Fall 2012

S A N F O R D - B U R N H A M

M E D I C A L

R E S E A R C H

I N S T I T U T E

More Than the Sum of Our Parts Partnering for Discovery Collaboration Accelerates Progress

VOLUME 2 NUMBER 4 | FALL 2012

FOUNDERS

Dr. William H. and Lillian Fishman HONORARY TRUSTEES

Roberta and Malin Burnham Joe Lewis Conrad T. Prebys T. Denny Sanford TRUSTEES AND OFFICERS

M. Wainwright Fishburn, Jr.

A Message from Malin Burnham 1 More than the Sum of Our Parts 2 Partnering for Discovery 5 Thank You: A Generous Gift from the Viterbi Family 6 Robert Rickert: Collaboration Accelerates Progress 7 Recent Events 8 Upcoming Events 9 Realizing a Vision 10

CHAIRMAN

Community Outreach 12

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

Partners in Science Back Cover

CHIEF EXECUTIVE OFFICER PROFESSOR AND DONALD BREN CHIEF EXECUTIVE CHAIR

Kristiina Vuori, M.D., Ph.D. PRESIDENT PROFESSOR AND PAULINE AND STANLEY FOSTER PRESIDENTIAL CHAIR JEANNE AND GARY HERBERGER LEADERSHIP CHAIR IN CANCER RESEARCH DIRECTOR, NCI-DESIGNATED CANCER CENTER

S A N F O R D - B U R N H A M

M E D I C A L

R E S E A R C H

I N S T I T U T E

Ann Carollo

VICE PRESIDENT, COMMUNICATIONS

Gary F. Raisl, M.B.A., Ed.D.

Deborah Robison

EXECUTIVE VICE PRESIDENT CHIEF ADMINISTRATIVE OFFICER CHIEF FINANCIAL OFFICER TREASURER

PORTAL EDITOR

Kristina Meek, M.A. CONTRIBUTORS

Margaret M. Dunbar, J.D.

Patrick Bartosch Heather Buschman, Ph.D.

SECRETARY

Lorenzo Berho Shehan Dissanayake, Ph.D. Daniel J. Epstein Pauline M. Foster Alan A. Gleicher Jeanne L. Herberger, Ph.D. Brent Jacobs James E. Jardon II Robert J. Lauer Stuart Lipton, M.D., Ph.D. J. Bernard Machen, D.D.S., Ph.D. Nicolas C. Nierenberg Douglas Obenshain Peter Preuss Duane J. Roth Jan Tuttleman, Ph.D., M.B.A. Andrew J. Viterbi, Ph.D. Allen R. Weiss Gayle E. Wilson EX-OFFICIO

Todd Golub, M.D.

SCIENTIFIC ADVISORY BOARD CHAIRMAN

SENIOR VICE PRESIDENT, EXTERNAL RELATIONS

DESIGN

Creative Fusion

More Than the Sum of Our Parts Partnering for Discovery Collaboration Accelerates Progress

VOLUME 2 NUMBER 4 | FALL 2012

ON THE COVER

Sanford-Burnham’s scientists work collaboratively across five research centers to accelerate discovery. Clockwise from top: Drs. Rolf Bodmer and Malene Hansen, Drs. Dan Kelly, Ling Lai, and Teresa Leone, Dr. Maria Diaz-Meco, Drs. Hudson Freeze and Lars Bode, Drs. Zhen Jiang and Zhenwei Gong.

www.sanfordburnham.org

Toll-free: 1-877-454-5702

Sanford-Burnham Medical Research Institute

10901 North Torrey Pines Road, La Jolla, CA 92037 • 858-646-3100

Sanford-Burnham Medical Research Institute at Lake Nona 6400 Sanger Road, Orlando, FL 32827 • 407-745-2000

A Message from

Malin Burnham I have had the pleasure of meeting many of you, the friends and donors to SanfordBurnham, at various events and activities hosted by the Institute. What always strikes me is your interest in being part of something larger than yourselves.

Although you and I are not the ones in the laboratories making the discoveries, please know that you can still be a part of something great at Sanford-Burnham.

Dr. Reed leads a workforce of scientists who maximize their potential by taking a multi-disciplinary approach to research.

They are empowered to collaborate. Basic research offers opportunities for scientists to reach across laboratories and across research centers to share their findings.

As you will read in the following pages, discoveries often lead in new and unexpected directions. While a for-profit business might curtail the exploration of an idea that doesn’t lead where they want it to, SanfordBurnham is positioned to pursue it.

Collaboration is the future of this world.

In order to get the best things done, we have to work in partnerships, in networks.

We have to collaborate with people from all walks of life. Then, one and one can literally add up to more than two.

Thank you for joining me in supporting Sanford-Burnham.

– Malin Burnham

SANFORD-BURNHAM BENEFACTOR AND HONORARY TRUSTEE

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More than the

Sum of Our Parts Medical science changes and evolves all the time; that dynamic quality is likely what excites you about Sanford-Burnham.

Sometimes a scientist makes a discovery that reveals even more that he or she hoped. At Sanford-Burnham, scientists follow leads to realize the full potential of their discoveries.

Working in five distinct but overlapping research centers, Sanford-Burnham’s scientists represent a wide range of expertise. Each one brings a valuable part—his or her unique knowledge—to a thriving whole. Here, within our collaborative environment, these component parts are further enabled with myriad technological resources to become something greater.

A researcher studying one disease may unearth a potential treatment for another. Thanks to Sanford-Burnham’s people, resources, and culture, that researcher has room to follow the lead and has the best chance of finding a cure. Here are just a few examples of research that has led in a new and exciting direction thanks to an environment that is more than the sum of its parts.

In seeking treatments for diabetes, Dr. Fred Levine, director of our Sanford Children’s Health Research Center, may have found a new way to fight cancer, too.

Using the drug discovery capabilities in our Conrad Prebys Center for Chemical Genomics, he and his team found a compound called BIM5078 that will bind to HNF4α, a protein that plays a role in insulin production. This feat—once thought impossible with regard to this particular protein—could be the first step toward creating a new medicine to help treat diabetes.

Even more exciting, Dr. Levine’s team found that BIM5078 also selectively kills a number of different types of cancer cells grown in the lab. These findings open up a variety of pharmacological possibilities.

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Dr. Gregory Roth

Dr. John Reed, CEO and professor in our National Cancer Institute-designated Cancer Center, based in La Jolla, and Dr. Gregory Roth in the Diabetes and Obesity Research Center in Lake Nona, collaborated not only across disciplines but across the country. Together they led a research team that discovered small molecules that curb pro-inflammatory responses of the immune system. Given that the immune system becomes overactive in certain diseases such as Crohn’s, the newly discovered compounds show promise as the basis for new medications for these conditions.

Dr. Barbara Ranscht

Dr. Barbara Ranscht in our NCI-designated Cancer Center discovered T-cadherin, a protein that regulates cell movement and growth. For many years she studied how this protein functions in the brain and nervous system. A conversation with her friend and colleague Dr. Pilar Ruiz-Lozano, a heart researcher in our Del E. Webb Neuroscience, Aging, and Stem Cell Research Center, led to an experiment for testing T-cadherin’s role in protecting the heart. Together with their teams, the pair successfully demonstrated the link between T-cadherin and heart disease, shedding new light on a killer of millions.

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Dr. José Luis Millán began working on an enzyme known as alkaline phosphatase when he was a graduate student in the lab of Dr. William Fishman, co-founder of the Institute. They were interested in this enzyme because it’s elevated in some forms of cancer.

We now know that alkaline phosphatase is important in other diseases, too. Alkaline phosphatase deficiency in children prevents their bones from forming properly, causing severe disability and death. A drug based on Dr. Millán’s work was tested in children with this condition. Children who would have died have not only been saved, they’ve even gained the ability to walk, jump, and play.

Dr. Millán went on to develop drugs that inhibit alkaline phosphatase, since it turns out that having too much leads to atherosclerosis (hardening of the arteries). He hopes these drugs will benefit children with a severe, early onset form of atherosclerosis. If trials go well, the drug could benefit many adults as well.

Immunology, the study of the immune system, lies at the heart of our Infectious and Inflammatory Disease Center. Science is just beginning to appreciate the significance of cross-talk between cancer cells and the immune system. Dr. Carl Ware, the Center’s director, has made a finding that may eventually speed the recovery of cancer patients who receive bone marrow transplants. Follow the future work of Dr. Ware and others in the Center to learn what they’re doing to fight cancer.

Want to Discover More?

Read about all of these studies and more like them on our blog at beaker.sanfordburnham.org.

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Partnering for Discovery The story of Dr. Yu Yamaguchi, professor in our Sanford Children’s Health Research Center, and Sarah Ziegler, the mother of a boy with a rare bone disease, has been unfolding for almost 10 years. You may have read some of the related posts on our blog, Beaker. Their story clearly illustrates how the synergy among scientists and patient advocates can lead to exciting developments.

In 2003, Dr. Yamaguchi was conducting research focused on the function of certain genes affecting the brain, when he received a call from Sarah Ziegler. Sarah’s son, Robert, suffers from multiple hereditary exotoses (MHE), which causes multiple growths on the bones that cause pain, disfigurement, and stunted growth. At the moment, the only treatment is surgery to remove the growths; there is no cure. As it turned out, MHE is caused by defects in the very genes Dr. Yamaguchi was studying.

As Robert endured many surgeries, Sarah educated herself about MHE and bones. She co-founded the MHE Research Foundation, based in Brooklyn, New York. Through her research, she heard about Dr. Yamaguchi and had a feeling his research could impact MHE. In a letter to Dr. Yamaguchi, Sarah recalled that first phone call: “When I picked up the phone, you graciously took the

time to speak with me in detail…the energy in your voice concerning all of the possibilities was truly profound.” As the relationship unfolded, Dr. Yamaguchi became increasingly interested in MHE and helped to organize the foundation’s annual conference.

For his contribution to MHE research, they presented him with their Humanitarian Scientific Achievement Award in 2007.

MHE research has long been hampered by the lack of a good model that would answer questions about the underlying cause and allow scientists to test new treatments. In 2010, Dr. Yamaguchi and his collaborators unveiled a mouse model that does just that in the journal Proceedings of the National Academy of Sciences.

Sarah was understandably excited by the news. “This research is profoundly important,” she said. “With this model, researchers can

Dr. Yu Yamaguchi with Sarah Ziegler’s son, Robert

start looking for a cure.”

One of Sarah’s greatest frustrations was that most medical specialists only saw one part of Robert’s disease. She knew from her experience with MHE patients that the disease affects more than bones. These kids have social problems, too. She discussed this idea with Dr. Yamaguchi, setting his research on a new course that led to his team’s latest finding.

Recently, Dr. Yamaguchi and his team used that mouse model to investigate cognitive function. Sarah had noticed that many children with MHE displayed characteristics that fall along the autism spectrum. Dr. Yamaguchi and his team began to study Continued on Page 11

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Thank You

A Generous Gift from the Viterbi Family

Dr. Evan Snyder

Prominent San Diego philanthropist and businessman Andrew Viterbi, his wife Erna, and their family recently presented Sanford-Burnham with a $1 million gift to establish the Neuroscience Research Initiative.

Dr. John C. Reed, Sanford-Burnham CEO, and Dr. Evan Y. Snyder, director of the Institute’s Stem Cell and Regenerative Biology Program, will lead the research. Combining expertise in cellular behavior and innovative stem cell research, their collaboration demonstrates Sanford-Burnham’s crossdisciplinary approach to medical science.

The two-year initiative will employ “disease-in-a-dish” technology, in which

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stem cells are used to generate large collections of a particular cell type in the laboratory—certain types of brain cells, in this case. Our researchers will then use these cell-based models to better understand the underlying causes of disease.

“Disease-in-a-dish research is opening new doors for translational medicine,” said Dr. Reed. “A brilliant entrepreneur like Andrew Viterbi can appreciate its enormous potential. We are truly grateful that he has chosen to invest in our research.”

“Erna and I have been actively involved with the Institute for nearly three decades,” said Dr. Viterbi. “I was invited to join the board by [institute co-founder] Dr. William Fishman in 1984, and I am still a member. Erna has long been involved with the Fishman Fund for the recognition of postdoctoral researchers. Over the years we’ve been impressed both by the bright minds that call this place home and by the Institute’s culture that is consciously designed to foster ingenuity and collaboration. Under the leadership of Dr. Reed, Sanford-Burnham has become the place to embark on a project such as this.”

Dr. Viterbi is well-known as the co-founder of Qualcomm, Inc. and is internationally recognized in the field of digital communication. He is a recipient of the National Medal of Science, the country’s highest honor for scientific achievement.

We sincerely thank the Viterbi family for their generosity.

TALKING WITH A SCIENTIST

Robert Rickert:

Collaboration Accelerates Progress Dr. Robert Rickert

When you finally find a solution to something, say a website with valuable travel tips or a great physician, you probably tell some friends about it. You want others to benefit from your discovery.

Scientists at Sanford-Burnham, working in close collaboration, take the same approach by sharing scientific tools. By collaborating, they accelerate progress toward treating human disease.

Dr. Robert Rickert, director of the Inflammatory Diseases Program at SanfordBurnham, is an immunologist. In his studies of the immune system, he focuses on a type of white blood cells known as B cells. B cells respond to a wide range of pathogens by producing antibodies. They are basic building blocks of the immune system, fascinating for their own sake, but holding boundless potential new knowledge for medical science. “Our laboratory focuses on basic mechanisms of B cell development and activation, but we’ve also been fortunate to be able to use what we’ve learned as a first step toward gaining insight into disease mechanisms,” says Dr. Rickert.

The Rickert laboratory studies the genetics of both normal and abnormal B cells. B cells usually help keep us healthy, but if they acquire certain gene mutations and reproduce too rapidly, they can give rise to leukemia or lymphoma. “When we discover

a new gene that we think is important for B cells,” Dr. Rickert explains, “the first thing we do is to see if it happens to be under or overproduced or mutated in a known B cell-related disease. Often, however, the genes we look at turn out to be interesting for other cell types and other processes.”

At Sanford-Burnham, new findings don’t just benefit the lab where they’re made.

“One of the main techniques in our lab is gene targeting,” Dr. Rickert says, “where we can actually inactivate particular genes or introduce tailored mutations. In that case, I usually find a colleague here who has expertise with those other cell types, and see if they would be interested in this particular model system.”

A mouse model of a particular gene mutation, developed by Dr. Rickert’s lab, is currently of interest to three different researchers at the Institute. The gene in question, called PDK1, is absolutely essential to B cells, but is involved in a variety of molecular processes. Dr. Rickert realized that Dr. Ze’ev Ronai, with whom he sometimes collaborates in Sanford-Burnham’s NCIContinued on Page 11

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Recent RECENT EVENTS

Bring It!

The audience cheers for the teams competing in the final round of the Bring It! challenges.

Our fourth annual Bring It! event was held April 27 in San Diego to raise money for stem cell research. More than 200 guests packed the room and competed to win the title of Bring It! 2012 champion.

Event chairs Terry and Stath Karras are greeted by celebrity impersonators outside Bring It!

President’s Circle

In May, we invited members of the SanfordBurnham President’s Circle to a special discussion, What Will it Take to Cure Cancer?, at the San Diego Natural History Museum. Dr. Mary Walshok (white jacket) moderated a panel that included (from L to R) Dr. Robert Abraham, Dr. Erkki Ruoslahti, Dr. Anna Barker, and Dr. Ron Andrews. On the far right are Sanford-Burnham President Dr. Kristiina Vuori and CEO Dr. John C. Reed.

Special Event

In April, Sanford-Burnham hosted former Florida Governor Jeb Bush at a reception for community leaders in Miami. He spoke about the progress of Florida’s emerging life science research clusters across the state.

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Upcoming UPCOMING EVENTS

October 3

Stem Cell Awareness Day

Join us in observing Stem Cell Awareness Day, sponsored by the California Institute for Regenerative Medicine. Details will be announced soon.

Visit www.stemcellday.com

November 17

Marching Towards a Cure You’re invited to an evening of music, merriment, and classic Americana at our 2012 gala, Marching Towards a Cure, inspired by the classic Broadway musical, The Music Man. Event chairs Conrad Prebys and Debbie Turner will lead the band, along with co-chairs Sheila and Jeffrey Lipinsky, Blair Blum and Jim Sexton. Enjoy cocktails, dinner, and a live performance by Alet and Andy Taylor, from the cast of the Tony Award-winning musical Once.

Visit www.sanfordburnham.org/gala

October 11

Fishman Fund Awards Ceremony & Reception Join us in Fishman Auditorium at our La Jolla campus to congratulate five outstanding young postdoctoral researchers who will be receiving this year’s Fishman Fund Awards, named for the Institute’s founders, Dr. William and Mrs. Lillian Fishman.

The ceremony begins at 5:30 p.m., followed immediately by a reception.

Visit www.sanfordburnham.org/events

October 7-9

The Atlantic Meets the Pacific

Sanford-Burnham is proud to be taking part, once again, in The Atlantic Meets the Pacific, a forum devoted to the future of media, energy, and health, presented

by UC San Diego and The Atlantic magazine. A series of headline interviews and riveting panel discussions will complement off-site visits to research centers, cultural landmarks, and laboratories. Participants will have the option to tour our La Jolla campus for behind-the-scenes exposure to new technologies and scientific research.

Learn more at www.atlanticmeetspacific.com. www.sanfordburnham.org | PORTAL

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Realizing a Vision This past spring, Sanford-Burnham lost a trusted friend, supporter, and trustee, Arthur Brody.

A highly respected philanthropist and president of the Sophie & Arthur Brody Foundation, Mr. Brody was a visionary man who believed in the power of scientific research to cure disease.

He contributed generously to the Institute over the course of 20 years, supporting our Stem Cell Research Center, prostate cancer research, and the laboratory of Dr. Stuart A. Lipton, director of our Del E. Webb Neuroscience, Aging and Stem Cell Research Center. He also invested in young scientists through gifts to the Fishman Fund.

Mr. Brody made his largest single contribution in 2010, when he made a generous gift to create the Art Brody Innovation Fund. These resources support promising research that might otherwise be stalled due to lack of funding.

The Art Brody Innovation Fund supports efforts to translate basic research discoveries into new medicines, a goal that is central

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to Sanford-Burnham’s mission. It can take many years and great expense to advance scientific discoveries into treatments or cures. The future of drug development depends on investment in translation.

“As researchers, we are acutely aware of the importance of philanthropic support, particularly in these difficult times in which there is a downturn in NIH funding,” Dr. Lipton said. “It takes a visionary person like Art Brody to realize the long-term value, both financially and in lives saved, of an investment in medical research. We are fortunate to have known him both as a close friend and as a supporter. He will be truly missed.”

If you would like to help us move our discoveries closer to treatments for patients, please consider making a gift to the Art Brody Innovation Fund. You may use the enclosed envelope, call us at (877)454-5702, or make a secure online contribution at sanfordburnham. org. Help us honor Art Brody and realize his vision for the cures of tomorrow.

Continued from Page 4

Partnering for Discovery the behavior of the mice and found that the mice show symptoms that meet the three defining characteristics of autism: social impairment, language deficits, and repetitive behavior. The study, published in March in the Proceedings of the National Academy of Sciences, also defines the molecular and physiological basis of this behavior, pinpointing the amygdala as the region of the brain causing autistic symptoms.

Not all autistic children have MHE, nor are all MHE children autistic. But, according to Yamaguchi, there is evidence that some people who are autistic might have similar defects in heparan sulfate, the sugar chain that’s defective in MHE. A story about this study appeared in The Scientist in June.

Sarah also played a role, along with Dr. Yamaguchi and Dr. Hudson Freeze, in launching Sanford-Burnham’s annual Rare Disease Symposium, first held in 2010. Each year, young rare disease

patients and their parents—people just like Sarah—attend the event to hear about new research developments. They learn something, but they also provide inspiration and hope to the researchers.

“I can’t emphasize enough how much it helped that the parents of kids with MHE got involved and supported this research,” Dr. Yamaguchi said.

In her letter to Dr. Yamaguchi, Sarah continued, “You took up this massive challenge with a vigor that amazed me.

Each and every day since, you and your team of researchers have worked to discover the etiology of MHE by developing the new mouse models for this disease. These new models have borne great fruit!”

This story demonstrates that collaboration doesn’t just happen among scientists, but also between scientists and people like you.

Read more on our blog, Beaker, at beaker.sanfordburnham.org.

Continued from Page 7

Collaboration Accelerates Progress designated Cancer Center, might benefit from the same mouse model. Dr. Ronai is interested in the same gene—but in melanoma cells.

Dr. Maurizio Pellecchia, a professor in the Infectious Diseases Program has developed inhibitors that target the protein this gene produces, and Dr. Linda Bradley, a professor in the Inflammatory Diseases Program who studies Type 1 (juvenile) diabetes, is also developing an interest in the model. Each researcher’s unique skill set allows him or her to see different potential in this one model.

“The scope can be fairly broad, when we’re

all interested in this one gene, but in many different contexts,” says Dr. Rickert.

“We have our interest, then Dr. Ronai focuses on a very different cell type, Dr. Bradley, a T-cell immunologist, investigates autoimmune diseases, and then Dr. Pellecchia brings his biochemical structural expertise.”

Dr. Rickert’s inclusive approach extends to budding scientists as well. As associate dean of Sanford-Burnham’s graduate program, he counts a significant number of students among his lab members. “It’s rewarding for me to see how they

mature as scientists and become creative, independent thinkers.”

Engaging in basic medical research requires long-term thinking, dedication, and enthusiasm.

“We’re always conscious of the potential impact our research could have down the line, even when it’s difficult or impossible to envision that impact. Despite the challenges, whether you’re an undergraduate, graduate, postdoc, or at whatever stage of your career, every day there is the potential to reveal something exciting and novel. To do what we do is really a privilege.”

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Community Outreach Here at Sanford-Burnham, we work continuously to reach out to young people aspiring to careers in science, through internships and other programs, throughout the year—but summer is an especially busy time.

In June, Sanford-Burnham at Lake Nona in Orlando welcomed five students from nearby high schools and colleges, including Trinity Preparatory School, Seminole High School, the University of Central Florida, Rollins College, and the University of Miami.

The United Negro College Fund (UNCF), Sanford-Burnham, and law firm Akerman Senterfitt recently launched the STEM Pipeline Program aimed at providing opportunities for African-Americans and other minorities to learn more about science, technology, engineering, and math, and to explore careers in these fields. The program awarded a four-summer internship to a high school student who aspires to a life science career.

Also in Lake Nona, 40 students participated in a Junior Achievement summer program to learn about medical research career paths. Junior Achievement inspires young people by helping them make the connection between what they learn in school and what they will need to know for the future. Drs. George Kyriazis and Daniela Divlianska explained what led them to choose careers in science.

A large number of interns spent time at the La Jolla campus this summer as well. Among them were 11 promising high school students from The Preuss School UCSD, recently named the #1 Transformative High School in the nation by Newsweek. This annual program offers students the opportunity to work in a different laboratory each day for four days.

Dr. Daniel Kelly, scientific director of Sanford-Burnham at Lake Nona, spoke to the Orange County Commission about the Institute’s commitment to help train students to become the scientists of tomorrow. Mayor Teresa Jacobs and the commissioners were glad to hear about the Institute’s progress in helping develop Orlando’s life science community.

Community groups often tour our campuses. Some recent visitors to our La Jolla location include the board of directors of the Rancho Santa Fe Foundation, a group from National Defense University in Washington, D.C., and Women of Wonder, hosted by Sanford-Burnham trustee Jeanne Herberger.

Opposite Page Top: Interns Scott Robertson and Marissa Roth with Dr. Sheila Collins (center) at Lake Nona.

Middle Left: Christy Wilson and Candace Humber from the Rancho Santa Fe Foundation. Middle Right: Drs. Layton Smith (right) and Cedric Bright (left) discuss the STEM Pipeline Program.

Bottom: Interns from the Preuss School UCSD.

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PARTNERS IN SCIENCE

Daniel J. Epstein and Dr. Ze’ev Ronai

Daniel J. Epstein closely follows the work of Dr. Ze’ev Ronai, associate director of SanfordBurnham’s National Cancer Institute-designated Cancer Center. Mr. Epstein, founder of the ConAm Group of Companies and Sanford-Burnham trustee, visited Dr. Ronai’s lab to hear about some of his ongoing work. Cancer has affected Mr. Epstein’s family, prompting him to donate in pursuit of treatments and cures.