Join Us in Transforming Medicine

Eli and EdythE Broad CirM CEntEr FOr regenerAtive MeDiCine AnD SteM CeLL reSeArCh At USC

Produced by the USC Health Sciences Public Relations and Marketing office for the Keck School of Medicine Development Office. ©2008

writing: carrie st. michel design: leslie baker graphic design photgraphy: bill youngblood

Fish, fireflies, and feathers are helping

to forge the future of medicine.

Fish, fireflies, and feathers are helping

to forge the future of medicine.

More accurately, fish, fireflies, and feathers in the highly skilled hands of scientists at the University of Southern California’s Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research — are forging the future of medicine. A transformation is unquestionably underway, and it’s being fueled by the fact that these leading-edge researchers — quite simply — see things differently.

A fish, specifically a zebra fish, isn’t merely a striped freshwater inhabitant. For one scientist, this cold-water creature is instead serving as a link — by studying its facial skeletal development — to uncovering what processes are responsible for human facial birth defects.

To the average eye, a firefly is likely little more than a fanciful insect that illuminates the night sky. Not so to a researcher who discovered that the gene from a firefly can illuminate stem cells as they settle in bone marrow and, along the way, shed light on how to better perform often-life-saving bone-marrow transplants.

A feather peeking through a down comforter generally goes unnoticed, unless you’re a stem cell scientist who sees feathers as something of a Rosetta stone. Feathers possess unusually robust regenerative power, and by studying their stem cells, another renowned researcher is mining morphogenesis — how cells are assembled into functional forms. Armed with this information, focus can then turn to uncovering stem cells’ regenerative abilities — from healing wounds to conceivably re-growing limbs.

Stem cell scientists at USC’s Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research clearly see the world differently and, as a result, their unique vision is transforming the world of medicine.

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Left: Microscopic image of a zone of stem cells from an adult human colon.

The allure of embryonic stem cells is rooted in their virtually unlimited developmental potential to form any cell in the human body. Stem cells are thus a window into the normal development of cells, as well as into the mechanisms at work when cell development deviates, such as in the case of cancer. With stem cells, scientists also have access to an essentially unlimited supply of specific cell types for basic research and transplantation therapies designed to one day treat a wide spectrum of diseases. Stem cells’ regenerative capabilities additionally point to the distinct possibility of employing replacement cells to repair damaged skin, heart muscles, livers, lungs, and retinas — to cite just a few of the many on-the-horizon breakthroughs. Now, there is even the possibilty of making stem cell lines from adult tissue with all the capabilities of embryonic stem cells, a highly exciting line of research being pursued by center investigators.

Consider this sampling of promising horizons that researchers at the University of Southern California’s Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research are currently pursuing:

8 Cancer Center researchers are gathering increasing evidence that certain stem cells are predisposed to becoming cancer cells — a finding that is greatly accelerating understanding of this deadly disease.

8 Cardiology Significant strides are being made by center scientists who are studying ways to trans-form stem cells into heart muscle cells capable of repairing myocardial infarction (heart attack) damage.

For nearly a decade now, human embryonic stem

cells have captured the minds and microscopes

of scientists worldwide.

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8 Liver Disease Center scientists are working to identify cells capable of repairing liver damage caused by disorders such as Hepatitis C infection, a worldwide epidemic which currently accounts for most of the unfulfilled demand for liver transplants.

8 Hematology and Oncology Center scientists are studying how blood is formed from primitive stem cells found in the bone marrow. This research will help to develop future sources of cells or for use in transplantation to treat leukemias and other disorders. They also study cancer stem cells, which many believe are the most important targets for new therapies designed to cure rather than simply alleviate tumors.

8 Ophthalmology Reversing damage from devastating eye diseases such as macular degeneration — the

most common cause of blindness in Americans over 60 — is the goal of center researchers investigating the

therapeutic impact of retinal pigment epithelial cells-critical partners of the light sensing cells in the back of

the eye-derived from human embryonic stem cells.

With each passing day, stem cell scientists at USC’s Eli and Edythe Broad Center for Regenerative Medicine

and Stem Cell Research are inching closer to this hopeful horizon.

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Liver precursor cells in a human embryonic stem cell culture.

Recognizing that Baby Boomers were living longer and would need money in retirement rather than life insurance policies, he transformed a traditional death benefits company into a retirement savings company and pioneered the use of annuities and other financial services products. That’s vision.

Recognizing the potential of stem cell research to usher in an era of life-saving discoveries, he donated $30 million to seed the building of what will be one of Southern California’s largest stem-cell-research centers. That’s vision.

And that vision belongs to Eli Broad, renowned corporate leader who built two Fortune 500 companies from the ground up — KB Home (formerly Kaufman and Broad Home Corporation) and SunAmerica Inc. Broad’s enormously generous donation — made with his wife Edythe — is propelling the Keck School of Medicine of USC’s stem cell initiative to a new level of excellence and achievement. As USC President Steven B. Sample pointed out, the Broads’ gift “will enhance the quality of life not only for the people of Southern California, but for people around the world.”

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Philanthropists Eli and Edythe Broad

Armed with only meager startup capital, he helped

revolutionize the home-building industry by popular-

izing the concept of affordable, tract homes tucked

away in suburban neighborhoods. That’s vision.

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Looking toward the future, Eli Broad said, “This will hopefully be the anchor of a new biomedical corridor in the region, where the nation’s most cutting-edge research is conducted by some of the brightest minds in science.” The “anchor” to which Broad refers is the actual building that will be constructed — the Eli and Edythe Broad CIRM Center for Regenerative Medicine and Stem Cell Research at USC — and the research program it will house — the University of Southern California’s Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research.

Summing up the Broads’ crucial contribution, Sample observed: “For many years, the Broads have been the driving force behind programs that promote health and well-being, enhance cultural and educational opportunities, and support urban and economic revitalization. We are very fortunate that Edythe and Eli have the vision to see what needs to be done, the generosity to make it possible, and the will to make it a reality.”

With the 2006 recruitment of Martin Pera, Ph.D.,

USC’s Eli and Edythe Broad Center for Regenerative

Medicine and Stem Cell Research solidified its

reputation for leading-edge, stem cell innovation.

An internationally recognized pioneer in the development of embryonic stem cells, Pera — who now serves as the center’s director — was among the first worldwide to propose developing embryonic stem cells from human embryos not used for in vitro fertilization. Originally a cancer researcher, Pera — while working at Oxford University more than two decades ago — discovered stem cells in tissue taken from patients with testicular tumors.

“I had the good fortune to be involved in the founding of human embryonic stem cell research, and as a consequence of this role, I feel a special responsibility to see this new science realize its promise,” Pera explains.

Pera, whose commitment to unlocking stem cell solutions has taken him around the world, (he most recently served as the director of Embryonic Stem Cell Research at the Australian Stem Cell Centre and a research professor at Monash University), has a clear vision for the center at USC: “We must focus on building for the future by firmly establishing stem cell science as the foundation for regenerative medicine.” Pera goes on to stress the importance of working closely with USC clinicians to ensure that discoveries made in the lab are translated to the bedside as quickly as possible: “We are turning discoveries in stem cell biology and tissue repair into platform technologies that we develop into patient treatments.”

Looking ahead, Pera notes, “Our center is already considered a leader in stem cell research, and we’re making tremendous strides toward cementing that position. Our recruitment efforts have been extremely successful, and the research underway here is exciting and very promising. We’re focusing on building for the future, and we definitely have a strong foundation on which to build.”

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Left: Martin Pera, Ph.D., in his laboratory.

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Such synergy already abounds at the University of Southern California’s Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, where Center Director Dr. Martin Pera has been recruiting leading stem cell researchers — from around the world — at a record pace. In fact, during the last year these standout scientists have joined the center’s faculty:

Gregor B. Adams, Ph.D. Assistant Professor of Cell and Neurobiology — Dr. Adams comes from the laboratory of Dr. David Scadden at Massachusetts General Hospital, Harvard Medical School. His research focuses on the hematopoietic stem cell niche in bone marrow, and he discovered how cells in that tissue help to direct blood stem cell growth and differentiation.

Gage D. Crump, Ph.D. Assistant Professor of Cell and Neurobiology — Formerly of the Kimmel labora-tory at the University of Oregon, Dr. Crump studies zebra fish to better understand local tissue-tissue interactions that control skeletal differentiation and morphogenesis in vivo.

Michael Kahn, Ph.D. Provost’s Professor of Medicine and Pharmacy — Previously the scientific director at the Institute for Chemical Genomics and a professor at the University of Washington, Dr. Kahn is a leader in the emerging field of chemical genomics. He has discovered new drugs that modulate a key pathway in stem cell regulation and cancer growth.

While successful enterprises have many moving parts,

all share a common characteristic: they are propelled

by dedicated, talented professionals whose combined

efforts are greater than the sum of their individual efforts.

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Krzysztof Kobielak, M.D., Ph.D. Assistant Professor of Pathology — Dr. Kobielak was with the laboratory of Elaine Fuchs of The Rockefeller University. He studies bone morphogenetic protein and its role in stem cell development into hair or skin cells, work which is advancing our under-standing of wound healing.

Wange Lu, Ph.D. Assistant Professor of Biochemistry and Molecular Biology — Dr. Lu came to the center from the laboratory of Nobel laureate David Baltimore at the California Institute of Technology. Lu’s research focus is Ryk-mediated Wnt signaling and its functions in neural stem cell proliferation and differentiation. By exploring this novel pathway, Lu is unlocking new approaches to treating neural disorders.

Francesca Mariani, Ph.D. Assistant Professor of Cell and Neurobiology — Dr. Mariani is working to more fully understand the molecular control of normal embryonic development and homeostasis in adults as tissues develop in three dimensions. This fundamental research may one day help guide the path towards rebuilding these complex structures from cells.

Qi-Long Ying, Ph.D. Assistant Professor of Cell and Neurobiology — Dr. Qi-Long Ying came from the Institute for Stem Cell Research at the University of Edinburgh, United Kingdom. His research focuses on understanding how embryonic stem cells decide whether to self-renew or to differentiate. Ying’s work is critical to future applications of embryonic stem cells in research and medicine.

Researchers working in Dr. Martin Pera’s laboratory.

Given the promise of stem cell research, it’s essential

that discoveries made in the lab are translated to

patients’ bedsides as quickly as possible, where they

potentially can make a life-saving difference.

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Guided by this goal, the University of Southern California’s Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research recently spearheaded efforts to set stem cell research on a fast track fueled by collaboration. Specifically, Center Director Martin Pera played a pivotal role in creating the Southern California Stem Cell Scientific Collaboration (SC3).

Through SC3, center scientists are now working collaboratively with USC colleagues at Childrens Hospital Los Angeles and other colleagues at the California Institute of Technology, City of Hope, the House Ear Institute, and the University of California, Santa Barbara.

This standout consortium is collectively directing its stem cell research efforts toward restoring function in the eyes, ears, pancreas, and heart, as well as on reversing macular degeneration and arresting diabetes. SC3 scientists additionally are targeting the development of novel platforms inimaging, bioengineering, and nanotechnology that can then be applied to stem cell initiatives.

While the world of scientific research can be a competitive arena, USC and its sister SC3 institutions recognized the urgent need for collaboration. SC3’s deep bench of talent is virtually without rival nationwide; the prospect of helping millions who suffer from a broad spectrum of debilitating diseases thus moves ever closer to becoming a reality.

Left: The west façade utilizes glass fins to reduce the glare of the late-afternoon sun. The center will also serve as a backdrop to a beautifully landscaped courtyard featuring outdoor seating and an open lawn.

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CIRM came to be in 2004 when Golden State residents cast enough votes to pass Proposition 71. By so doing, California’s citizenry gave the green light for the state to sell $3 billion in general obligation bonds to provide funding — over 10 years — to support homegrown stem cell research. CIRM is led by President Alan Trounson, Ph.D., and Robert Klein, J.D., chair of the CIRM Governing Board.

In fact, as of August 2008, USC researchers had received $60 million in stem cell grants from CIRM, ranking USC third in total funds awarded to date, behind Stanford University and the University of California at San Francisco.

In May 2008, CIRM awarded USC $27 million to fund construction of the Eli and Edythe Broad CIRM Center for Regenerative Medicine and Stem Cell Research. In approving the award, the CIRM governing board applauded the project’s innovation in terms of energy efficiency and research collaboration. When completed, the five-story facility — to be located on San Pablo Street in the heart of

Aerial view of the future Eli and Edythe Broad CIRM Center for Regenerative Medicine and Stem Cell Research at USC (left). The building at right is the Zilkha Neurogenetic Institute.

From Google to green consciousness, California is

often the standard setter for our nation. Stem cell

research is no exception. The California Institute for

Regenerative Medicine (CIRM) stands as testimony

to this fact.

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USC’s Health Sciences campus — will house basic and clinical researchers working collaboratively, with stem-cell-specific core labs directly down the hall. This arrangement is both purposeful and critical to the center’s commitment to accelerate the pace of research leading to stem-cell-based therapies that can then be delivered to patients in need.

“The new center at USC will be an important addition to our campus as we create new research space for discoveries that will eventually translate to patient care,” notes Carmen A. Puliafito, M.D., M.B.A., dean of the Keck School of Medicine of USC. Center scientists will concentrate their attention on several areas for which the Keck School of Medicine of USC has already earned worldwide recognition, including liver disease, diabetes, heart disease, diseases of the eye, blood diseases, and cancer.

With construction underway for the Eli and Edythe

Broad CIRM Center for Regenerative Medicine and

Stem Cell Research at USC, a new home for new

medicine is on the horizon.

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Every day, the highly skilled stem cell scientists at the University of Southern California’s Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research are inching closer to breakthrough discoveries and laying the foundation on which the science and medicine of the future will be built. A new home for this new medicine is also on the horizon, as the Eli and Edythe Broad CIRM Center for Regenerative Medicine and Stem Cell Research at USC moves from blueprint to breaking ground.

When completed, the center will stand as a prototype and epicenter of regenerative medicine in Southern California — a facility featuring design innovation that dovetails with the world-class research being con-ducted within. Specifications include:

8 five-story building

8 80,000 square feet

8 four core laboratories

8 state-of-the-art imaging facility

8 biotechnology transfer center

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Built to accommodate 18 principal investigators and their teams, whose expertise will span basic and discovery research in stem cell biology, platform technologies, translational research, and regenerative medicine, the center’s labs are designed for maximum flexibility, allowing for different configurations based on the needs of individual researchers. Facilitating collaboration is also key, thus an entire floor of the new center will be dedicated to interdisciplinary work focusing on transplant biology, cardiovascular disease, diabetes, and other metabolic diseases. This part of the facility will guarantee access of scientists throughout USC and their collaborators in SC3 to the latest technologiesin stem cell research. Computational and clinical scientists, whose work is equally critical to a successful translational research program that brings lab-bench breakthroughs to the patient bedside, will also be located in the center.

When the Eli and Edythe Broad CIRM Center for Regenerative Medicine and Stem Cell Research at USC officially opens its doors, an era of new medicine will simultaneously open as some of the brightest minds in science today work together — under one roof — toward the shared goal of uncovering the full potential of stem cell research.

Rendering of the front view of the lobby for the new Eli and Edythe Broad CIRM Center for Regenerative Medicine and Stem Cell Research at USC.

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8 Sensing the urgency of stem cell research, Eli and Edythe Broad donated $30 million to seed our stem cell program and construct what will be one of Southern California’s largest stem-cell-research centers

8 Inching closer to breakthroughs each day, center researchers are: gathering substantive evidence that certain stem cells are predisposed to becoming cancer cells; working to reverse damage from devastating eye diseases, cardiovascular disease, and liver disease; and determining which neurological stems cells are possible vehicles for treating Parkinson’s disease.

8 Recognizing the Keck School of Medicine’s commitment to leading the stem cell charge, renowned stem cell pioneer Martin Pera, Ph.D., agreed to become the center’s founding director. Pera has since recruited several of the world’s most sought-after scientists.

8 Realizing that collaboration is central to stem cell discoveries, the center played a pivotal role in creating the Southern California Stem Cell Scientific Collaboration (SC3). Through SC3, center scientists are working with researchers at Childrens Hospital Los Angeles, California Institute of Technology, City of Hope, the House Ear Institute, and the University of California, Santa Barbara.

8 Validating the center’s leading-edge efforts, the California Institute for Regenerative Medicine (CIRM) awarded $27 million to fund construction of the Eli and Edythe Broad CIRM Center for Regenerative Medicine and Stem Cell Research at USC.

The progress we have already made is astounding, but our journey is far from over. While we are grateful for the generous financial support we’ve received, additional funding is needed.

Please join us on this transformative journey toward a future of new medicine.

Sincerely,

Carmen A. Puliafito, M.D., M.B.A.

Dean

Keck School of Medicine of USC

While a challenging journey remains, in the span of just two years the University of Southern California’s Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research and the Eli and Edythe Broad CIRM Center for Regenerative Medicine and Stem Cell Research at USC have made seminal strides in this rapidly emerging, quite possibly transformative field: