnson & Johnson
Pharmaceutical Research
and Development (J&JPRD),
Burnham’s first broad-based
partnership with a large phar-
maceutical company. Under this
multi-year agreement, Burnham
will provide J&JPRD with
access to screening technologies
to investigate drug targets for
inflammatory diseases.
In January 2009, Conrad
Prebys donated $10 million
to name the screening center.
For Prebys, a longtime San
Diego real estate developer, the
decision to support chemical
genomics was built on his desire
to make a significant impact.
“I lost four close friends
to cancer last year—one to a
leukemia I didn’t even know
existed,” said Prebys at the time
of his gift. “I have been very
blessed in my life, and some
times I wonder why. The only
answer I can come up with is
that I’m here to do some good in
the world.”
MOVING dIscOVERIEs
TO ThE cLINIc
Burnham recently
appointed Michael R. Jackson,
Ph.D., to the newly created
position of vice president
for Drug Discovery and
Development. In this role, Dr.
Jackson will oversee the chem-
ical biology and drug discovery
efforts at the Prebys Center
facilities in La Jolla and Lake
Nona. He will lead Burnham’s
efforts to identify drug candi-
dates—developing promising
chemical compounds into new
medicines and creating part-
nerships for preclinical and
clinical drug development.
www.burnham.org | The BUrnham reporT 11
B U r n h a m T h E y E a R I N T R a N s L a T I O N
Conrad Prebys Center for Chemical Genomics
“The idea of saving just one life is remarkable, but
the opportunity to use this technology to find cures
that will affect millions of people, that’s incredible.”
Conrad T. Prebys
Burnham’s expertise in chemical genomics has been recognized nationwide and has become a magnet for public and private investment.
Conrad T. Prebys
Nanoparticles, like this micelle, may be the future of medicine.
scIENcE aNd scIENcE FIcTION
Burnham distinguished
professor Erkki Ruoslahti,
M.D., Ph.D., sits in his
office at UC Santa Barbara
and ponders the relationship
between science and science
fiction. He is discussing Star
Trek’s sophisticated hand-held
medical devices and all they
could do for patients.
“Ideally, you would like to
have a device like Dr. McCoy’s
that could both diagnose and
treat,” says Dr. Ruoslahti.
“I think eventually we will
have devices like small MRI
machines that can do just
that.”
Though this level of
technology is still many years
off, Dr. Ruoslahti is leading
projects that might seem
like science fiction. A former
Burnham president and CEO,
Dr. Ruoslahti established
the Burnham connection to
UCSB in 2006. He is building
on his earlier discovery that
a peptide (a piece of protein)
called RGD is attracted to cell
attachment proteins called
integrins. What makes this so
important is that tumor blood
vessels express RGD-binding
integrins, allowing researchers
to custom-make peptides that
home in on tumors.
Taking that a step further,
Dr. Ruoslahti has been
collaborating with engineers
at UC Santa Barbara to build
medicine-containing nanopar-
ticles. By combining these two
technologies, researchers hope
to create therapeutic nanopar-
ticles that home directly to
a cancer and release their
therapeutic payloads inside
the tumor.
“We have
succeeded in
putting targeting
molecules on
nanoparticle
drugs and have
shown that they
are more effec-
tive and less
toxic,” says Dr.
Ruoslahti.
FILLING IN ThE PUzzLE
Jamey Marth,
Ph.D., who
directs the new
joint Center for Nanomedicine
established by Burnham and
UC Santa Barbara, began his
career studying genes. In fact,
he helped develop Cre-loxP
technology, which is used
by researchers worldwide
to selectively remove genes
to study their functions in
specific cells and tissues at
specific times. But over time,
Dr. Marth realized that there
was more to cells than what
DNA, RNA and proteins were
teaching us.
“We have been looking to
genes to find the origins of
disease,” says Dr. Marth, “but
genomic variation has not
explained the origins of many
common grievous diseases,
such as diabetes, autoimmune
conditions and various neuro-
degenerative disorders.”
When his research
revealed that mechanisms
responsible for at least some of
these diseases were attributed
to non-genetic alterations of
cells, Dr. Marth began to see
things differently.
“Genes and proteins are
important, but cells are also
made up of two other major
structural components:
B U r n h a m T h E y E a R I N T R a N s L a T I O N
12 The BUrnham reporT | www.burnham.org
UC Santa Barbara– Burnham Center for Nanomedicine
Dr. Erkki Ruoslahti
glycans (sugars) and lipids
(fats). We need to come to a
better understanding of how
they operate and malfunction
in causing disease.”
Dr. Marth notes that
glycans and lipids are much
more difficult to study because
they are not template-driven.
In other words,
a specific
sequence
of DNA is
a template
for a specific
sequence of
RNA, which
in turn creates
a sequence of
amino acids
that build a
protein. Lipids
and glycans,
on the other
hand, are not
so easy to
trace.
“There
will continue
to be profound discoveries in
the genome, but we’re going
to miss things if we don’t look
at the cell in a more holistic,
rigorous way,” says Dr. Marth.
“We need to develop high-
throughput structural analysis
of glycans and lipids so we
can see inside that black box.
Nanotechnology is the best
way to achieve this and incor-
porating these components
more broadly into nanomedi-
cine is expected to further
enrich our current approaches
to diseases that we still have
trouble treating effectively.”
a MaRRIaGE OF BIOLOGIsTs aNd ENGINEERs
One of the main reasons
Drs. Ruoslahti and Marth set
up labs at UC Santa Barbara
was to take advantage of
the university’s world-class
engineering.
“Because of my knowledge
of homing peptides, engineers
began approaching me about
using this technology to help
target nanoparticles,” says
Dr. Ruoslahti. “I realized
that molecular biology and
chemistry have made great
contributions to medicine, but
we needed to do more. It was
time to also focus on physics.”
When the UCSB-Burnham
Center for Nanomedicine
was created in summer 2009,
it was built on the idea that
fruitful collaborations between
biologists, chemists, physicists,
engineers and others could
lead to amazing breakthroughs.
“The typical approach has
been to start from the biomed-
ical side by cherry-picking a
few talented engineers and
moving them out of their
comfort zone into a biomedical
research environment,” says
Dr. Marth. “But here we have
done the opposite and started
with an environment rich
with superb engineers. We
are creating a collaborative
environment without walls
between disciplines and that
will lead to new approaches
and new knowledge and will
give us the best opportunities
to develop needed advances in
diagnostics and therapeutics
for disease prevention, treat-
ment and cure.”
B U r n h a m T h E y E a R I N T R a N s L a T I O N
www.burnham.org | The BUrnham reporT 13
What is Nanomedicine?
Dr. Jamey Marth
Rudolph Virchow, the father of pathology, noted that “all
diseases are reducible to active or passive disturbances of cells.”
Unfortunately, most medical technologies are designed to func-
tion more on the macro than the cellular level. Surgery deals with
large masses of cells or entire organs. Many medicines, including
chemotherapies, are delivered through the bloodstream and affect
most of the body. Radiation, both for treatment and diagnosis, also
works on a larger scale.
On the other hand, biological research over the past 50 years
has focused on key parts of the cell, including genes and proteins.
Nanomedicine seeks to redefine treatment and diagnosis by
engineering microscopic devices with multiple functions to focus
on the cellular roots of disease. Using impossibly tiny machines
(some as small as a nanometer, one millionth of a meter),
researchers and physicians hope to diagnose and treat cancer,
diabetes and heart disease; repair tissue damaged by trauma; and
diagnose life-threatening conditions on the cellular level, long
before there are recognizable symptoms.
Greg Lucier knows biotechnology. As Chief Executive Officer of Life Technologies (the parent company of Invitrogen and Applied Biosystems), one of the world’s largest providers of systems, reagents and services to support biomedical research, Lucier under-stands what it takes to succeed in the labora-tory. In fact, you can hardly turn a corner at Burnham without seeing Life Technologies products being used to perform critical experiments.
Lucier has been a
Burnham trustee since
2005 and succeeded Malin
Burnham as board chair in
October. He chose to volun-
teer his time and effort at
Burnham for several reasons.
Naturally, the Institute
provides a great complement
to his “day job.” Lucier was
also attracted to Burnham
by the Institute’s strong
leadership.
“I have been really
impressed by Dr. Reed, Dr.
Vuori and others,” says Lucier.
“I like working with the best,
and Burnham has the best.”
But most importantly, he
is a fervent believer in the
work that Burnham accom-
plishes every day.
“Basic research
is the foundation for
future commercial
application,” says
Lucier. “A devel-
oped country like
the United States
is morally bound to
fund basic research
because of the multi-
plier effect. Whether
the multiplier is
saving lives by curing
disease, coming up
with new methods to
improve food produc-
tion or finding new
ways to make fuel
from biological mate-
rials, this is critically
important work.”
a BUsy sEasON
Lucier takes over board
leadership at a very hectic time.
One of his first duties was
helping dedicate Burnham’s
new Lake Nona facility.
“I was blown away by the
excitement at Lake Nona,”
says Lucier. “The facility looks
great, but I was really impressed
by how passionate the entire
community is. Scientists,
administrators, government
leaders, local supporters—they
were all ready to go.”
In addition to opening the
Lake Nona facility, Burnham
expanded its presence at UC
Santa Barbara and acquired
new facilities on Torrey Pines
Mesa. Lucier knows there is a
great deal to be accomplished
in the next few years, but feels
strongly that Burnham has
the right people in place for
continued success.
LOOkING FORWaRd
In the coming years, Lucier
sees Burnham playing a signifi-
cant role in redefining how
biomedical research is done.
“I believe we are going to
see new models for research,”
says Lucier. “We have the
opportunity to bring together
universities, independent
academic institutions, contract
research organizations, phar-
maceutical companies and
other organizations to advance
the science and bring us closer
to new treatments. We are
already seeing this kind of
collaboration, both in La Jolla
and Lake Nona, and it is our
job to make sure we continue
to expand those partnerships.”
Lucier notes that he and
the other members of the
board of trustees are very
excited about where Burnham
is going.
“Our role is to work with
Burnham leadership to bring
the organization to the next
level, just as previous boards
have done. We’re here to look
after the short and long-term
welfare of the institution
through advice, financial
support, moral support and
good governance. This is
an incredible moment in
Burnham’s history, and I am
very pleased to be a part of it.”
14 The BUrnham reporT | www.burnham.org
p h I l a n T h r o p y U P d a T E
Meet Greg Lucier
www.burnham.org | The BUrnham reporT 15
p h I l a n T h r o p y U P d a T E
The Power to Cure Gala 2009
On Saturday, November 14, more than 250 people gathered at the Hyatt Regency La Jolla Aventine for The Power to Cure Gala.
The Hyatt ballroom was
draped in deep blue, floor
to ceiling fabric, and micro-
scopic images from Burnham
laboratories, printed on 8-foot
canvases, transformed the
ballroom into a science gallery.
During the live auction, the
fund-a-need raised support for
Burnham’s work in
cancer, infectious
and inflammatory
diseases, childhood
diseases, aging and
neurodegeneration.
Also, guests bid on
vacations, an intern-
ship in Dr. John
Reed’s laboratory and
dinner at the exclu-
sive French Laundry restaurant
in Napa Valley.
In all, the gala raised more
than $950,000 to support
medical research.
Many thanks to gala co-
chairs Caroline Nierenberg
and Kathryn Stephens and
presenting sponsor Life
Technologies. For information
about the Burnham Gala or
to make a donation, please
contact Chelsea Jones at
858-795-5239 or cjones@
burnham.org.Gala co-chairs Kathryn Stephens and Caroline Nierenberg
Lydia McNeil raises her bid card T. Denny Sanford Peggy and Peter Preuss
Dr. John Reed Joan and Brent Jacobs
On October 15, the Fishman Fund awarded grants to five Burnham postdoctoral fellows to recognize their commitment to biomedical science. The researchers each received $5,000 to further their education and career development. The Fishman Fund was created by philanthropists Mary Bradley and Reena Horowitz to advance science and honor Burnham founders Dr. William and Lillian Fishman.
During their postdoc-
toral fellowships, young
researchers receive training
and hands-on experience as
they launch their scientific
careers. This year’s honorees
investigate fundamental
biological processes that
may yield new insights into
cancer, heart disease, HIV
and other conditions.
dR. PIL aR cEJUdO-
MaRTIN , of the Courtneidge
laboratory, seeks to under-
stand the roles certain
proteins play in mammalian
development. This work may
also be applicable to Frank-
Ter Haar syndrome, in which
one of these proteins is
mutated and patients do not
live beyond their teens.
dR. MaRTIN dENzEL ,
of the Ranscht laboratory,
investigates how different
organs communicate with one
another. Specifically, he is
analyzing the cardiovascular
role of adiponectin, a hormone
secreted by fat tissue.
dR. FaBIaN FILIPP ,
of the Jeff Smith laboratory,
uses magnetic resonance
spectroscopy to take a “snap-
shot” of all metabolically
p h I l a n T h r o p y U P d a T E
16 The BUrnham reporT | www.burnham.org
An Avid SupporterMore than 100 people attended the reception to honor these scientists, among them philanthropist Sascha Siegel, a Fishman Fund supporter.
“What better way to further humanity than to support the career of a young scientist entering the world of research,” says Siegel, who learned the value of giving back to her community during World War II in England. Her family home had been destroyed during a bombing raid and, at 17, she volunteered to
be an ambulance driver. Later she became a military intelligence officer in the British Army.
“All the men, including my brothers, had left home to fight for Britain,” says Siegel. “It was then I real-ized the need to give back.”
Siegel moved to the United States
in the 1940s and built a family and a career as a fashion designer and television talk show host. But she has never forgotten the lessons she learned in war-torn England.
“I thought I’d open the door a little bit wider for these bright men and women by making an estate gift to the Fishman Fund so that the fund can continue to support this excellent science.”
Sascha Siegel and Lillian Fishman
Honoring Young Scientists
active compounds in a
cell. This novel approach
identifies diagnostic
markers for clinical
use and suggests new
drug targets for cancer
therapies.
dR. L aRs PachE ,
of the Chanda laboratory,
works to understand the
biological mechanisms that help HIV and influenza. The laboratory selectively silences cellular genes to determine how these genes aid or perturb viral infection. This work may eventually
lead to new treatments for
numerous pathogens.
dR. NaI -y ING
MIchELLE yaNG , of
the Pasquale laboratory,
investigates Eph proteins
in prostate and breast
cancer. These proteins
have been shown to
promote or suppress
tumor progression under
different circumstances.
p r e s I d e n T ’ s M E s s a G E
www.burnham.org | The BUrnham reporT 17
15. JohnReedessay
John C. Reed, M.D., Ph.D.
President and CEO
Professor and Donald Bren
Presidential Chair
An Amazing Year
As the year 2009 draws to a close, we reflect on our progress and take pride in the many
accomplishments that have advanced our medical research mission, giving hope to those
suffering from disease.
By all accounts, 2009 has been a great year for Burnham. Multiple breakthroughs were
made in our efforts to reveal the fundamental causes of disease and to develop innovative
prototype therapeutics.
This year, Burnham gained the top ranking in publication quality, with more cita-
tions per publication than any other organization worldwide in the fields of Biology and
Biochemistry for the decade 1999-2009 (among all organizations publishing at least 500
papers). We owe much of this success to our commitment to collaborative, team-based
science. In 2009, we surpassed the milestone of more than 500 issued patents based on
Burnham inventions. Moreover, according to U.S. government statistics, Burnham ranks
second in the nation in capital efficiency, as defined by the number of patents generated
per grant dollars spent.
This year, we grew to more than 1,000 staff and filled several key leadership positions.
Dr. Gary Raisl joined us as Chief Administrative Officer and Chief Financial Officer. Dr.
Paul Laikind is our new Chief Business Officer. Dr. Michael Jackson was recruited as
Vice President for Drug Discovery and Development. Dr. Jamey Marth came to Burnham
to direct the UCSB-Burnham Center for Nanomedicine. Dr. Tim Osborne joined us as
director of the Metabolic Disease and Signaling program at our new facility in Lake Nona.
Dr. Steve Smith directs the Florida Hospital-Burnham Translational Research Institute.
And, Dr. Steve Gardell directs Translational Research Resources. Truly, it has been an
incredible year of team building as we position our organization for future success.
In October, Malin Burnham stepped down as Board of Trustees Chair after a very
successful two-year term, and Greg Lucier has assumed that position. He will help us
develop our strategy for the next decade, as we near the end of our current 10-year plan
and begin thinking about what’s next for Burnham.
In 2009, we almost doubled our facilities, including opening our gorgeous and environ-
mentally friendly building in Orlando, acquiring a large research building in San Diego,
expanding our footprint in Santa Barbara and committing to occupy space in the Sanford
Center for Regenerative Medicine building, soon to be under construction.
Burnham is growing and prospering, thanks to much hard work and your support. Your
generosity provides the seed capital that allows Burnham scientists and supporting profes-
sionals to excel at what they do best— great science. In turn, that science provides the
basis to win the large research grants that fuel 80 to 90 percent of our biomedical research
enterprise. With so much accomplished in 2009, and with your help, we look forward with
great anticipation to advancing our medical research mission to new heights in 2010.
p h I l a n T h r o p y
Printed on recycled paper
Dieter Wolf, M.D., has an unlikely research
partner—yeast. Yet, the S. pombe fission yeast
he studies shares many genes with humans and
provides an excellent platform to understand
cell biology. In particular, Dr. Wolf is investi-
gating proteins implicated in prostate cancer.
Burnham trustee Jeanne Herberger, Ph.D.,
knows how valuable basic scientific inquiries
like Dr. Wolf ’s are to finding new treatments
for cancer and other diseases. She and her
husband, Gary, support the biomedical
research at Burnham because they see the
long-term payoff.
Partners in Science:
Dr. Dieter Wolf and Dr. Jeanne
Herberger
Nonprofit OrganizationU.s. Postage
PaIdThe Burnham Institute
“Beyond our interest in early detection and developing targeted treatments, we want to see research lead to prevention,” says Dr. Herberger. “Burnham has earned global respect with an impressive record of high-impact research and far-reaching discoveries. We are proud to lend our support.”
6400 Sanger Road
Orlando, FL 32827