Winter 2009

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From Research,The Power to Cure

I n sid e

> Burnha m R es earc h

>Ph il ant hrop y

The Year in

Translation

B U r n h a m R eport

I n T h i s I s s ue

Founders

Trustees, continued

B urn h a m R e s e a r c h

Willi am H . F ish man, Ph. D .

Lilli an F ish man

Malin Burnham Shehan Dissanayake, Ph.D. M. Wainwright Fishburn, Jr. Jeannie M. Fontana, M.D., Ph.D. David Hale Jeanne Herberger, Ph.D. Brent Jacobs James E. Jardon II (Florida) Robert J. Lauer Fred Levine, M.D., Ph.D. Sheila B. Lipinsky Papa Doug Manchester Robert A. Mandell (Florida) Douglas H. Obenshain Peter Preuss Stuart Tanz Jan Tuttleman, Ph.D., MBA Andrew J. Viterbi, Ph.D. Kristiina Vuori, M.D., Ph.D. Bobbi Warren Allen R. Weiss (Florida) Gayle E. Wilson Diane Winokur Kenneth J. Woolcott

The Year in Translation

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Honorary Trustees

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Joe Lewi s Conr ad T. P rebys T. Denn y Sa nfor d

Trustees and Officers

NCI-Designated Cancer Center

Del E. Webb Neuroscience, Aging and

Stem Cell Research Center

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Infectious and Inflammatory Disease Center

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Diabetes and Obesity Research Center

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Sanford Children’s Health Research Center

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Conrad Prebys Center for Chemical Genomics

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UCSB-Burnham Center for Nanomedicine

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P h il a nt h rop y

Meet Greg Lucier

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The Power to Cure Gala

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The Fishman Fund Awards

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F in a l t h oug h t s

President’s Message

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Partners in Science

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G reg Lucier Chairman Al an G leic h er Vice Chairman Jo h n C. R eed, M. D ., Ph. D. President & Chief Executive Officer Professor and Donald Bren Presidential Chair G a ry F. Ra i s l, Ed. D .

Executive Vice President Chief Administrative Officer Chief Financial OFficer Treasurer Marg a ret M. Dunbar Secretary

Trustees Mary Bradley Brigitte Bren Arthur Brody

Ex-Officio Raymond L. White, Ph.D. Chairman, Science Advisory Board

O n T h e Cover

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 translates 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.

B l air B lum Senior Vice President External Relations Eliza bet h G ianini Vice President External Relations Ed g a r G illenwater s Vice President External Relations C hri s L ee Vice President External Relations An dre a M os er Vice President Communications

Jo sh Bax t Editor, Burnham Report G avin & G avin Adverti s ing Design Mar k Dastrup Nad ia Borowski S c ott Meli ssa Jac obs Martin Ma nn Photography Please address inquiries to: jbaxt@burnham.org

www.burnham.org

Burnham Institute for Medical Research 10901 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

B u r n h a m Di a bete s re s e a r c h

The Year in Translation The 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).

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 definitions 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 accessible, 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 scientists 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 discoveries 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 translational research capabilities.

New scientific and administrative leadership, as well as multiple collaborations, will advance the science and help transform basic discoveries into new medicines.

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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.”

Invadopodia, seen as orange dots in this image, are found in metastatic cancer cells.

NCI-Designated Cancer Center Battling Meta stas i s 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 invadopodia. 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,

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The Sec ret World of P roteins Ubiquitination is the process that marks proteins for destruction 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, aberrant 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 understanding of how proteins collaborate and the differences between healthy and diseased cells.

Using an advanced proteomic technique called N-terminomics, Guy Salvesen, Ph.D., Dr. Sara A. Courtneidge professor and director of the Apoptosis and

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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 Dr. Dieter Wolf 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.

Other Research

Highlights

Kristiina 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 division 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.

G ary C hiang , 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 Rie dl , Ph. D., and colleagues have determined 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 mechanism in receptor signaling. Published in Nature.

Wei J iang , Ph. D., and colleagues have demonstrated important new roles for the protein kinase complex Cdc7/Dbf4 or Cdc7/Drf1 (Ddk) in monitoring damage control during : 8E:<I :<EK<I DNA replication and reinitiating replication 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.

Renewing t he NC I-Des ignation 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 initiaGIF>I<JJ FE K?< G8K? KF : 8E:<I :LI<J tion, growth and progression of cancer.”

BUR NHAM INSTITUTE for MEDICAL R ESEARCH

Burnham recently published a report on our NCI-designated Cancer Center. Progress on the Path to Cancer Cures is available by request. Contact Jane Langer at jlanger@burnham.org or 858-795-5288 to receive a copy.

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Neuroscience, Aging and Stem Cell Research Center

Del E. Webb

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

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

How Do Stem Cell s Function ?

One of the goals of the Stem Cell and Regenerative Biology program is to understand the processes that help stem cells decide whether to differentiate, or not, and what type of tissue they should differentiate into.

Alexey Terskikh, Dr. Alexey Terskikh Ph.D., is invesBurnham and other leaders in tigating the earliest neural stem cell research. The Wall pathways taken by 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.

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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 specification 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 embryonic 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 requirements for clinical use.

Targeting B r ain Tumors Recently, Evan Snyder, M.D., Ph.D., in collaboration with Mitchel Berger, M.D., chair of the UC San Francisco

Neural stem cells from the Terskikh laboratory.

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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 glioblastoma multiforme. This approach is based on Dr. Snyder’s discovery that stem cells seek out cancer cells, including primary and metastatic brain tumor cells. In addition, Dr. Snyder discovered that stem cells could be engineered to deliver a range of genes, including tumorkilling genes. The goal is to launch a clinical trial within four years.

P rogres s on N eurod egenerative Disea ses 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, successfully 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 Dr. Huaxi Xu 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 progress 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 accumulation 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.

Other Research

Highlights

Proteins play a key role in determining stem cell fates, and phosphorylation (the biochemical process that modifies proteins by adding a phosphate 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 responsible 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.

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Infectious and

Inflammatory Disease Center New str ategies , New I n s igh t s 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 vulnerability 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 hemagglutinin 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 international concern over the avian flu, the possibility that researchers might have found a way to target multiple influenza strains garnered considerable interest.

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

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Dr. Robert Liddington

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 discussion. 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 moderated by former San Diego newscaster Carol LeBeau. The

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hour-long event discussed flu dangers, distinctions between flu varieties, vaccinations, common sense precautions and how state and local organizations 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

Other Research

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 bacterium Thermotoga maritima (T. maritima). Published in Science, this is the first time researchers have developed such a comprehensive 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 interactions 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.

Highlights

And rei O sterma n, 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 essential 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 identify 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

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.

and molecular profile of each patient. This research is a first step in that direction. Published in PLoS Computational Biology.

Robert Ri c kert, 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 C han da , 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.

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Diabetes and Obesity Research Center New Facilit y, New Coll aborations, 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 scienGreg Lucier, Dr. John Reed, Malin Burnham and Dr. Daniel Kelly tour the Conrad Prebys Center for Chemical Genomics. tific discoveries and breakthrough therapies.

“We have established a foundation by bringing new expertise to the region and Metabolomi cs forging strong Researchers are particularly excited about the new facility’s alliances that emerging metabolomics capability. Burnham is collaborating with will enhance and the Sarah W. Stedman Nutrition and Metabolism Center (Stedman accelerate scientific Center) at Duke University Medical Center to use metabolite opportunities,” said profiling to clarify the basic mechanisms of disease, identify John Reed, M.D., biomarkers for diagnosis and monitor treatment. The recent agreePh.D., president ment establishes an extension of Duke’s Stedman Center laboratory and CEO, professor at Burnham’s Lake Nona campus and combines the Stedman and Donald Bren Center’s metabolomics expertise with Burnham’s complementary Presidential Chair. technologies. But what is metabolomics?

Florida Governor Charlie Crist and Malin Burnham at the “Burnham’s collabdedication ceremony “Metabolomics is the survey of the small molecule metabolites orative approach in the body,” says Stedman Center Director Christopher Newgard, has been very successful. We are transferring that model to the Ph.D. “I think a good way to describe it is the chemical fingerprint.

Lake Nona campus in Orlando, where scientists are conducting What we’re really talking about is the fundamental way that we research in metabolic disorders, heart disease and cancer.” process genetic information. It starts at the gene, then you make Burnham’s Lake Nona facility was designed to maximize an messenger RNA, you make proteins, but the end result of all of that array of sophisticated technologenetic machinery is to affect gies that will help researchers Burnham’s Lake Nona facility was designed the chemistry of the body.” answer some of the most fundaIn short, metabolomics will to an array of mental questions about human provide a rapid way to analyze that will help researchers biology. The Conrad Prebys chemicals (metabolites) Center for Chemical Genomics some of the most in the body and determine facility at Lake Nona, like its the processes that created fundamental questions about counterpart in La Jolla, will identhose chemicals. Once these tify small molecule compounds compounds have been traced that can help regulate proteins implicated in disease (see page to their genetic source, clinicians will use these metabolite 11). In addition, the Cardiovascular Pathobiology and Metabolic profiles as a powerful diagnostic tool to uncover diseases at their Signaling and Disease programs will study type 2 diabetes, heart earliest stages and determine the specific nature of the disease. disease and other conditions. This will be supported by the Dan Kelly, M.D., Scientific Director of Burnham at Lake Nona, Cardiometabolic Phenotyping Core, which will study cardiovassums up the importance of this technology: “How do we begin to, cular complications and metabolic disturbances in mouse models identify the individual who’s most at risk for developing diabetes? Can of human diseases.

maximize technologies

answer

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sophisticated

human biology.

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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 a bor ations 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 partnerships 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.”

Dr. Steven R. Smith

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 antiobesity 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.”

Dr. Daniel Kelly Honored for Groundbreaking Researc h 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 translate 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

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Children’s Health Research Center

Sanford

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

Other Research

Highlights

Ta ri q Ra na , 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 Dr. Tariq Rana 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 mechanism to help the virus hide from immune defenses and antiviral drugs. Published in Molecular Cell.

Pa mel a I t k in- An sari , Ph. D., and colleagues recently demonstrated in mice that transplanted pancreatic precursor cells are protected from the immune system when encapsulated 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

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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.”

glucose-responsive and controlled blood sugar levels.

Published in Transplantation.

Yu Yamaguc hi , M. D., Ph. D., along with collaborators 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 Dr. Yu Yamaguchi 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 M ill 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.

B u r n h a m t h e y e a r in tr a n s l a tion

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 Conrad T. Prebys

I n Searc h of New Me d i cine s In 2001, Burnham leadership, 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 questions 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 Soun d Deci s ion 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 development and license agreement with Johnson & Johnson

Pharmaceutical Research and Development (J&JPRD), Burnham’s first broad-based partnership with a large pharmaceutical 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

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 Disc overies to the Clini c 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 chemical biology and drug discovery efforts at the Prebys Center facilities in La Jolla and Lake

Burnham’s expertise in chemical

genomics has been recognized nationwide and has become a magnet for public and private investment. 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

Nona. He will lead Burnham’s efforts to identify drug candidates—developing promising chemical compounds into new medicines and creating partnerships for preclinical and clinical drug development.

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B u r n h a m t h e y e a r in tr a n s l a tion

Dr. Erkki Ruoslahti

UC Santa Barbara–

Burnham Center for Nanomedicine Sc ienc e an d s cienc e fic tion 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

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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

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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 nanoparticles. By combining these two technologies, researchers hope to create therapeutic nanoparticles 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 effective and less toxic,” says Dr. Ruoslahti.

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 neurodegenerative disorders.”

When his research revealed that mechanisms responsible for at least some of these diseases were attributed

Filling in th e P uzzle Nanoparticles, like this micelle, may be the future of medicine.

Jamey Marth, Ph.D., who directs the new to non-genetic alterations of joint Center for Nanomedicine cells, Dr. Marth began to see established by Burnham and things differently.

UC Santa Barbara, began his “Genes and proteins are career studying genes. In fact, important, but cells are also he helped develop Cre-loxP made up of two other major technology, which is used structural components:

B u r n h a m t h e y e a r in tr a n s l a tion

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.

What is

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.

Dr. Jamey Marth “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 highthroughput structural analysis of glycans and lipids so we can see inside that black box.

Nanotechnology is the best way to achieve this and incorporating these components more broadly into nanomedicine is expected to further enrich our current approaches to diseases that we still have trouble treating effectively.”

A Marriage of Biologi st s an d 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 biomedical 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, treatment and cure.”

Nanomedicine?

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 function 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.

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P h i l a n t h r o p y up d a te

Meet

Greg Lucier

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 understands what it takes to succeed in the laboratory. In fact, you can hardly turn a corner at Burnham without seeing Life Technologies products being used to perform critical experiments.

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Lucier has been a Burnham trustee since 2005 and succeeded Malin Burnham as board chair in October. He chose to volunteer 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 accomplishes every day.

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“Basic research is the foundation for future commercial application,” says Lucier. “A developed country like the United States is morally bound to fund basic research because of the multiplier effect. Whether the multiplier is saving lives by curing disease, coming up with new methods to improve food production or finding new ways to make fuel from biological materials, 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 Forwar d In the coming years, Lucier sees Burnham playing a significant 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, pharmaceutical 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.”

P h i l a n t h r o p y up d a te

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 microscopic 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 Burnhamâ&#x20AC;&#x2122;s work in cancer, infectious and inflammatory diseases, childhood diseases, aging and neurodegeneration.

Also, guests bid on vacations, an internship in Dr. John Reedâ&#x20AC;&#x2122;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 cochairs 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

Dr. John Reed

Lydia McNeil raises her bid card

Joan and Brent Jacobs

T. Denny Sanford

Peggy and Peter Preuss

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P h i l a n t h r o p y up d a te

Honoring Young Scientists 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 postdoctoral fellowships, young researchers receive training and hands-on experience as they launch their scientific careers. This year’s honorees investigate fundamental biological processes that

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may yield new insights into cancer, heart disease, HIV and other conditions.

Dr . P il ar Ceju doMa rtin, of the Courtneidge laboratory, seeks to understand the roles certain proteins play in mammalian development. This work may also be applicable to FrankTer Haar syndrome, in which one of these proteins is mutated and patients do not live beyond their teens.

Dr . Ma rtin Den zel, 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 . Fa bi an F ilipp, of the Jeff Smith laboratory, uses magnetic resonance spectroscopy to take a “snapshot” of all metabolically

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active compounds in a cell. This novel approach identifies diagnostic markers for clinical use and suggests new drug targets for cancer therapies.

Dr . L a r s Pac h e , 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.

An Avid

Supporter More 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 realized the need to give back.”

Sascha Siegel and Lillian Fishman Siegel moved to the United States in the 1940s and built a family and Dr. Na i-Ying a career as a fashion designer and M ic h elle Yang, of television talk show host. But she the Pasquale laboratory, has never forgotten the lessons she investigates Eph proteins learned in war-torn England. in prostate and breast “I thought I’d open the door a cancer. These proteins little bit wider for these bright men have been shown to and women by making an estate promote or suppress gift to the Fishman Fund so that tumor progression under the fund can continue to support different circumstances. this excellent science.”

p r e s i d e n t ’ s M e s s a ge

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 citations per publication than any other organization worldwide in the fields of Biology and

John C. Reed, M.D., Ph.D.

Biochemistry for the decade 1999-2009 (among all organizations publishing at least 500

President and CEO

papers). We owe much of this success to our commitment to collaborative, team-based

Professor and Donald Bren

science. In 2009, we surpassed the milestone of more than 500 issued patents based on

Presidential Chair

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

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John Disease Reedand essay director of the Metabolic 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 environmentally 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 professionals 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.

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Nonprofit Organization U.S. Postage

PAID 6400 Sanger Road Orlando, FL 32827

The Burnham Institute

Philanthropy

Partners

in Science:

Wolf

Dr. Dieter and Dr. Jeanne

Herberger

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 investigating proteins implicated in prostate cancer.

“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 farreaching discoveries. We are proud to lend our support.”

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.

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