__MAIN_TEXT__

Page 1

Targets without Borders

MELANOMA LUNG CANCER

BRAIN CANCER

LEUKEMIA PANCREATIC CANCER

PROSTATE CANCER

BREAST CANCER

SANFORD BURNHAM PREBYS NCI-DESIGNATED CANCER CENTER

COLON CANCER


MISSION

VISION

Sanford Burnham Prebys Medical Discovery Institute conducts world-class collaborative research dedicated to finding cures for human disease, improving quality of life, and educating and training the next generation of scientists, thus creating a legacy for its employees, partners, donors and community.

The vision of our Cancer Center is to make paradigm-shifting discoveries that will underlie novel therapeutic modalities by creating, translating and disseminating exceptional basic cancer science.

We will attain this by: Conducting state-of-the-art, multidisciplinary basic research into the causes, prevention and treatment of cancer

Advancing our discoveries into early pre-clinical development for the benefit of cancer patients everywhere

117

cancer-related publications/year

39 faculty

$25M direct funding from all sources

15

Educating and training the next generation of cancer scientists

400

scientists working in collaborative, interactive programs

adjunct faculty

10

shared scientific core facilities

77

cancer projects

1

TARGETS WITHOUT BORDERS

Sanford Burnham Prebys is a U.S.-based nonprofit public benefit corporation, with operations in San Diego, Calif., (La Jolla).


TARGETING CANCER Image showing colorectal cancer cells stained for cytoskeleton (red), nuclei (blue) and the anti-cancer target ALDOA (green). Courtesy of Fabiana Izidro A. L. Layng, M.D., postdoctoral associate in the Powis lab


LETTER FROM THE DIRECTOR

Since our Institute opened in 1976, we have been on a mission to conquer cancer. Our world-class Cancer Center is fulfilling that mission, armed with new revelations about the root causes of cancer, state-of-the-art drug discovery capabilities and leading scientists who are relentless in Sanford Burnham Prebys’ quest, “From Research, the Power to Cure.” The National Cancer Institute (NCI) recognized our boundless potential to make meaningful scientific discoveries in 1981, when our co-founders, Dr. William and Lillian Fishman, were awarded a Cancer Center Support Grant. Today, we are one of seven NCI-designated basic research cancer centers in the nation, and a global leader in translating our discoveries to benefit human health. We are also one of four Comprehensive Centers for the NCI Chemical Biology Consortium (CBC). Membership in the CBC places Sanford Burnham Prebys in a highly collaborative partnership with the NCI and a network of academic and industry partners. Sanford Burnham Prebys has been home to some of the most significant biological studies in cancer. Our strength in basic biology research often identifies new cancer targets that can form the basis for small molecules or biological agents that have the potential for becoming new cancer therapies. Our strength in chemical biology, structural biology and pharmacology allows the development of such new therapies.

San Diego has the greatest cluster of biotech companies in the world, and the entrepreneurial ethos that this brings is part of our culture. As a result, a number of our faculty have set up biotech companies to help translate their discoveries into treatments for cancer patients. These strengths, along with our robust partnerships with pharmaceutical companies and healthcare systems, create the necessary infrastructure to advance novel disease interventions to clinical settings. In this publication, we introduce you to “Targets without Borders,” the foundation of our Cancer Center. We understand that cancers that arise from different organs can be driven by the same underlying biology. By studying cancer-causing genes and signals, we develop new approaches to bringing targeted, personalized treatment to more people living with cancer. Having spent my career in the field of oncology research, I know only too well that cancer is a very personal experience. Ultimately, everyone’s life will be touched by cancer. Maybe it's a friend. Maybe it’s a family member. Maybe it’s you. My colleagues and I are deeply committed to finding new ways to restore health and hope—for all of us.

“There have been so many advances in genomics, immunology, genetic engineering and information science— now is the time to use all these advances to speed the progress against cancer.”

GARTH POWIS, D.Phil. Center Director

SANFORD BURNHAM PREBYS NCI-DESIGNATED CANCER CENTER

2


TAKING AIM AT CANCER THE INSTITUTE’S NCI-DESIGNATED CANCER CENTER IS AT THE LEADING EDGE OF MOVING TODAY’S INNOVATIVE DISCOVERIES TOWARD THE CANCER SOLUTIONS OF TOMORROW

1

2

STEP

STEP

SOMETHING GOES WRONG IN A CELL, SENDING IT SPINNING OUT OF CONTROL

CANCER OVERRUNS CELL PROGRAMS, ALLOWING TUMORS TO TAKE ROOT

Investigators in the Tumor Initiation and Maintenance Program study the type of cells that give rise to tumors and the signals that allow these cells to expand uncontrollably. Their research not only deepens our understanding of cancer, but also points the way toward novel approaches to therapy.

The Cancer Metabolism and Signaling Networks Program explores the pathways and signals that tumors use to reprogram their metabolism to escape normal cell death. Understanding these pathways helps identify therapeutic targets and is critical for the design of tumor-specific, less toxic therapies.

3

TARGETS WITHOUT BORDERS


Cancer encompasses more than 200 disease types, and it can afflict more than 60 different organs in the body. But even with such multiplicity, we know that cancers share certain finite strategies for development, maintenance, survival, expansion and migration to other organs.

3

STEP

TARGETS WITHOUT BORDERS “Targets without Borders” is a conceptual foundation for much of the work in our NCI-designated Cancer Center. We now know that the targets for many of the cancer drugs that we and others are developing are found in multiple tumor types. We are looking at different cancers not by where they start, but at their blueprint and the way they metastasize. We have organized our research programs based on the hallmarks of cancer. For example, all cells must acquire genetic mutations to become cancerous. Once formed, tumors revamp their metabolism to acquire the necessary nutrients from a frequently nutrient-poor environment to survive and proliferate. And increasingly, we are learning how tumors remodel their environment to promote their growth while hijacking the immune system for their benefit. By grouping our cancer programs to match the steps that all cancers take, we create new opportunities for our discoveries to apply to different cancer types— independent of the tissue of origin. This approach maximizes our dedicated cancer research resources, but it still enables disease-specific research to generate advances in those areas.

200+ TUMORS CREATE A NICHE ENVIRONMENT TO SPREAD. THE IMMUNE SYSTEM CAN BE GUIDED TO FIGHT CANCER The Tumor Microenvironment and Cancer Immunology Program aims to understand how cells interact with each other and their environment to promote tumor growth. Researchers also study how the immune system is altered to promote tumor growth, and how we can harness the immune system to fight back and kill cancer cells.

different types of cancer

600,000 Americans died of cancer in 2018

1,700,000 new cases of cancer in the U.S. 2018

SANFORD BURNHAM PREBYS NCI-DESIGNATED CANCER CENTER

4


“Improved treatment of cancer will likely come from a better understanding of the genes and signals that control tumor development.”

RESEARCHER PROFILES

ROBERT WECHSLER-REYA, Ph.D. Professor and Director of the Tumor Initiation and Maintenance Program

MEDULLOBLASTOMA

2,900

children under the age of 20 are diagnosed with brain tumors each year in the U.S.

5

TARGETS WITHOUT BORDERS

Medulloblastoma is the most common malignant brain tumor in children. Despite aggressive therapy—including surgery, radiation and chemotherapy—many patients still die of the disease, and survivors may suffer lifelong cognitive deficits. Thus, more effective and less toxic therapies are needed. The Wechsler-Reya lab is exploring new treatment avenues using animal models to identify the cells from which medulloblastoma arises, the mutations that transform these cells into tumors and the signals that allow these cells to continue to grow and to evade therapy.

Dr. Wechsler-Reya holds an additional appointment as program director for the Joseph Clayes III Research Center for Neuro-Oncology and Genomics at Rady Children’s Institute for Genomic Medicine. In this capacity, he directs a team of physicians, biomedical scientists and computational biologists who use DNA, RNA and epigenetic profiles of patients’ tumors to define optimal therapeutic strategies for each individual. In conjunction with our Prebys Center, Dr. Wechsler-Reya and his collaborators are also carrying out high-throughput drug screens to identify new therapies that can be tested in the clinic to improve outcomes for children with brain tumors.


JORGE MOSCAT, Ph.D.

MARIA DIAZ-MECO, Ph.D.

Professor and Director of the Cancer Metabolism and Signaling Networks Program

Professor in the Cancer Metabolism and Signaling Networks Program

INTESTINAL AND LIVER CANCERS

PROSTATE CANCER

Inflammation is a risk factor and causative agent in cancer but especially in liver and intestinal tumors. Liver cancer is the consequence of a chronic process that in most cases is initiated by obesity and progresses through hepatitis and cirrhosis. Therefore, hepatocellular carcinomas are an example of crosstalk between metabolism and inflammation that results in cancer.

Prostate cancer initiation is induced by genetic changes and is irreversible. However, tumor promotion and progression are long-lasting processes that are susceptible to modulation and can even be reversed, thereby providing a rationale for therapeutic intervention. Central to the control of tumor progression is the concerted metabolic reprogramming across cancer and normal cellular compartments of the tumor microenvironment.

The laboratory of Dr. Moscat investigates how these metabolic and inflammatory signals can be controlled to prevent and treat liver carcinogenesis. Similarly, inflammatory bowel diseases are a risk factor for intestinal tumorigenesis. Dr. Moscat’s studies have unveiled two tumor suppressors, protein kinase C lambda/iota and protein kinase C zeta, which act in concert through unique pathways to regulate intestinal cell metabolism and immunity to prevent tumorigenesis. The loss of these genes results in the most aggressive form of colorectal cancer. Dr. Moscat’s lab aims to identify new targets in these pathways that can be susceptible to therapeutic intervention.

Dr. Diaz-Meco’s laboratory studies how prostate cancer cells communicate with their stroma to survive and grow under conditions of nutrient deficiency, a situation often found in very aggressive and therapy-resistant tumors. Her findings establish a new paradigm whereby a protein termed p62 enters into the nucleus of stromal cells to interact with critical transcription factors that are master regulators of cancer metabolism. These findings identify p62 as a new therapeutic target in the most aggressive forms of prostate cancer.

SANFORD BURNHAM PREBYS NCI-DESIGNATED CANCER CENTER

6


“I’m optimistic that we are still at the beginning of harnessing the immune system to battle cancer.” LINDA BRADLEY, Ph.D. Professor and Director of the Tumor Microenvironment and Cancer Immunology Program

IMMUNOTHERAPY Research in Dr. Bradley’s lab focuses on understanding the regulation of T cells and applying the findings to the development of novel immunotherapies for patients with cancer. Recently, Dr. Bradley’s work led to the identification of a protein called PSGL-1 that’s required to increase levels of immune checkpoints on T cells. Cancer cells can trick the immune system to help tumors survive and grow.

7

TARGETS WITHOUT BORDERS

Immune checkpoints are the molecules that control the strength of an immune response. Tumors have unique ways of controlling checkpoints to turn the immune system down so that they can grow and thrive.

PSGL-1 limits the immune system’s ability to battle cancer by increasing the levels of checkpoint molecules. Dr. Bradley’s lab found that when PSGL-1 is missing in mouse models of melanoma, the immune brakes are off, and the system is able to respond to cancer. In addition to seeking PSGL-1 inhibitors that can be tested in the clinic, Dr. Bradley is developing unique mouse models that contain fragments of patient tumors. The project will help physicians at UC San Diego Moores Cancer Center select which drugs, or combinations of drugs, might work best for that particular patient.


ZE’EV RONAI, Ph.D. Professor in the Tumor Initiation and Maintenance Program

MELANOMA Malignant melanoma is a highly aggressive, life-threatening cancer due to its propensity to metastasize and resist therapies. The development of immunotherapies combined with drugs that target major drivers of melanoma, such as BRAF and MEK, has revolutionized melanoma treatment, often extending patient survival by years. Yet, not all patients respond to these therapies, and many relapse as their tumors adapt or resist them. Dr. Ronai’s lab is identifying novel pathways that drive melanoma. Recently his work revealed the importance of the enzyme PRMT5, which is downregulated in nearly 40 percent of melanoma tumors.

Patients with these tumors may be more responsive to PRMT5 inhibitors in future clinical trials. The small molecule SBI-756 identified in Dr. Ronai’s lab targets an important cellular machine—protein translation control—and is being evaluated in preclinical studies of melanoma and other aggressive tumors. Finally, the sensor ATF4, also studied in Dr. Ronai’s lab, plays a critical role in controlling metabolic processes that are rewired in tumors such as melanoma to support their growth and survival. Identifying promising disease targets may lead to the development of new drugs to better fight the battle against melanoma.

1 One American dies from melanoma every hour.

SANFORD BURNHAM PREBYS NCI-DESIGNATED CANCER CENTER

8


“We believe we can greatly improve the efficacy of cancer drugs in solid tumors.�

ERKKI RUOSLAHTI, M.D., Ph.D. Distinguished Professor in the Tumor Microenvironment and Cancer Immunology Program

SOLID TUMORS

An electron micrograph illustrating the CEND-1 induced transport system in process. Reprint permission from the American Chemical Society.

9

TARGETS WITHOUT BORDERS

Solid tumors, such as pancreatic cancer, are difficult to treat. The tumor cells are often surrounded by thick fibrotic tissue, making it hard for treatments to reach them. As a result, many solid tumors are also some of the deadliest, including brain, ovarian and pancreatic cancer. Pancreatic cancer is one of the few cancers for which survival has not improved substantially for more than 40 years.

The compound harnesses a transport pathway that is thought to ferry nutrients to tissues that are nutrient deficient. Cancer cells hijack processes they can use to fuel tumor growth, and the CENDR pathway is one such route. CEND-1 activates the CENDR pathway only in tumors and not elsewhere in the body, allowing cancer drugs to sneak into tumors when co-administered with the compound.

Dr. Erkki Ruoslahti and his colleagues have developed a compound called CEND-1 (scientifically known as iRGD) that overcomes this barrier, allowing cancer treatments to penetrate farther into solid tumors.

CEND-1 has been licensed to DrugCendR Inc., a company founded by Dr. Ruoslahti. CEND-1 recently advanced into a Phase 1 trial for metastatic pancreatic cancer.


COSIMO COMMISSO, Ph.D. Assistant Professor in the Tumor Initiation and Maintenance Program

PANCREATIC CANCER Dr. Commisso’s lab studies the biology of pancreatic cancer, which is an extremely aggressive disease and is in urgent need of new and innovative therapies. Most pancreatic tumors have a mutation in a gene called Ras. Ras is an oncogene that becomes activated when mutated, changing the function of the protein and creating the malignant properties that are needed for cancer to grow and survive. Tumors harboring an oncogenic Ras protein have increased nutrient uptake through micropinocytosis, a type of “cell drinking” that provides much-needed amino acids to fuel cancer metabolism and growth.

These insights were initially demonstrated by Dr. Commisso’s research. His work now focuses on advancing our understanding of macropinocytosis and strategies to target this pathway with anti-cancer drugs as a means to “starve” tumors. He is also focusing on ways to exploit the pathway to encourage the delivery and uptake of therapeutic agents, such as nanoparticles. Dr. Commisso was recently named a NextGen Star by the American Association for Cancer Research.

“The 5-year survival rate for pancreatic cancer is less than 10%, which is why new therapies are desperately needed for these patients.”

SANFORD BURNHAM PREBYS NCI-DESIGNATED CANCER CENTER

10


AML

LUNG

PANCREATIC

BREAST

BRAIN

ONCOLOGY DISEASE TEAMS ONCOLOGY DISEASE TEAMS PROVIDE RESEARCHERS A LINE OF SIGHT TO THE CLINIC AND THE CANCER PATIENTS WE ARE TRYING TO HELP.

Our Cancer Center is unique among basic science cancer centers. We have formed Oncology Disease Teams for challenging cancers: AML, brain, breast, lung and pancreatic cancer. We work with clinicians from UC San Diego Moores Cancer Center, Rady Children’s Hospital and the new Scripps Health/ MD Anderson Cancer Center to help transition research innovations into viable disease-specific therapeutics.

11

TARGETS WITHOUT BORDERS


TEAM BREAST CANCER

TEAM ACUTE MYELOID LEUKEMIA

Triple negative breast cancer (TNBC) means the cancer cells don’t have the three most common receptors known to fuel breast cancer: estrogen, progesterone and HER2. These tumors account for 15 to 20 percent of cases and are more aggressive than other forms—many are fatal within the first five years of diagnosis. The majority of breast cancers are estrogen receptor-positive (ERpositive). Hormone therapies (anti-estrogen drugs) are available, but this treatment doesn’t work for 40 percent of women with ER-positive breast cancer.

BROOKE EMERLING, Ph.D.

SVASTI HARICHARAN, Ph.D.

Assistant Professor in the Cancer Metabolism and Signaling Networks Program

Assistant Professor in the Tumor Microenvironment and Cancer Immunology Program

Dr. Brooke Emerling’s lab studies the adaptive mechanisms that tumors use to successfully compete for the ever-diminishing supply of nutrients in their surroundings. One mechanism, called autophagy, provides nutrients by recycling cellular compartments to generate fuel. Dr. Emerling’s recent work identified enzymes in the PI5P4K family as critical for the autophagy process. Deficiencies in these enzymes dramatically reduce tumor formation and increase tumor-free survival in mice, suggesting that inhibitors of PI5P4K may be an effective therapy for certain cancers, including TNBC.

Dr. Haricharan’s research has revealed that about one-third of women with ER-positive breast cancer who are treatment resistant have a mutation in DNA damage-repair genes. Her lab now focuses on developing a test for the mutation to predict who will respond to hormone therapy. Knowing up front if an individual will benefit from a therapy allows doctors to skip treatments that don’t work and move immediately to medicines that may be effective. Pairing a new test with an effective therapeutic option would be an important advance for ER-positive breast cancer patients.

Acute myeloid leukemia (AML) is a type of blood cancer that starts with the uncontrolled proliferation of myeloid precursor cells (immature blood cells) in the bone marrow. AML can rapidly spread to the blood and other parts of the body and is life threatening. For most patients, toxic chemotherapy is the only treatment option, and the five-year overall survival rate is less than 30 percent. AML makes up more than 30 percent of adult leukemia cases.

ANI DESHPANDE, Ph.D.

PETER ADAMS, Ph.D.

Assistant Professor in the Tumor Initiation and Maintenance Program

Professor in the Tumor Initiation and Maintenance Program

The Deshpande lab is investigating how epigenetic modifications regulate chromatin—a key step in the transcriptional activation of genes. In AML, the transcriptional processes of cancer cells have gone awry, causing the accumulation of immature, non-functioning malignant cells. Epigenetic alterations are pharmacologically reversible and represent optimal targets for therapy. His lab is working toward drug screens to develop therapeutics that target the dysregulated epigenetic mechanisms in AML.

Dr. Adams’ lab studies the impact of histones, chromatin and epigenetics on cell senescence. Histones—the proteins that condense and package DNA into chromatin—create epigenetic patterns of our genome that influence gene expression and change as we age. By dissecting the mechanisms distinguishing healthy and aging epigenetic profiles, Dr. Adams’ research may lead to therapeutic interventions to reverse detrimental epigenetic modifications linked to age-associated diseases, including cancer.

SANFORD BURNHAM PREBYS NCI-DESIGNATED CANCER CENTER

12


NAVIGATING CANCER DRUG DISCOVERY Nicholas Cosford, Ph.D., deputy director of the Cancer Center, initiates drug discovery for his most innovative and exciting new targets in the Prebys Center.

Dr. Cosford initially joined Sanford Burnham Prebys as the project manager for the Conrad Prebys Center for Chemical Genomics (Prebys Center). Working with Professor José Luis Millán at that time, he directed the screening and early discovery efforts that led to a drug, currently in Phase I clinical trials for kidney disease, which acts by inhibiting a class of proteins called phosphatases. Dr. Cosford has now teamed with Dr. Lutz Tautz to work on a different class of phosphatase enzymes that are involved in several aggressive forms of cancer. It has been known for some time that one of these phosphatases, called Shp2, is mutated or activated in cancers found in brain, breast, lung, prostate and leukemia. However, until very recently it was thought that this class of enzymes was “undruggable” because it couldn't be affected by drugs. Now the team is working with the Prebys Center to screen thousands of compounds to find inhibitors of Shp2 that can be optimized into new medicines to fight these deadly cancers. They have developed a novel screening platform to find so-called allosteric inhibitors, which are known to be more selective for their target, and therefore are expected to have a lower risk of severe side effects when given as a drug. This project has been accepted into the National Cancer Institute Experimental Therapeutics Program (NExT), which provides research funding for the development of novel cancer therapies from early discovery all the way to clinical development.

13

TARGETS WITHOUT BORDERS


Nicholas Cosford, Ph.D., (left); and Lutz Tautz, Ph.D.

Michael Jackson, Ph.D., senior vice president, Drug Discovery and Development

PARTNERING WITH THE PREBYS CENTER FOR SUCCESS THE PREBYS CENTER IS ONE OF THE MOST ADVANCED DRUG DISCOVERY FACILITIES IN THE NONPROFIT WORLD

The Prebys Center uses robotic technology to systematically search through hundreds of thousands of chemical compounds to find the few that are potential starting points for new medicines. We have achieved national recognition as experts in assay development, high-throughput screening and lead optimization, and have been selected as one of four comprehensive probe/discovery centers of the NIH Molecular Libraries Probe Production Centers Network (MLPCN) and one of seven comprehensive centers in the NCI’s Chemical Biology Consortium.

“By working with partners and combining expertise, our Prebys Center has been shortening the distance between basic cancer research findings and therapeutics discovery.”

“Our vision is to be the world’s leading academic drug discovery organization, an epicenter for innovative approaches to accelerating the discovery of new drugs to save lives and treat disease,” says Michael Jackson, Ph.D., senior vice president of Drug Discovery and Development.

SANFORD BURNHAM PREBYS NCI-DESIGNATED CANCER CENTER

14


CORE FACILITIES THERE ARE CURRENTLY 10 CORE FACILITIES WITH ADVANCED TECHNOLOGY STAFFED BY TECHNICAL EXPERTS IN EACH FIELD

The shared resources of the NCI-designated Cancer Center are specialized service facilities that support the cancer research efforts of our members, as well as other nonprofit and for-profit investigators in cancer research.

BIOINFORMATICS

CANCER METABOLISM

PROTEOMICS

Scientific research produces vast amounts of data. Creating knowledge from data requires the use of sophisticated bioinformatics tools. This facility provides the tools and expertise to understand the biological and medical significance of research discoveries, through the analysis, integration, mining and contextualizing of data.

The cancer metabolism facility provides analytical services to measure metabolic flux, cellular metabolites and cellular respiration measurements. The findings improve our understanding of the metabolic alterations associated with cancers and how they can be therapeutically targeted.

Researchers use the proteomics facility to understand which proteins are expressed or modified in normal cells compared to cancer cells. Technologies range from mass spec and gel-based simple protein identification to proteome-wide, post-translational modification analysis.

CELL IMAGING AND HISTOLOGY

STRUCTURAL BIOLOGY

FUNCTIONAL GENOMICS

In the cell imaging facility, we provide access to many types of microscopes, including bright field, fluorescence, confocal and multiphoton confocal microscopes. Histopathology services include tissue section analysis, staining, IHC, laser capture microscopy, high-resolution slide scanning and assistance with tissue procurement and pathology analysis.

The structural biology core offers central tools used to develop a complete picture of proteins at an atomic level and gives scientists insights as to protein functions, flaws resulting from genetic mutations and drug interactions. Technologies include nuclear magnetic resonance, crystallography and protein analysis.

Functional genomics focuses on the dynamic aspects of genes such as gene transcription, translation and protein-protein interactions—as well as the role of noncoding RNA in cell function. This core facility provides assay development, RNA and DNA libraries, and high-throughput screening services.

ANIMAL RESOURCES

FLOW CYTOMETRY

CHEMICAL LIBRARY SCREENING

Our animal resources include an AAALACaccredited animal facility, with a variety of animal analysis technologies including animal imaging, analysis of tumor formation and treatment results.

Flow cytometry allows scientists to count and sort cells based on biomarker expression on cell surfaces. The flow cytometry facility provides both analytical and high-speed cell-sorting services.

This core utilizes the extensive resources in the Prebys Center to support chemical biology, drug discovery and drug development.

15

TARGETS WITHOUT BORDERS


SINGLE-CELL SEQUENCING

“We have been uncovering new and unexpected insights into the biology of cancer by isolating and analyzing individual cells in tumors.” BRIAN JAMES, Ph.D. Facility Director

GENOMICS Genomic studies allow scientists to understand the role that specific genes play in cancer. Our facility provides next-gen sequencing including experimental design, library prep, single-cell sequencing and data analysis, as well as full-service microarray and Q-PCR analysis.

Studying cancer at the single-cell level Rapid progress in the field of sequencing genetic material has provided valuable insights into the complex world of cancer.

“What we do is tease out the individual cells in tumors—the normal cells, the cancer cells and even the immune cells recruited to fight cancer—and examine the genes that are activated in each individual cell type,” says Brian James, Ph.D., co-organizer of the C3 Single Cell Working Group and facility director of Sanford Burnham Prebys' genomics core. “This gives us a lot of information about which genes are driving the cancer, how drugs are working and if a cancer is becoming resistant to therapy.”

SANFORD BURNHAM PREBYS NCI-DESIGNATED CANCER CENTER

16


Robert Wechsler-Reya, Ph.D., director and professor of the Tumor Initiation and Maintenance Program (left); and John Crawford, M.D.,

POWER OF PARTNERSHIPS NO SINGLE INVESTIGATOR HAS THE KNOWLEDGE OR RESOURCES NEEDED TO BATTLE A DISEASE AS COMPLEX AS CANCER

director of Pediatric Neuro-Oncology at Rady Children’s Hospital.

Partners include: • Boston Children’s Hospital • Cedars-Sinai Medical Center • Dana-Farber Cancer Institute

“We join forces with clinical researchers from the world’s top cancer institutions to move our discoveries from ‘bench to bedside.’ ”

• Massachusetts General Hospital • Mayo Clinic • MD Anderson Cancer Center • Memorial Sloan Kettering Cancer Center

ROBERT WECHSLER-REYA, Ph.D.

• Rady Children’s Hospital • St. Jude Children’s Research Hospital

Our expertise in investigative laboratory discoveries, combined with the clinical observations and practices of our partners, creates opportunities to make meaningful advances in the prevention, diagnosis and treatment of cancer.

17

TARGETS WITHOUT BORDERS

• UC San Diego Moores Cancer Center


CONTRIBUTIONS TO CANCER RESEARCH

PROSTATE CANCER

CHEMOTHERAPY SIDE EFFECTS

LYMPHOMA

Invented the technology used in the PSA test—the world’s only blood test for the detection of prostate cancer

Generated the technology that enabled the development of the drug Epogen®—approved by the FDA to treat anemia caused by chemotherapy

Performed research that helped identify Targretin®— an FDA-approved drug for the treatment of cutaneous T-cell lymphoma

PANCREATIC CANCER

BREAST CANCER

LYMPHOID CANCER

Created the technology for CEND-1, a compound that helps anti-cancer drugs penetrate tumors—in clinical trials for pancreatic cancer

Research guided clinical trial design for CB-839—a glutaminase inhibitor in clinical trials for breast cancer

Substantiated the anti-tumor properties of navitoclax—in clinical trials for lymphoid cancers

Clinical trials are an essential path to advance innovative research and light the way toward better therapies. We have a solid history of breakthrough research that directly impacts the future of life-saving treatments.

SOLID TUMORS

LYMPHOMA

Validated the biological action of birinapant—in clinical trials for solid tumors

Produced foundational research for NGR-hTNF—in clinical trials for lymphoma

BRAIN CANCER

HEMATOLOGICAL CANCER

COLORECTAL CANCER

Pioneered research leading to a clinical trial testing the HDACPI3K inhibitor CUDC-907 in children with brain cancer

Established foundational research leading to Venclexta®— FDA approved for the treatment of hematological cancers

Discovered TX803—a first-in-class therapeutic in clinical trials for colorectal cancer

SANFORD BURNHAM PREBYS NCI-DESIGNATED CANCER CENTER

18


From left to right: Corey Bretz, Ph.D., Szu-Wei Lee, Ph.D., Jon Gist, Ph.D., Nicole Bakas, Ph.D., Scotty Cadet, Jennifer Hope Gracias, Ph.D.

“Our aim is to develop the next generation of world-class cancer researchers.” GARTH POWIS, D.Phil.

CAREERS IN CANCER RESEARCH SANFORD BURNHAM PREBYS HELPS EARLY-CAREER SCIENTISTS NAVIGATE THE PATH TO SUCCESS IN SCIENCE

The National Institutes of Health (NIH) recognizes the need to invest in training scientists to meet the health-related needs of the nation. Institutional Research Training Grants (T32) are one of the ways the NIH is supporting the goal.

experiences in advanced technologies supported by our state-of-the-art core facilities.”

Sanford Burnham Prebys is the proud recipient of T32 grants—awards that allow faculty to select pre-doctoral and postdoctoral researchers for training in the technologies, skills and values needed to achieve a successful career in biomedical research.

“I am honored to have been selected to participate in the T32 training program Cancer Targets and New Drug Discovery to advance my career in translational research,” says Nicole Bakas, Ph.D. “A unique feature of the program is a two-month biotech internship that gives me the opportunity to engage in scientific entrepreneurship and explore careers in biopharma as well as academia.”

“Our trainees are selected based on scientific and academic accomplishments, as well as suitability for research projects and commitment to a scientific career,” says Garth Powis, D.Phil., director of our NCI-designated Cancer Center. “The selected individuals are guided by mentoring committees and provided well-rounded training

“The Frontiers in Fundamental and Translational Immunology program is a tremendous opportunity for me to work with leaders in the field of patient-focused immunology research,” says Jennifer Hope, Ph.D. “I’m fortunate to be working with experts at the interface between basic research and early-stage drug discovery.”

19

TARGETS WITHOUT BORDERS


GRADUATE SCHOOL OF BIOMEDICAL SCIENCES The Sanford Burnham Prebys Graduate School provides students with a solid foundation in biology, chemistry, bioinformatics and engineering to support careers that advance medicine and health care.

MEET A GRADUATE STUDENT

Marisa Sanchez is a graduate student in the lab of Dieter Wolf, M.D.

MARISA SANCHEZ IS ON A MISSION TO ADVANCE MEDICINE

What research highlights have you achieved?

Marisa with her sister Alessandra

What inspired you to pursue a graduate degree in biomedical science? Ever since I can remember, I was enthralled by science. I was always drawn to the complexity of the human body. I also have a strong desire to give back to society, and biomedical research is the perfect combination of exploring the fundamentals of human life and disease while making a difference. The idea of doing something new every day—something that no one else has ever done—creates a sense of adventure.

Why cancer? First, cancer kills. It’s second only to heart disease in the cause of deaths in the U.S. Next, cancer kills too early. I know this all too well. I lost my younger sister Alessandra when she was only 19 to Hodgkin’s lymphoma. I’m driven to research to help solve the mysteries of cancer and prevent others from suffering such a devastating loss. Progress is possible! The survival rates for many types of cancer are improving. New drugs are being developed, new technologies are available and we are finding more paths that will lead to curing this very complicated disease.

I have identified novel insights into how different factors involving protein synthesis communicate with each other under certain cellular stress conditions in order to protect the cell. This is important because cancer cells are constantly exposed to toxic levels of stress, but still survive. My research can help us understand how cancer cells can manipulate these stress-response pathways to avoid cell death and continue to grow uncontrollably. What are your career plans? After graduation, I plan to join a company in the pharmaceutical or biotech industry as a scientist or liaison for the scientific and medical community. I would love to work with products or technologies that focus on the advancement of clinical treatments for cancer and other diseases. Ultimately, my goal is to use my passion to make a significant contribution in my field that will help people.

SANFORD BURNHAM PREBYS NCI-DESIGNATED CANCER CENTER

20


SANFORD BURNHAM PREBYS CANCER CENTER

COMMUNITY ADVISORY BOARD The Community Advisory Board (CAB) is a group of nonscientist volunteers who advocate for the Cancer Center faculty. They provide an essential link with local, national and global communities. The group is comprised of cancer survivors, family members, educators and business leaders working toward the goal of eliminating the burden of cancer.

21

TARGETS WITHOUT BORDERS

Helen Eckmann, Ed.D., (left) and Ruth Claire Black, Ed.D., J.D.


Garth Powis, D.Phil., and members of the CAB

“The CAB acts as a bridge between Sanford Burnham Prebys and the community, helping researchers understand the kinds of questions and concerns the public may have,” says Garth Powis, D.Phil., director of the Cancer Center. “The members also play an important role in helping the community understand the science that’s being conducted, and how it may improve the prevention, diagnosis and treatment of cancer.”

“I got involved with the CAB because I’m a survivor,” says Helen Eckmann, Ed.D., who has gone through treatment for breast cancer three times. “Instead of sitting passively and waiting for others to take action, I wanted to do something. I wanted to put all that I have into helping find ways to bring relief and remission.”

Ruth Claire Black, Ed.D., J.D., also a breast cancer survivor, echoed the drive to make a difference: “I feel that I have a responsibility to support research and young scientists. I don’t think we will find cures without advocacy.”

Twice a year the CAB sponsors Cancer Center Open House events that attract a wide array of visitors—from high school students to Board Trustees. For some people, it’s the first time they visit our Institute to learn about our pioneering research. For others, it’s an opportunity to connect with old friends and visit a research organization they support with great passion.

SANFORD BURNHAM PREBYS NCI-DESIGNATED CANCER CENTER

22


“Cancer is a disease that impacts all of us,” says James Short, Sanford Burnham Prebys’ team captain. “It can make you feel helpless, but Padres Pedal the Cause supports people working together to have an impact on cancer, in big and lasting ways.”

TEAM SPIRIT AT PADRES PEDAL THE CAUSE THE ANNUAL EVENT IS NOW ONE OF SAN DIEGO’S PREMIER CANCER RESEARCH FUNDRAISERS

“My award from Padres Pedal the Cause provided seed funding for a collaboration with Jack Bui, M.D., Ph.D., at the UC San Diego Moores Cancer Center. We are working on ways to turn ‘cold’ tumors that immune cells ignore into 'hot' tumors that attract immune cells. This could improve the effectiveness of immunotherapies for treating cancer.”

Padres Pedal the Cause (PPTC) is a one-day event that invites participants to cycle, spin, run or walk to raise funds for local cancer research. Since the inaugural ride in 2013, more than $10 million has been raised, with 100 percent of the proceeds funding research collaborations between Sanford Burnham Prebys, Moores Cancer Center at UC San Diego Health, Salk Institute for Biological Research and Rady Children’s Hospital. In November 2018, there were more than 2,500 participants, including our team of 60 inspired scientists, staff and supporters. Past PPTC grants have accelerated our research collaborations on breast, skin, pancreatic, colorectal and brain cancer.

PETER ADAMS, Ph.D. Professor / Sanford Burnham Prebys Cancer Center

SANFORD BURNHAM PREBYS NCI-DESIGNATED CANCER CENTER LEADERSHIP

GARTH POWIS, D. Phil.

ROBERT WECHSLER-REYA, Ph.D.

LINDA BRADLEY, Ph.D.

GUY SALVESEN, Ph.D.

Center Director

Director, Tumor Initiation and Maintenance Program

Director, Tumor Microenvironment and Cancer Immunology Program

Associate Director, Education and Mentoring

NICHOLAS COSFORD Ph.D.

JORGE MOSCAT, Ph.D.

CRAIG HAUSER, Ph.D.

ADRIENNE CROWN, J.D.

Deputy Director

Director, Cancer Metabolism and Signaling Networks Program

Associate Director, Shared Resources

Associate Director, Cancer Center Administration

23

TARGETS WITHOUT BORDERS


SANFORD BURNHAM PREBYS NCI-DESIGNATED CANCER CENTER FACULTY PROGRAM 1

PROGRAM 2

PROGRAM 3

TUMOR INITIATION AND MAINTENANCE (TIM)

CANCER METABOLISM AND SIGNALING NETWORKS (CMSN)

TUMOR MICROENVIRONMENT AND CANCER IMMUNOLOGY (TMCI)

ROBERT WECHSLER-REYA, Ph.D.

JORGE MOSCAT, Ph.D.

LINDA BRADLEY, Ph.D.

Program Director

Program Director

Program Director

Peter Adams, Ph.D. Anindya Bagchi, Ph.D. Rolf Bodmer, Ph.D. Cosimo Commisso, Ph.D. Maximiliano D’Angelo, Ph.D. Aniruddha Deshpande, Ph.D. Elena Pasquale, Ph.D. Matthew Petroski, Ph.D. Pier Lorenzo Puri, M.D., Ph.D. Ze’ev Ronai, Ph.D. Alessandra Sacco, Ph.D. Evan Snyder, M.D., Ph.D. Charles Spruck, Ph.D. Alexey Terskikh, Ph.D. Jing Crystal Zhao, Ph.D.

Nicholas Cosford, Ph.D. Maria Diaz-Meco, Ph.D Brooke Emerling, Ph.D. Malene Hansen, Ph.D. Randal Kaufman, Ph.D. Francesca Marassi, Ph.D. Andrei Osterman, Ph.D. Stefan Riedl, Ph.D. Jeffrey Smith, Ph.D.

Sumit Chanda, Ph.D. Dorit Hanein, Ph.D. Svasti Haricharan, Ph.D. Robert Liddington, Ph.D. Scott Peterson, Ph.D. Garth Powis, D. Phil. Barbara Ranscht, Ph.D. Erkki Ruoslahti, M.D., Ph.D. Guy Salvesen, Ph.D. Niels Volkmann, Ph.D. Kristiina Vuori, M.D., Ph.D. Carl Ware, Ph.D.

ADJUNCTS

Robert Abraham, Ph.D. Adam Godzik, Ph.D. Michael Jackson, Ph.D. Maurizio Pellecchia, Ph.D. John Reed, M.D., Ph.D.

ADJUNCTS

Craig Hauser, Ph.D. Ranjan Perera, Ph.D. Manuel Perucho, Ph.D. Tariq Rana, Ph.D. Xiao-Kun Zhang, Ph.D.

ADJUNCTS

Sara Courtneidge, Ph.D. Masanobu Komatsu, Ph.D. Tomas Mustelin, M.D., Ph.D. Robert Rickert, Ph.D. Tambet Teesalu, Ph.D.

CANCER CENTER EXTERNAL ADVISORY BOARD

CHAIRED BY:

ADDITIONAL MEMBERS INCLUDE:

KENNETH TEW, Ph.D., D.Sc.

DAVID SCHEINBERG M.D., Ph.D.

WILLIAM S. DALTON, M.D., Ph.D.

ALEC C. KIMMELMAN, M.D., Ph.D.

KEVAN SHOKAT, Ph.D.

Professor and Chairman, John C. West Chair of Cancer Research, Medical University of South Carolina

Chair, Molecular Pharmacology Program, Sloan Kettering Institute Director, Center for Experimental Therapeutics, Memorial Sloan Kettering Cancer Center

Founder and Executive Chair, M2GEN

Professor and Chair, Department of Radiation Oncology, Perlmutter Cancer Center, NYU Langone Health

Professor and Chair, Department of Cellular and Molecular Pharmacology, UCSF Professor, Department of Chemistry, UC Berkeley

ROBERT B. DIASIO, M.D. Director, Mayo Clinic Cancer Center

M. CELESTE SIMON, Ph.D. Scientific Director, The Abramson Family Cancer Research Institute Professor, Department of Cell and Developmental Biology, University of Pennsylvania Perleman School of Medicine

LISA SIDERAS Associate Director, Cancer Center Administration, The Wistar Institute Cancer Center

SANFORD BURNHAM PREBYS NCI-DESIGNATED CANCER CENTER

24


CONTACT

Find more cancer news, information and events at sbpdiscovery.org

Profile for Sanford Burnham Prebys Medical Discovery Institute

Sanford Burnham Prebys Cancer Center  

NCI-designated Cancer Center

Sanford Burnham Prebys Cancer Center  

NCI-designated Cancer Center