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From Research,The Power to Cure

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How Burnham Fights Cancer

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B U r n h a m R epor t

Boar d of Trustees

In T h i s I s s ue

Officers

B urn h a m C a ncer R e s e a rc h

The Life and Times of Bcl-2

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The Complexities of Cancer

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B urn h a m N ew s

Science News

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Mali n B urn ha m Chairman John C. Reed, M.D., Ph.D., President and Chief Executive Officer, Professor and Donald Bren Presidential Chair Kristiina Vuori, M.D., Ph.D., Executive Vice President for Scientific Affairs; Director, Professor, NCI Cancer Center Eric Lofgren Vice President, Finance; Chief Financial Officer; Treasurer

P h i l a n t h rop y

Donating an IRA

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Burnham Gala Nets More Than $1 Million

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Aroun d B urn h a m

Fishman Awards Honor Young Scientists

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The Curved Path: President’s Message

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Margaret Dunbar Director of Intellectual Property Management; Secretary

Trustees Linden S. Blue Mary Bradley Brigitte Bren Arthur Brody Howard I. Cohen Shehan Dissanayake M. Wainwright Fishburn Jeannie M. Fontana, M.D., Ph.D.

Trustees continued Alan Gleicher W.D. Grant David Hale Jeanne Herberger, Ph.D. Brent Jacobs James E. Jardon, II Robert Lauer Sheila B. Lipinsky Gregory T. Lucier Douglas F. Manchester Robert Mandell Nico Nierenberg Douglas Obenshain Stuart Tanz Jan Tuttleman Andrew Viterbi Bobbi Warren Allen R. Weiss Judy White Gayle Wilson Diane Winokur Kenneth J. Woolcott

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

O n T h e C over

A single breast cancer cell provides a chilling reminder of why we must find a cure. According to the American Cancer Society, 2.4 million women living in the U.S. have been diagnosed with and treated for breast cancer. Researchers at Burnham’s National Cancer Institutedesignated Cancer Center labor daily to understand the inner workings of cancer. The more we learn about what makes normal cells go wrong, the sooner we will be able to identify new chemical compounds that could lead to the next generation of treatments.

B l ai r B lum Senior Vice President External Relations Edg a r G illenwater s Vice President External Relations Eliza beth G ian ini Vice President External Relations C hr is L ee Vice President External Relations An dre a M os er Vice President Communications

Jo sh Baxt Editor, Burnham Report G avi n & G avin Advertisi ng Design Mark Dast rup Nadia Borows ki Scott 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, 8669 Commodity Circle, 4th Floor, Orlando, FL 32819 • 407.745.2000


B u r n h a m C a ncer R e s e a rc h

The Life and Times of

Bcl-Xl, a member of the Bcl-2 protein family, helps keep cancer cells alive.

Bcl-2

Anti-Cell Death Gene Has Big Impact on Cancer Research Cancer can be likened to a comic book super villain. Malignant cells divide recklessly and develop a form of immortality, making their rampant cell division even more threatening. Unlike many normal cells, which are programmed to live for a defined period, cancer cells resist these mechanisms and survive when they shouldn’t.

These days, we have a much better understanding of why cancer cells refuse to die—even when subjected to toxic doses of chemotherapy or radiation. But 20 years ago, the idea that cells could develop resistance to a natural process called apoptosis (programmed cell death) was barely part of the scientific conversation. In 1986, John Reed, M.D., Ph.D., Burnham President and CEO, Professor and Donald Bren Presidential

Chair, together with other researchers who discovered the first anti-death gene Bcl-2, began to unravel the mechanisms behind apoptosis and their relevance to cancer. What is B cl-2? The Bcl-2 gene creates a protein that works to defy cell death. Dr. Reed was a graduate student when the team he was working with recognized the importance of Bcl-2, and other cell death

proteins, to cancer. “It was a great ah-ha moment in cancer biology,” says Dr. Reed. “No one had paid much attention to the cell death side of the equation where tumor growth is concerned. When it comes to accounting for the number of cells in the body, it’s a simple case of credits and debits. Cell division makes more cells, adding to the credit side, and that was already known about cancer.

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The new revelation was that cell numbers are normally kept in check by programmed cell death—the body’s way of offsetting credits with debits to achieve a zero balance. In cancer, it’s like there’s a freeze on spending. The cancer cells refuse to die and pile up in organs until the patient is overwhelmed.” Apoptosis is particularly important in cancer because misbehaving cells are supposed

Cell division

to self-destruct to maintain order. When genes go awry, or when normally stationary cells become detached to roam freely through the body, those misbehaving cells are expected to give up their lives for the greater good. Bcl-2 and other anti-apoptotic proteins short-circuit this process, allowing these rogue cells to thrive and spread.



“For cancer cells, Bcl-2 is like having diplomatic immunity,” says Dr. Reed. “They can do whatever they want without the normal consequences that maintain an orderly society.” But even more insidious, the same mechanisms that keep these cells from dying also help them survive against our best cancer treatments. “Another important revelation was that chemo and radiotherapy induce apoptosis,” says Dr. Reed. “However, anti-apoptotic proteins protect cancer cells from these therapies. We realized that Bcl-2 could block the therapeutic effects of virtually every anticancer drug that existed, as well as radiation, and most of what the immune system can throw at the tumor.” How to B e at B cl-2 The quest to learn more about Bcl-2 and other antiapoptotic proteins illustrates the long-term value of basic biomedical research. As researchers learned more about how anti-death genes and proteins function, they began to develop ways to block their function. Continuing research has helped us understand how complex many of these cellular mechanisms are. “There are also proteins that cause cell death,” says Dr. Reed. “These two adversaries are doing hand-to-hand combat in our bodies. And when the balance of power goes awry, that’s when disease strikes.”

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Understanding How

Cancer Works The more strategies we adopt in the war on cancer, the more opportunities we will have to develop new medicines. Here’s how Burnham scientists approach the fight: Tumor Developmen t Cancer is caused by changes in our DNA sequences or how those sequences are expressed. These changes can be caused by genetic mutations or by epigenetic alterations (changes that do not alter the genome but affect the function of the genome). Understanding how genetic and epigenetic changes arise, the significance of these specific changes and the consequences of inappropriate gene regulation (when genes are turned on or off) can reveal new strategies for drug discovery. Tumor Mi croenvironmen t We now know that the growth and spread of cancer involves not just tumor cells but other host cells in the tumor microenvironment—the cellular neighborhood around cancer. For example, angiogenesis (blood vessel growth) requires the tumor to recruit surrounding blood vesselbuilding cells to enlarge its blood supply. This mechanism provides oxygen and nutrients to tumors, so they can grow, and allows cancer cells to

escape their primary site and metastasize. Learning how to alter the microenvironment could lead to new approaches against cancer. Signal Tran s d uc t i on Our cells are constantly receiving signals to grow, divide and perform many other functions. But when these signals get crossed, cells can no longer perform the jobs they’ve been assigned. In cancer, cells may ignore the instructions they’re receiving or accept entirely new instructions—to divide unchecked or migrate to another part of the body. If we can learn how these complex signals work, we can figure out ways to correct them when they go wrong. Apoptosis Finding ways to make malignant cells die, rather than escape death, holds great promise for new treatments against cancer and other diseases. Burnham research has led to a synthetic DNAbased drug that shuts off an anti-death gene in cancer cells, making them easier to kill with conventional chemotherapy. Numerous other possible therapies are under development. But it all comes down to one question: How do we convince errant cells to do the right thing and die?


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recognized Apogossypol’s potential. The National Cancer Institute has provided special support to advance the drug toward clinical trials with an award to Drs. Pellecchia and Reed through its Rapid Access to Innovative Drugs program. Also, Coronado Biosciences, Inc., has taken the Apogossypol project under its wing and is financing the manufacturing and pre-clinical toxicology studies necessary to gain FDA approval for testing in humans. Clinical trials are anticipated for early 2009. Dr. Maurizio Pellecchia’s lab has been working on Apogossypol, a drug that helps defeat Bcl-2.

One way to restore the balance in our cells is to intervene on the genomic level. Antisense technology uses synthetic DNA (or RNA) molecules to change how genes function. Genasense, one of the first DNA-based drugs to tackle a major disease, works by essentially shutting down the gene that creates the Bcl-2 protein. By reducing production of Bcl-2 in cancer cells, Genasense helps make them more vulnerable to current treatments. In other words, by defeating the cellular mechanisms that resist radiation and chemotherapy, Genasense could make those treatments far more effective. The drug, initially created by Dr. Reed and licensed by pharmaceutical company Genta, Inc.,

has completed phase III trials and is awaiting FDA approval to treat chronic lymphocytic leukemia. Neu t r al izi ng th e Prot e in Another way to beat Bcl-2 is to attack the protein rather than the gene. Dr. Maurizio Pellecchia’s laboratory has been working with Gossypol, a natural product extracted from cotton seeds, which he discovered binds to and neutralizes the Bcl-2 protein. The team chemically modified Gossypol to improve its ability to target Bcl-2, increasing its anti-cancer properties and reducing its toxicity. Dr. Pellecchia’s research strongly suggests that this new compound, Apogossypol, has great potential as a cancer treatment. In addition to spurring

cancer cells to commit suicide, the compound also makes them less resistant to chemotherapy. Dr. Pellecchia thinks Apogossypol may be used to maximize the efficacy of various chemotherapies. “Chemotherapy only kills the weak cancer cells – those with little defense against apoptosis. With each successive cycle of chemotherapy, the cells with strong anti-apoptotic defenses survive and emerge as chemo-resistant disease that ultimately kills the patient,” says Dr. Pellecchia. “Keeping the levels of Bcl-2 in check during and between chemotherapy cycles should increase the effectiveness of chemo and could prevent the cells that over-express Bcl-2 from proliferating faster.” Other organizations have

From Bad to Good In still another advance against Bcl-2 by Burnham scientists, Drs. Xiao-kun Zhang and Arnold Satterthwait created a molecule that binds to Bcl-2 and converts it from a tumor protector to a cancer cell killer. “Our results provide insight into Bcl-2 conversion and identify a new direction for Bcl-2based drugs and cancer drug development,” says Dr. Zhang. The possibility of turning this cancer friend into a cancer foe is especially appealing, as it would turn the tables on cancer, using the cancer’s self-protective shield as a weapon to help defeat it. “It’s almost like prying a shield from an attacker and clobbering them on the head with it,” says Dr. Satterthwait. “What was once the key to the cancer’s survival now becomes the means of its destruction.”

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B u r n h a m C a ncer R e s e a rc h

The Complexities of Cancer Dr. Yong Cang, Dr. Sachie Yamaji, Tiziana Lemma, Dr. Jing Zhang and Lingling Li

In 1971, President Richard Nixon declared a “war on cancer.” At the time, no one could have predicted that, nearly four decades later, we would still be fighting. Certain cancers resist our best efforts, and the treatments we have can be as bad as the disease we aim to cure. One need only spend a few minutes with a friend undergoing cancer treatment to understand we must find better treatments.



Founded as the La Jolla Cancer Research Foundation, Burnham is intently focused on finding the root causes of cancer and developing new treatments. But cancer is a wily foe, and the more we know about its many forms, the more we understand how much we need to learn. There are many dedicated scientists working on cancer at Burnham. Here is a small sample of their work. Tr ack ing Li ver Ca ncer Yong Cang, Ph.D., is deeply troubled by liver cancer. The five-year survival rate is only five percent and

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the Cang lab is busy trying to figure out why. “We know a lot about the causes—alcohol, hepatitis—we just don’t know the detailed mechanisms underlying those causes,” says Dr. Cang. The lab wants to understand why normal liver cells become cancerous, to trace the tumor’s path back to the original cancer cell and understand what made that cell go bad. “How does the hepatitis B virus protein target the liver cell protein and lead to a tumor?” asks Dr. Cang. To answer that question, the lab has been using mice that lack a specific

gene in their hepatocytes (liver cells). As expected, the mice developed tumors. But when the tumor cells were inspected, the lab found that they contained the gene that had been knocked out of the hepatocytes. In other words, removing the gene led to tumors, but the tumor cells originated away from the liver. “We found that the mutant cells change the microenvironment in the liver, which we speculate would lead to the recruitment of cells from other parts of the body to create the cancer,” says Dr. Cang. “If our model is correct, I don’t think any agent targeting the liver


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tumor will work, because even if you shrink the tumor, the initiating cells will continue to be recruited. We may have to find new targets.” Solving t he Ep h P u z zle Receptor proteins on the cell surface are extremely important because they move information inside the cell. Ligands (agents that attach to cell surface receptors) act as on switches to activate these receptors, which in turn causes a chain reaction of activities within the cell. Eph is a family of cell surface receptors that has been found to be crucial in developing embryos. It governs blood vessel growth, cell migration (the movement of nerve, bone and other cells to their proper positions within the developing embryo) and other important functions. Eph receptors are less abundant in adults—except in cancer. Elena Pasquale, Ph.D., began studying Eph function in the central nervous system but has expanded her inquiries to cancer. “We know that Eph receptors are very highly expressed in cancer tissue, but we’re only beginning to understand exactly what they are doing,” says Dr. Pasquale. The Pasquale lab has been working to inhibit the interactions between Eph receptors and their ligands, which are critical for the growth of blood

Elena Pasquale, Ph.D.

vessels that supply oxygen and nutrients to cancer cells. But there is evidence that the Eph receptors can still function in cancer cells when there’s no ligand to activate them. Dr. Pasquale is working to understand this puzzle, to find ways to also inhibit these other ligand-independent activities. However, knowing that Eph receptors are common in cancer cells has another benefit: they can become targets. Dr. Pasquale is working with Dr. Maurizio Pellecchia to develop a hybrid ligand that delivers a therapeutic drug. If the ligand homes in on Eph and the receptors are mostly present in cancer cells, this strategy could become a very efficient, targeted cancer therapy. Guidi ng Drugs to Tumor s Burnham investigator Erkki Ruoslahti, M.D., Ph.D., has helped develop a new nanoparticle that may someday be used to guide anticancer treatments directly

to tumors. Working with investigators at UCSD and MIT, Dr. Ruoslahti has taken tumorhoming peptides (chains of amino acids) and attached them to nanoparticles made from iron oxide and held together by carbohydrates. A thousand times smaller than the width of a human hair, these particles form a shell around the anti-cancer medicine, protecting it from the body’s immune system as it is ferried directly to tumors. “The idea involves encapsulating imaging agents and drugs into a protective ‘mother ship’ that evades the natural processes that normally would remove these payloads if they were unprotected,” said Dr. Michael Sailor, professor of chemistry and biochemistry at UCSD, who headed the team. Dr. Sangeeta Bhatia of MIT also played an important role. The researchers designed the particles to evade detec-

tion by constructing them of specially modified lipids (fats) — a primary component of the surface of natural cells. The lipids were modified to help the nanoparticles circulate in the bloodstream for many hours before being eliminated. Attached to the surface of the particle is a protein called F3, a molecule that sticks to cancer cells. F3 was engineered by Dr. Ruoslahti to zero in on tumor cells and transport itself into their nuclei. “We are now constructing the next generation of smart tumor-targeting nanodevices,” said Dr. Ruoslahti. “We hope that these devices will improve the diagnostic imaging of cancer and allow pinpoint targeting of treatments into cancerous tumors.”

Erkki Ruoslahti, M.D., Ph.D.

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What HIV Needs to Succeed Researchers at Burnham and Salk have identified 295 host cell factors that are involved in human immunodeficiency virus (HIV) infection. The study, published in the Oct. 3 issue of Cell, could lead to a new class of HIV therapeutics aimed at disrupting the human-HIV interactions that lead to viral infection.

The research was a collaborative effort between the laboratories of Sumit K. Chanda, Ph.D., of Burnham and John Young, Ph.D., of Salk.

Stuart A. Lipton, M.D., Ph.D., professor and director of the Del E. Webb Neuroscience, Aging, and Stem Cell Research Center at Burnham, has been awarded $8 million, over five years, to establish a Center for Neurodegeneration Science (CNS), one of three such centers in the country. Funding for the center comes from the National Institute of Environmental



“HIV has just nine genes, coding for 15 proteins, compared to bacteria, which harbor several thousand genes, or humans with over 20,000 genes,” said Dr. Chanda, associate professor in the Infectious & Inflammatory Disease Center at Burnham and an adjunct faculty member at Salk. “We have known for a long time that HIV hijacks our cellular proteins to complete its life cycle. This study now lays out its flight plan.” In the study, the team of researchers used short-interfering RNA (siRNA) which, when introduced into a cell, silences cellular gene expres-

Health Sciences. Scientists from Burnham, Scripps and UCSD will participate in the CNS Institute. Researchers at the CNS Institute will study how environmental toxins that produce free radicals (highly reactive molecules related to oxygen and nitrogen) can enhance or mimic genetic mutations that contribute to Parkinson’s disease. Specifically, the investigators will examine chemical reactions that alter protein function. A number of these

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Drs. Sumit Chanda and Renate Köenig

sion one gene at a time. More than 144,000 siRNAs were screened for their effects on HIV infection. “The integration of these systems-based analyses allowed us to build, for the first time, a functionally validated map of host-pathogen interactions that are required for viral infection,” said Renate Köenig, Ph.D., of Burnham, the first author on the study. Other coauthors included Drs. Yingyao Zhou of the

Genomics Institute of the Novartis Research Foundation, Tracy Diamond and Frederic Bushman of the University of Pennsylvania, Trey Ideker of the University of California, San Diego and Daniel Elleder of the Salk Institute for Biological Studies. The study was supported by a grant from the U.S. National Institutes of Health and the University of Pennsylvania Center for AIDS research.

New Grant Funds Parkinson’s Research proteins have already been identified. “We recently identified proteins that undergo chemical reactions in the brains of patients with Parkinson’s disease,” said Dr. Lipton. “These chemical reactions may contribute to the disease process and the chemically-

modified proteins may serve as biomarkers for disease progression. Our goal is to screen chemical libraries to find compounds that prevent free radical-induced changes to these Parkinson’s-related proteins and thus prevent Parkinson’s disease.”


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Florida Researcher Dives Deep for a Cure In September, Burnham researcher Jennifer Hoffman, with the help of the Harbor Branch Oceanographic Institute, went on a 1,300-foot dive in a small submersible to retrieve sponge samples that may be rich in anticancer compounds.

Hoffman, who works in the Burnham Lake Nona laboratory of Gregory Roth, Ph.D., is

creating synthetic anti-cancer molecules that model naturally occurring compounds in sponges. “Each day, I work in the lab focusing on designing and synthesizing new molecular compounds,” said Hoffman. “This trip put me in touch with their naturally occurring life forms.” Sponges contain a diverse collection of naturally occurring compounds, including aphrocallistin, which may lead to new treatments for pancreatic and other cancers.

Dr. Roth and Hoffman, along with Dr. Daniela Divlianska, have successfully synthesized the compound in small quantities and will now work to design more active analogs of the parent molecule. Creating the molecule synthetically will support continued research without continued ocean harvesting.

Jennifer Hoffman

The Harbor Branch submersible

High-Tech Microscope Debuts at Lake Nona Burnham recently acquired a Nikon A1si Spectral Imaging Confocal Laser Scanning Microscope System, one of only two such microscopes in the nation. For Masanobu Komatsu, Ph.D., the new microscope will be a great tool in his efforts to study the blood vessel growth associated with cancer.

Dr. Masanobu Komatsu uses Burnham Lake Nona’s new confocal microscope.

According to Dr. Komatsu, the confocal microscope provides very clear images of florescent-labeled cells. The microscope’s software analyzes structural changes in blood vessels and provides a more precise assessment than manual calculations. “It is essential to study blood vessels as 3-D structures,” says Dr. Komatsu. “The confocal’s software does the quantitative analysis to characterize the structure by assembling a series of photos into 3-D images.”

Blood vessel malfunctions and abnormal vessel growth are associated with many medical conditions, including heart disease, cancer, diabetes and macular degeneration. Dr. Komatsu is researching how to inhibit tumor growth by promoting the normal maturation of some vessels, while preventing the formation of others. This balancing act is intended to enhance drug delivery during cancer treatment, while choking the tumor and depriving it of future blood supply.

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The Sanford

Consortium On September 16, a host of dignitaries, press, researchers and others gathered in Burnham’s Fishman T. Denny Sanford Auditorium to celebrate Denny Sanford’s $30 million gift to the San Diego Consortium for Regenerative Medicine. In recognition of the donation, the Consortium has been renamed the Sanford Consortium for Regenerative Medicine. The funds provided by Sanford, combined with a $43 million major facilities grant from the California Institute for Regenerative Medicine, will be used to build and equip a new facility where scientists from Burnham, The Scripps Research Institute, Salk and UCSD will collaborate on world-class stem cell research. “I am excited to support this unique collaboration of four world-class institutions,” said Sanford. “I believe that by working together these researchers will quickly bring forward novel scientific developments that will ultimately help patients with limited or no treatment options.”

Sanford Health and Burnham to Study Glycosylation Disorders Sanford Health and Burnham are teaming up to study Congenital Disorders of Glycosylation (CDG), diseases that prevent cells from attaching sugar chains to proteins, a biochemical process that has important consequences for nearly all of the body’s functions. Because CDG affects relatively few people, they are considered “orphan” Hudson Freeze, Ph.D. diseases, as there is little financial incentive for pharmaceutical companies to study them. Burnham researcher Hudson Freeze, Ph.D., an expert on CDG, will help spearhead the collaboration. “The support from Sanford allows us to think about a global network of physicians and scientists who can coordinate their medical and research efforts,” said Dr. Freeze. “These kids are not orphans to us, they’re family.”



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

John C. Reed Heads Key NIH Committee John C. Reed, M.D., Ph.D., Burnham President and CEO, Professor and Donald Bren Presidential Chair, has been chosen to chair the National Institutes of Health’s Molecular Libraries Probe Production Centers Network (MLPCN) steering committee. Burnham was recently selected as a comprehensive small-molecule screening and discovery center, for which the Institute was awarded a $98 million grant. MLPCN centers provide innovative technologies to pursue the screening and discovery of chemical compounds that could become the next generation of medicines.

Burnham Ranks High in Workplace Satisfaction Burnham has been ranked 13th in The Scientist magazine’s 2008 survey of the best places to work in academia. In addition, Burnham ranked second in job satisfaction. PLACES This is the magazine’s sixth annual survey to TO WORK determine how tenured, permanent or tenuretrack life scientists rate the quality of their experience at their workplace. Respondents ACADEMIA were asked to assess their working environments by indicating their level of agreement with 41 criteria in eight different areas. Categories included the quality of mentoring, infrastructure and environment, pay, research resources and tenure.

BEST

2008


Philanthropy

Inheriting an IRA…

Windfall

or Tax

Trap?

By Pat t y Fuller

When you designate a beneficiary for your IRA (other than your spouse), they will pay taxes, at their own tax rate, on the amount inherited. For example, on an IRA worth $100,000, your heirs may pay as much as $35,000. And, if your estate is large enough, your heirs may lose as much as 45 percent to estate taxes or 70 to 80 percent of the entire account. Naming a charity as a beneficiary for your IRA might be the solution. It will not change required distributions during your lifetime and allows you to put your hard-earned dollars to good use. Talk to your tax advisor. It’s quite possible that you can pass on more of your assets to your heirs by using your IRA to make a charitable gift. Bruce and Marge Morrice, members of Burnham’s Legacy Society, recently designated the Burnham Institute for Medical Research as the beneficiary of their IRA. “Since Marge is a cancer survivor, it is so reassuring to know that such progress is being made in medical research,” says Bruce. “The growth of the Institute and the optimistic attitude of the faculty and administration is inspiring. “We discussed it with our financial advisors and they indicated

that our IRAs could face a double tax if we passed them on to our children. A much superior result would be to name the Institute as a recipient of the IRA on my death or the death of my survivor. “We are extremely happy with this decision and believe that this will result in a meaningful gift to the Institute and yet leave the opportunity for flexibility during the balance of our lifetime.” If you would like to make a charitable gift of your retirement account, consider naming the Institute as a primary, secondary or contingent beneficiary. When you do, 100 percent of the unused balance becomes a charitable gift. You pay no tax on the donated amount and the asset is removed from your estate. If you are married, consider naming Burnham as the second beneficiary, after your spouse. Simply fill out the beneficiary designation form provided by the plan administrator of your 401(k), Keogh, pension plan or traditional IRA, as follows: Burnham Institute for Medical Research 10901 North Torrey Pines Road, La Jolla, CA 92037 In the space provided for the beneficiary’s social security number, enter: Burnham Institute for Medical Research Employer Identification Number (EIN): 51-0197108 Scientists at Burnham Institute for Medical Research are investigating cures for a broad range of diseases that affect society. If you would like to designate an estate gift to support a specific area of research, contact Patty Fuller at (858) 795-5231, or pfuller@ burnham.org to ensure that your wishes are honored.

Remembering Eric Dudl Eric Dudl, Ph.D., had recently joined Dr. John Reed’s laboratory at Burnham as a postdoctoral fellow when he was diagnosed with a very aggressive form of lung cancer. He died a few months later in December 2006.

Eric was known for his kindness, hard work and bravery. Despite the illness, he continued his research until the very end, and his resolution in the face of pain was a source of inspiration for all who knew him. Eric was an incredible scientist with a collaborative spirit. That he was researching

cancer’s resistance to chemotherapy is a bitter irony. Eric’s parents, Barbara and Jim Dudl, established the Eric Dudl Scholarship to honor his

memory and advance biomedical research. Proceeds from the fund support continuing education for postdoctoral fellows. The battle against cancer is ongoing. By supporting young scientists, we hope to give them the tools to fight well. If you have questions about the Eric Dudl Scholarship fund, or would like to make a gift, please contact Karen Overklift at (858) 795-5288 or koverklift@burnham.org.

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Gala Nets More Than $1

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

Million

Supporters Rally Behind Burnham Researchers

Dr. John Reed, Muffy Walker, Greg and Marilena Lucier, Sue Raffee Barrett and Robin and Hank Nordhoff

Phyllis Cohn and Arthur Brody

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Dr. Andrew and Erna Viterbi


Philanthropy

Annua l Burnha m Institute for M edi cal Res earc h G al a

Guests of the Burnham Institute for Medical Research stepped back in time at this year’s gala, “Discovery Without Boundaries,” held November 15 at the Grand Del Mar Resort.

Famed scientists Albert Einstein, Louis Pasteur, Sir Isaac Newton and Leonardo da Vinci helped gala cochairs Robin Nordhoff and Sue Raffee greet guests as they embarked on an evening dedicated to modern explorers—Burnham researchers on a voyage of discovery. Guests gathered for cocktails and hors d’oeuvres on the veranda before entering the Mediterranean ballroom. Spectacular seven-foot centerpieces, by Design Essentials, graced each table. Society Beat kicked off the evening with some memorable favorites, including a solo of New York, New York sung by Burnham President and CEO, Dr. John Reed. The evening netted more than $1 million from the five live auction items, two internships and a Fund-A-Need to support post-doctoral fellowships.

Special thanks to lead table sponsors Invitrogen, Gen-Probe and Drew and Noni Senyei. Fund-A-Need raised more than $750,000, thanks to leadership gifts from T. Denny Sanford, Gary and Jeanne Herberger, Greg

and Marilena Lucier, Brent and Joan Jacobs, Art Brody and Phyllis Cohen and Malin and Roberta Burnham. “Burnham would not be complete without the inspiration and generosity of our extended family – our donors

T. Denny Sanford made a lead gift to kick off the Fund-A-Need.

and supporters,” said Dr. Reed. “It is truly an honor to be associated with individuals who are committed to making a difference in the fight against disease.”

Jeanne Jones

Burnham researchers Mari Enoksson, Ph.D., Peter Teriete, Ph.D., and Malene Hansen, Ph.D.

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Fishman Awards Honor Young Scientists Dr. John Reed and Malin Burnham

The Fishman Award winners and their supporters: Back: David Anderson, Jochen Maurer, Ph.D., Esther Paul, Melanie Hoefer, Ph.D., Patti Cooprider. Middle: Chih-Cheng Yang, Ph.D., Elizabeth RicoBautista, Ph.D., Aaron Shenkman, Judy White, Molly Jaeger Begent, Armi Williams, Eva Engvall, Ph.D., Jenny Lewis, Reinette Levine, Reena Horowitz. Front: Maria Cecilia Scimia, M.D., Erna Viterbi, Lillian Fishman, Mary Bradley

Five of Burnham’s postdoctoral research associates were recently honored with Fishman Fund Awards to recognize their commitment to basic biomedical research. The awardees receive $5,000 grants to further their education and career development as they become accomplished scientists. The Fishman Fund was created by Mary Bradley and Reena Horowitz to honor Burnham founders Dr. William and Lillian Fishman.

El izabeth Rico -Bautista , Ph. D. Working under the direction of Dr. Dieter Wolf, Dr. RicoBautista has been looking for small molecules that prevent the loss of the protein p27. Loss of p27 directly correlates with tumor progression and poor prognosis in several cancers, including breast, colon and prostate. Dr. Rico-Bautista has identified three small molecules that restore normal levels of p27 in prostate cancer cells and is designing and testing similar molecules.

This year’s Fishman Fund Award winners are:

Maria C ecilia Scimia , M. D. Dr. Scimia has been working with Dr. Pilar Ruiz-Lozano to analyze ways to protect the heart against stress. The team has discovered a cell surface receptor protein that may be a promising target for new therapies. Dr. Scimia also works with Dr. Mark Mercola to better understand cellular signaling in the adult heart in cardiac regeneration.

M el a n ie Hoefer , Ph. D. Under the direction of Dr. Robert Rickert, Dr. Hoefer investigates the crosstalk between the immune system and the bone. Using different mouse models, she hopes to decipher the underlying causes and mechanisms leading to diseases affecting the joints, such as rheumatoid arthritis and osteoarthritis. Joc h en M aurer, Ph. D. Dr. Maurer studies cancer stem cell biology with Drs. Evan Snyder and Robert Oshima. He is establishing a line of breast tumor initiating cells, which will be an invaluable tool to screen for proteins or other molecules that can change the cell’s fate. The goal is to find a compound that cures breast cancer.

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The B urnham Repor t | www.burnham.org

C hih-C h eng Yang, Ph. D. Dr. Yang works in Dr. Dieter Wolf’s lab studying protein loss in prostate cancer. NKX3.1 is a prostate-specific tumor suppressor protein that is highly unstable and easily degraded during prostate cancer. Dr. Yang is working to identify the cellular pathways that degrade this protective protein and find drugs that can short-circuit those pathways to increase the amount of NKX3.1 available in cells to suppress prostate tumors.


president’s Message

The Curved Path I tend to approach things head-on. I like plans to be in place, objectives defined and projects moved forward in an orderly fashion. In some ways, this is at odds with my career as a basic research scientist. What we do in the lab rarely moves in a straight line. Sometimes the research may choose a direction we never anticipated. However, I have found that the curved path can provide the most profound insights. I have spent a large part of my career studying the mechanisms behind apoptosis or programmed cell death. When I began this work, the obvious hope was that our research would lead to new cancer treatments. Though it has taken many years, these hopes have come closer to fruition in potential new cancer drugs like Genasense and ABT 236, which work to defeat certain anti-cell death proteins and make it easier for chemotherapy and radiation to kill

John C. Reed, M.D., Ph.D. President and CEO Professor and Donald Bren Presidential Chair

cancer cells (see article page 1). However, using the knowledge we have acquired from apoptosis research to defeat cancer is only one of many possible applications. Cell death can be a good or bad thing, depending on the circumstances. For a person who is experiencing a heart attack or stroke or who has a neurodegenerative condition, the ability to keep cells alive could be enormously beneficial. The switch works both ways. Having a basic understanding of the mechanisms that underlie programmed cell death canReed help us by keeping good cells alive, as well as killing bad cells. 15. John essay But our understanding of apoptosis has led to advances far beyond the study of human health. In equatorial Africa, plant fungi periodically wipe out banana crops, eliminating one of the region’s main food sources. The William and Melinda Gates Foundation has sponsored field tests of a genetically engineered banana crop that could help solve this enormous problem. The engineered banana plant contains technology derived from apoptosis research, in which an anti-death gene from cancer cells is used to protect plants against fungi and other pathogens. If the current field tests are successful, this engineered crop could ease hunger throughout the world. One of the great benefits of basic research at Burnham is that it embraces the accidental

Having a basic

understanding of the mechanisms that underlie programmed cell death can help us by keeping good cells alive, as well as killing bad cells.

discovery. Quite often in the lab, we look for one thing but find another. Sometimes the unintentional discovery turns out to be more important than what we intended to find. Many words have been used to describe this circumstance: serendipity, happenstance, luck. Yet, we have seen these excellent, though often unintended, results happen often. That is why we are in the business of discovery research. Though we don’t know exactly what we may find, we do know we are better off for having that knowledge.

w w w. b u rn h a m . o rg | T h e Bu r n h a m Re p o r t

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Philanthropy

Partners

in Science:

Jones and Dr. Amy Howes Jeanne

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Author Jeanne Jones has seen enough of cancer to last a lifetime. A breast cancer survivor herself, Jones watched her sister lose her battle against ovarian cancer. She knows that more needs to be done and, at the 2007 Burnham Gala, made a gift to support postdoctoral fellow Dr. Amy Howes’ work on cancer spheroids. This research may lead to new, more effective cancer therapies with fewer side effects.

“I am so impressed with the discovery program at Burnham,” says Jones. “I saw the battle my sister went through for two years with her cancer. I know we can do better.”

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PAID The Burnham Institute


Winter 2008