PanCAN Summit Attendees
■Dr. Mariano Barbacid
Dr. Mariano Barbacid was born in Madrid, Spain, in 1949. From 1971 to 1974, he did his Ph.D. thesis at the Centro de Investigaciones Biológicas - CSIC getting his Ph.D. degree in Biochemistry at the Universidad Complutense de Madrid. From 1974-1978 Barbacid was a postdoctoral fellow in the National Cancer Institute in Bethesda, Maryland. In 1978 he formed his own group to work on the molecular biology of sarcoma viruses. At that time, he explored the possibility that human tumors may carry activated oncogenes similar to those found in transforming retroviruses. This work led to the identification and cloning of the first human oncogene in 1982 and its subsequent identification as a mutated allele of the H-ras proto-oncogene.

In 1984, Barbacid moved to the Basic Research Programme – NCI, FCRF, in Frederick Maryland as Head of the Developmental Oncology Section and in 1988, he joined the Bristol Myers-Squibb Pharmaceutical Research Institute in Princeton, New Jersey where he became Vice President, Oncology Drug Discovery in 1995. From 1995 until 1997, he implemented a target-based drug discovery programme that focused on farnesyl transferase and cell cycle inhibitors, some of which are currently in clinical trials. As part of his basic research efforts during his tenure at Bristol Myers-Squibb, it is worth mentioning the identification of the Trk family of tyrosine protein kinases as the neurotrophin receptors in 1991.
The relevance of his work has been recognised by several awards, among others, the Distinguished Young Scientist Award (Maryland Academy of Sciences, 1983), the “Rey Juan Carlos I” Award (Spain, 1984), the Rhodes Award of the American Association of Cancer Research (USA, 1986), the Steiner Prize (Switzerland, 1988), the Ipsen Prize (France, 1994) and most recently the Charles Rodolphe Brupbacher Prize that he will receive next March in Zurich along with Klaus Rajewsky. In addition, Barbacid has a Doctorate Honoris causa by the Universidad Internacional “Menéndez Pelayo” in Spain (1995) and has been an EMBO Member since 1996.
In 1998, Barbacid returned to Spain to create and subsequently direct the Centro Nacional de Investigaciones Oncológicas (CNIO). He combines his responsibilities as CNIO Director with his research activities as Head of the Experimental Oncology Group which concentrates on the study of the role of cell cycle regulators in vivo and on the design of new animal models for cancer by using gene-targeting technologies.
Barbacid has an outstanding list of publications, with 168 original papers in international scientific journals and 52 invited reviews and book chapters. He serves on numerous Scientific Advisory Committees and belongs to the Editorial Board of more than fifteen international scientific journals.

■Dr. Dafna Bar-Sagi
Dr. Sagi earned her undergraduate and master’s degree from Bar-Ilan University and her Ph.D. from SUNY at Stony Brook. After receiving her doctorate, she joined Cold Spring Harbor Laboratory on Long Island as a postdoctoral fellow; eventually serving as a Senior Staff Investigator there. Dr. Bar-Sagi then joined SUNY as an Associate Professor in the Department of Molecular Genetics and Microbiology; ultimately serving as Chairwoman of the Department.

A prolific researcher, Dr. Bar-Sagi has published more than 100 peer-reviewed research papers in leading journals on a wide range of topics centered on the molecular mechanisms underlying tumor and blood vessel formation, and survival of cells. Dr. Bar-Sagi has devoted considerable research to ras proteins, essential elements in complex pathways that control cellular growth. Ras proteins have captured the interest of cancer researchers for many years because abnormal forms of the proteins are present in many types of tumors.

Dr. Bar-Sagi has received many prestigious grants, including most recently a MERIT award (for Method to Extend Research in Time) from the National Institutes of Health. This highly competitive grant frees researchers who are widely recognized as leaders in their fields from the need to reapply for funding every three or four years. The award allows her to concentrate on ras proteins and their role in pancreatic cancer, which is her main research focus.

Dr. Bar-Sagi is an editor of Molecular and Cellular Biology and serves on the editorial boards of other journals and on the board of scientific counselors for the National Cancer Institute.

■Dr. Nabeel Bardeesy

Our laboratory studies the biological and molecular processes driving gastrointestinal malignancies, focusing primarily on pancreatic cancer. It is clear that clinical advances will require improved understanding of the biology of this malignancy. Key research questions include the need to identify the roles of specific gene mutations in the tumorigenic program and to determine how the cellular context in which the mutations occur influences the activity of these genetic lesions.

Genetic Determinants of Pancreatic Cancer: Pancreatic cancer appears to evolve through the multi-stage progression of a series of distinct precursor lesions. It is notable that the set of recurrent gene mutations associated with pancreatic cancer are first detected at specific pre-malignant stages, suggesting there may be an ordered program for tumor progression. These genetic alterations include the early stage activation of the KRAS oncogene, followed by the sequential loss of function of the INK4A/ARF, p53 and SMAD4 tumor suppressors at progressively later neoplastic stages. T he molecular circuitry engaged by these genetic alterations and the cell type that incurs such mutations are not clear. With this cancer genetics information as a guide, we are using biological systems to investigate the genetic determinants of the pancreatic cancer phenotype and to elucidate the circuitry that guides the processes of cancer initiation and progression.

We have developed a series of engineered mouse models harboring the recurrent genetic alterations in human pancreatic cancer. These models have established that activation of KRAS is sufficient to initiate the pre-malignant stages of this disease and that the INK4A/ARF tumor suppressor locus serves as a potent inhibitor of progression of these lesions. To detail the stage-specific roles of the full complement of the various pancreatic cancer mutations we have generated in vivo systems that enable the temporal control of activation and inactivation of these tumor suppressors and oncogenes. We expect that these studies will provide a direct mechanistic view of how the characteristic genetic lesions influence tumor biology.

The Cellular Origins of Pancreatic Cancer: Pancreatic cancer is thought to arise from premalignant lesions known as pancreatic intraepithelial neoplasms (PanINs). Early grade PanINs are detected in a significant proportion of autopsy specimens, making these lesions among the most common neoplasms in humans. Given this high prevalence and the propensity of these lesions to undergo malignant progression, the identification of the cell-of-origin of PanIN, and the definition of the biochemical and biological changes regulating the transformation of these target cells, may inform improvements in early detection and prevention of pancreatic cancer. The cell-of-origin question is of particular significance since recent evidence has shown that differences in cell type and cell context determine the biological and biochemical impact of an oncogenic mutation. We are employing transgenic mouse techniques to investigate the roles of specific pancreatic lineages in the initiation of this disease.

Therapeutic Targeting of the PI3K/AKT pathway: We maintain an active interest in translating basic science advances into clinically relevant applications. The phosphoinositide-3-kinase/AKT signaling pathway is central to cell growth and survival of many cancers and is inhibitors to numerous inhibitors of pathway components are under development by pharmaceutical companies for potential use in cancer chemotherapy. Since the molecular circuitry and biological read-outs of this pathway differ significantly between cell types, detailed mechanistic studies are critical for evaluating the PI3K network as a target for chemotherapy in pancreatic cancer. We have developed genetic systems to elucidate the signal transduction components that contribute to the transformed state of pancreatic cancer and to evaluate potential components for therapeutic intervention. The therapeutic application of PI3K/AKT inhibitors would be enhanced by information about the activation status of the pathway prior to, and following treatment. In this regard, we are collaborating with the MGH Center for Molecular Imaging in the development and testing of approaches to assess PI3K/AKT activity in vivo.

■Dr. Jordan D. Berlin
Dr. Jordan D. Berlin is a medical oncologist who specializes in gastrointestinal cancers such as malignancies of the colon, rectum, anus, esophagus, stomach, small intestine, liver, gallbladder, pancreas and bile ducts. His clinical research efforts focus on novel treatment approaches. Dr. Berlin believes in enrolling patients, when possible, on clinical trials to learn more about the best and safest ways to treat gastrointestional cancers. Improving treatments, while preserving the patient’s ability to function normally, are among Dr. Berlin’s goals.

As Director of the Clinical Gastrointestinal Program, he works with a multidisciplinary team that includes surgeons and radiation oncologists to improve cure rates and develop a treatment plan specific for each patient. Dr. Berlin serves on a number of national advisory committees, is an editorial board member for the International Journal of GI Cancer and is Editor-in-Chief for Colorectal Cancer Index and Reviews.

■Dr. Theresa A Brentnall

Theresa A Brentnall, MD University of Washington School of Medicine

Current Research Interests
Tumorigenesis in the gastrointestinal tract with emphasis on 3 research areas:

1. Molecular events an dearly detection of pancreatic cancer
2. Surveillance and management of patients who inherit pancreatic cancer
3. Molecular events, prevention, and early detection of colon cancer in patients with inflammatory bowel disease

■Dr. Donald J. Buchsbaum
Dr. Donald J. Buchsbaum was born in New York City in March 1945. In 1972 he received his Ph.D. in Biophysics-Immunology from the University of Rochester. Before coming to UAB in 1990, he was an Assistant Professor at the University of Michigan and the University of Minnesota. He has secondary appointments in the Departments of Pharmacology and Surgery.

The Comprehensive Cancer Center and the Department of Radiation Oncology established the Division of Radiation Biology in October, 1990. Donald J. Buchsbaum, Ph.D. was recruited from the University of Michigan to be the Division Director and develop an experimental radioimmunotherapy program using radiolabeled antibodies that bind to antigens expressed on the surface of cancer cells. The Division has grown to include 4 additional Ph.D. faculty, 3 postdoctoral fellows, and technicians totaling 25 full-time employees. The Division has developed innovative approaches to radioimmunotherapy of cancer using novel targeting molecules. This research has contributed to the funding of Ovarian and Breast Cancer Specialized Programs of Research Excellence (SPORE) at UAB by the National Cancer Institute, and funding to the Cancer Center from the Avon Products Research Foundation for breast cancer research. In addition, the Division of Radiation Biology has been in the forefront of research into the treatment of cancer in exp erimental models with a combination of gene therapy and radiation therapy. This has resulted in a SPORE in Brain Cancer and grants and contracts from the National Cancer Institute, the Department of Energy, and the Department of Defense, with emphasis on colon, ovarian, and prostate cancer. Another significant finding was unlabeled antibody against epidermal growth factor receptor resulted in increased sensitivity of head and neck cancer to radiation. This was translated into a very successful clinical phase I trial in head and neck cancer at UAB. A phase III trial testing this new combination therapy with UAB as the lead institution showed significantly increased local tumor control and survival in patients with head and neck cancer. Recently he has been investigating the treatment of breast, colon, lung, pancreatic, and brain cancer with death receptor antibodies in combination with chemotherapy and radiation therapy with very promising results. This has resulted in funding of a Pancreatic SPORE. Thus, very innovative and clinically relevant research is being carried out in the Division of Radiation Biology.

■Dr. Chaity Chaudhury
Dr. Chaity Chaudhury is a post-doctoral researcher in the laboratory of Doug Hanahan at University of California, San Francisco.

Her work focus is on elucidating the role of Cathepsins on the tumor and its microenvironment in a mouse model of pancreatic ductal adenocarcinoma using both pharmacological and genetic approaches to ablate these enzymes. She plans to evaluate parameters such as tumor proliferation, apoptosis, neoangiogenesis, immune infiltration, stromal response and tumor metastasis. These studies will further knowledge of mechanism and potentially have important implications for pancreatic cancer therapy, where there is a huge unmet need for better therapies. In addition, she is exploring the possibility of exploiting the abundant expression of these enzymes as potential imaging targets for pancreatic cancer, imaging for early diagnosis of these tumors.

A biochemist by training Dr. Chaudhury graduated from The Ohio State University, Columbus, OH with a Ph.D. in Biochemistry from the laboratory of Clark Anderson where she worked on nonclassical MHC-I molecules and spearheaded the discovery of albumin as a novel ligand for MHC-related Fc receptor for IgG (FcRn). After completing her graduate work on FcRn, she continued for a short while in the Anderson laboratory focusing on HFE another nonclassical MHC-I molecule implicated in hereditary hemochromatosis (HH). This work using several targeted gene knockout mouse models showed that lower serum transferrin concentration seen in HH is caused due to increased transferrin saturation resulting in rapid degradation of transferrin as a result of HFE-deficiency.

■Dr. Ru Chen

Dr. Ru Chen received her PhD from University of Washington, and had post-doctoral training at the University of Washington and Institute for Systems Biology. She is a research assistant professor at the University of Washington. Dr. Chen’s research interest is applying proteomics to study cancer progression, and identify biomarkers for early detection of pancreatic cancer.

■Dr. Jeffrey Clark
Associate Professor, Department of Medicine, Harvard Medical School
Director, Clinical Trials Support, Dana-Farber Cancer Institute
Medical Director of Clinical Trials, MGH Cancer Center, Massachusetts General Hospital
Medical Director of the Clinical Trials Core, Dana-Farber/Partners, Dana-Farber Cancer Institute

DF/HCC Program Affiliation
Member, Translational Pharmacology and Early Therapeutic Trials Program
Member, Gastrointestinal Malignancies Program
DF/HCC Associations
Acting Director, Clinical Research Support
Clinical Trials Support, Associate Director
Director, Protocol Review and Monitoring System Core
Member, Center Scientific Council
Research Abstract
The major area of my research focus is in the evaluation of new agents and approaches in phase I, pilot and early phase II trials. This includes the evaluation of pharmacokinetics and biological correlates of the activity of these agents or approaches. I am especially interested in the development of new theraputic approaches for gastrointestestional malignancies. I have an interest in designing and implementing systems to improve the quality and performance of clinical trials. This includes the development and utlization of computerized systems whenever possible.

■Dr. Adrienne D. Cox

Associate Professor
Department of Radiation Oncology
Ph.D., Biomedical Sciences
Eastern Virginia Medical School
Research Interests:
• Lipid modification
• Signal transduction
• Protein function of Ras family oncogenes
Research Synopsis:
Molecular mechanisms of cancer biology: Our lab is interested in molecular mechanisms of cancer biology, particularly concerning members of the Ras superfamily of proteins. Ras proteins are the prototypes for a large superfamily of related small GTPases whose activity is regulated by a cycle of GTP/GDP binding and subcellular localization, and whose diverse functions in cellular physiology include growth, invasion, motility, cell cycle control, differentiation and death. Whereas normal signal transduction by Ras family proteins is required for proper cell growth and differentiation resulting from a wide variety of different inputs, their malfunction or deregulated activity is linked to uncontrolled cell proliferation or inappropriate cell suicide. Indeed, mutated Ras genes are the most commonly mutated oncogenes in human cancer, and their deregulated function as a consequence of alterations in other proteins is also a critical mechanism driving many cancer cells. In our lab, studying the mechanisms whereby mammalian Ras family proteins and their cousins control the conversion of extracellular signals to intracellular responses provides us with several broad areas of experimentation with both basic science and translational bents.
• Location location location: where small GTPases go and why
• Disruption of lipid modifications for cancer treatment
• Ras and Rho family GTPases: why so many?
• Radiation responsiveness: control of death, arrest or survival

■Dr. Channing J. Der
Dr. Channing J. Der, Kenan Professor, Ph.D., Microbiology, University of California, Irvine. Dr. Der’s Research Synopsis: The broad goal of our research is to delineate the molecular basis for cancer. One major emphasis of our studies is the study of Ras oncoproteins, which are key regulators of signal transduction pathways that control normal cell growth and differentiation. Mutated Ras proteins are found in 30% of human cancers and promote cancer cell growth, invasion, and metastasis. We are evaluating how aberrant Ras proteins alter the regulation of cell cycle progression, programmed cell death, and gene expression to promote oncogen sxdsxdesis. One facet of these studies involves a dissection of the complex signaling mechanisms that are deregulated by Ras in cancer cells, including the Raf-MEK-ERK mitogen-activated protein kinase cascade. A long-term goal of these studies is to use this information for the development of anti-Ras drugs as novel approaches for cancer treatment (e.g., farnesyltransferase and kinase inhibitors). Another major aspect of our studies involves the study of Ras-related proteins. The human Ras proteins are but a small branch of a larger superfamily of Ras-related GTPases. While Ras proteins are mediators of positive growth regulation, Ras-related proteins control a range of diverse cellular processes that include actin cytoskeletal organization ( Rho proteins) and negative growth regulation (DBC2, Rerg, NOEY2). A major goal of our studies has been to determine whether the aberrant activities of Ras-related proteins also contribute to malignant transformation. In particular, we have focused on the study of Rho family small GTPases, regulators of actin cytoskeletal organization and gene expression, and mediators of tumor cell invasion and metastasis. We utilize human cell culture and mouse models, as well as genetic studies in C. elegans to study mechanisms of signal transduction. Our studies focus on the role of aberrant signaling in the development and growth of cancers of the breast, ovary, pancreas, colon, lung and skin.

■Dr. Ronald M. Evans

Dr. Ronald M. Evans, a professor in the Gene Expression Laboratory, is the March of Dimes Chair in Developmental and Molecular Biology. Evans is an authority on hormones, both their normal activities and their roles in disease. A major achievement in Evans’ lab was the discovery of a large family of molecules, named receptors, that respond to various steroid hormones, Vitamin A and thyroid hormones. These hormones help control sugar, salt, calcium and fat metabolism; thus, they impact on our daily health as well as treatment of disease. The receptors Evans discovered are primary targets in the treatment of breast cancer, prostate cancer and leukemia, as well as osteoporosis and asthma. In addition, Evans’ studies led to a new hormone that appears to be the molecular trigger controlling the formation of fat cells. This hormone and its chemical derivatives represent one of the newest and most important advances in understanding problems arising from excess weight and obesity and the potential treatment of adult onset diabetes (Type II diabetes).

■Dr. Toru Furukawa
Dr. Toru Furukawa is an Associate Professor of International Research and Educational Institute for Integrated Medical Sciences at Tokyo Women’s Medical University, Tokyo, Japan. He graduated Faculty of Medicine, Akita University, Akita, Japan, in 1986 and did his surgical residency and a fellowship in gastroenterological surgery at Tohoku University Hospital, and his doctoral research at Department of Pathology, Research Institute for Tuberculosis and Cancer, Tohoku University, Sendai, Japan. He received his Doctor of Philosophy from Tohoku University in 1993. He did his postdoctoral research at Montreal General Hospital Research Institute, Montreal, PQ, Canada from 1993-95. He was an Assistant Professor in the First Department of Pathology, Tohoku University School of Medicine from 1996-2005. He received a number of awards including Government of Canada Award (1994) and Pathology Research Award from the Japanese Society of Pathology (2002). His research interests include the molecular mechanisms of pancreatic carcinogenesis. His current research is focusing on identification of molecular targets for curing the pancreatic cancer.

■Dr. Michael Goggins
Dr. Michael Goggins is a 1988 graduate of the University of Dublin, Trinity College. He did his internal medicine residency and a fellowship in gastroenterology in St. James’ hospital, Dublin. He was a Lecturer in Medicine in Trinity College from 1992-1995. He obtained his Membership of the Royal College of Physicians of Ireland in 1991 and his European Diploma in Gastroenterology in 1995. The subject of his MD thesis was the characterization of protein methylation in postmortem human brain. He is Director of the Pancreatic Cancer Early Detection Laboratory at The Johns Hopkins Medical Institutions. His research interests include the molecular genetics of pancreas cancer. Areas of particular interest include the role of germline BRCA2 mutations in pancreas cancer and characterizing the molecular genetic progression model for pancreas cancer.

■Dr. William Hawkins
Dr. William Hawkins
Current Position
Assistant Professor, Surgery
Division of General Surgery
Hepatobiliary-Pancreatic and Gastrointestinal Surgery Section

Specialty Areas
Gallbladder Surgery
Gastrointestinal Oncology
Liver Surgery
Pancreatic Surgery
Biliary Surgery
Hepatobiliary Pancreatic Cancer
Hepatobiliary Pancreatic (HPB) Surgery
Areas of Clinical Interest
Minimally invasive foregut and solid organ surgery, pancreatic cancer, liver cancer, sarcoma, abdominal wall hernia, and biliary tract disease, hepatocellular cancer, hepatoma, gastric cancer, revision surgery
Areas of Research Interest
Tumor immunology
Board Certification
Medical Education
B.S.: Biology, State University of New York at Stony Brook, Stony Brook, New York, 1991
Medical Degree: State University of New York at Stony Brook, School of Medicine, Stony Brook, New York, 1995
Residency: Surgery, Beth Israel Deaconess Medical Center, Boston, Massachusetts, 1998
Research Fellowship: Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York, 2000
Residency: Surgery, Massachusetts General Hospital, Boston, Massachusetts, 2001
Chief Residency: Surgery, Massachusetts General Hospital, Boston, Massachusetts, 2002
Fellowship: Surgical Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York, 2004
Hospital Affiliations
Barnes Jewish Hospital

■Dr. Aram F. Hezel

Education: MD Degree: State University of New York at Buffalo School of Medicine, Buffalo, NY, 2000
Postdoctoral Training
Residency: Internal Medicine: Beth Israel Deaconess Medical Center, Boston, MA
Fellowship: Medical Oncology, Dana-Farber/Partners Cancer Care, Boston, MA
Board Certification
American Board of Internal Medicine, 2003
Medical Oncology, 2005
Hospital Appointments
Assistant in Medicine Hematology and Medical Oncology

■Dr. Sunil Hingorani

Research Interests: To answer fundamental questions about the biology of pancreas cancer, our laboratory has turned to the use of genetically engineered mouse models. By directing the expression of key mutations in specific oncogenes and tumor suppressor genes to the mouse pancreas, we have developed models that faithfully mimic the spectrum of human pancreatic ductal adenocarcinoma (PDA) from its earliest preinvasive lesions to locally invasive and widely metastatic disease. Our goals are to use these models to reveal basic mechanisms of disease pathogenesis, as well as to serve as platforms for the design and testing of strategies for early detection and for treatment and chemoprevention.

Three broad areas of inquiry are currently being pursued: 1) continuing investigations into the molecular requirements for disease progression and their respective impact on the resultant clinical and biological phenotype; 2) investigations into the cell-of-origin for preinvasive and invasive ductal carcinoma and the possibility that it may represent a mutated tissue progenitor cell; 3) efforts to identify biomarkers of early disease and markers associated with disease response and resistance to therapy.

■Dr. Michael Hollingsworth
Dr. Michael Hollingsworth is a Professor at the University of Nebraska Eppley Institute, Department of Biochemistry and Molecular Biology. The general subject of research in his laboratory is pancreatic cancer and other diseases of the pancreas (primarily pancreatitis and cystic fibrosis). They have used modern techniques to molecular biology, biochemistry, cell biology, and immunology to develop a comprehensive program of investigation into the biology of normal and diseased pancreatic ductal epithelial cells.

Several of the main projects in the laboratory center around the study of a complex mucin-like glycoprotein, MUC1, which is believed to play an important role in the normal function of pancreatic ductal epithelia and in the pathogenesis of pancreatic diseases, such as pancreatic adenocarcinoma. The team uses usesthe techniques of molecular and cellular biology to examine the regulation of expression and the mechanisms of post-translational processing of MUC1 in tumor cells and other disease conditions as compared to their normal cell counterparts. These studies also provide a paradigm to study basic aspects of the post-translational process (particularly O-glycosylation). They are developing and characterizing new monoclonal antibodies and tumor vaccine reagents for diagnostic and therapeutic uses that target known tumor associated antigens found on mucins. They are also studying the MUC1 promoter.

Dr. Hollingsworth has received funding by the National Cancer Institute (NCI) as PI of a Biomarker Developmental Laboratory (organ focus Pancreas) within the Early Detection Research Network (EDRN). Biomarker Developmental Laboratories have the responsibility for the development and characterization of new biomarkers or the refinement of existing biomarkers.

Other projects in the lab involve the application of different cDNA cloning techniques to identify genes and their encoded proteins that are important to the process of development and differentiation of normal ductal cells in the human pancreas, and which may contribute to the pathogenesis of different diseases.

■Dr. Ralph H. Hruban

Dr. Ralph H. Hruban is a Professor of Pathology and Oncology at The Johns Hopkins University School of Medicine. He received his Doctor of Medicine from The Johns Hopkins University. He continued at Johns Hopkins for his residency training, spent one year as a Fellow at Memorial Sloan-Kettering Cancer Center in New York, and then returned to Johns Hopkins to join the Faculty in 1990. He established the National Familial Tumor Registry January 1, 1994.

Dr. Hruban is currently the Director of The Sol Goldman Pancreatic Cancer Research Center, and Director of the Division of Gastrointestinal/Liver Pathology. Dr. Hruban has written over 400 scientific papers, 80 book chapters and reviews, and three books. He is recognized by the Institute for Scientific Information as a Highly Cited Researcher and by Essential Science Indicators as the most highly cited pancreatic cancer scientist - designations given to the most highly influential scientists. In addition to his research efforts, he helped create the Johns Hopkins Pancreatic Cancer Web Page, Dr. Hruban has received a number of awards including the Arthur Purdy Stout Prize for significant career achievements in surgical pathology, the Young Investigator Award from the United States and Canadian Academy of Pathology, the PanCAN Medical Visionary Award, and five teaching awards from the Johns Hopkins School of Medicine. Dr. Hruban is a member of the Scientific Advisory Board of PanCAN, The Joseph C. Monastra Foundation and The Michael Rolfe Pancreatic Cancer Foundation, and the Director of Science for The Lustgarten Foundation.

■Dr. Tony Hunter
Dr. Tony Hunter is an American Cancer Society Research Professor and director of the Molecular and Cell Biology Laboratory at the Salk Institute for Biological Studies. He is also an adjunct professor in the Division of Biological Sciences at the University of California at San Diego. His research is focused on how cells regulate their growth and division, and how mutations in genes that regulate growth lead to cancer.
In 1979, his lab discovered that a phosphate can be attached to tyrosine residues in proteins, a discovery that enabled researchers to study tyrosine kinases and their functions in signal transduction, cell growth and development, and cancer and other diseases. Dr. Hunter’s and Dr. Pawson’s work has led to the development of drugs for halting cancer cell proliferation and has potential for other significant therapies.
Dr. Hunter’s current research interests include the tyrosine kinases of the Src and growth factor receptor families, as well as the signaling pathways downstream of these tyrosine kinases that regulate cell growth, cell migration and differentiation. His group also studies the cyclin-dependent protein kinases and other protein kinases that regulate progression through the cell cycle, how protein ubiquitination and degradation is used as a means of regulating signaling pathways and the cell cycle, and protein trafficking.
He is on the editorial boards of several journals, including Cell, Molecular Cell, the EMBO Journal and the Proceedings of the National Academy of Sciences and has received many awards for his research, including a National Cancer Institute Outstanding Investigator Award.
He is a Fellow of the Royal Society of London, an Associate Member of the European Molecular Biology Organization (EMBO), a Fellow of the American Academy of Arts and Sciences, a Foreign Associate of the National Academy of Sciences, and a Member of the Institute of Medicine. He received his Ph.D. in biochemistry from the University of Cambridge, England, for his research on mammalian protein synthesis.

■Dr. William Isacoff

Dr. William Isacoff was born in Brooklyn, New York and raised on Long Island, where he received his undergraduate degree from Hofstra University. In 1970, he received his Medical Degree from New York Medical College. After completing his fellowship training in Hematology/Oncology at UCLA-Harbor General in Torrance California, he began his research and teaching career at the UCLA-Harbor General Hospital, accepting the position as Associate Chief of Medical Oncology, which he held until 1980. He did pioneering research on the Biochemical Pharmacology of Methotrexate, thus leading to the safe use of high dose treatment formulations for patients with Osteogenic Sarcoma. This work led to the effective disease control that enabled patients to be cured without amputation. From 1975 to 1981 he was a Senior Consultant to the Rand Corporation in Santa Monica.
Currently Dr. Isacoff holds an Academic Appointment within the Department of Medicine at the UCLA David Geffen School of Medicine, and serves on the Board of Directors of the Jonsson Comprehensive Cancer Center Foundation. His current research interests focus on new treatment development for Pancreatic Cancer, and has been a principle investigator and consultant to The Southwest Oncology Group, and The American College of Surgeons Oncology Group. In 2005, he was the recipient of the Medical Visionary Award from the Pancreatic Cancer Action Network, a national patient advocacy organization. He is as a member of the Board of Governors of the Hebrew University.

■Dr. Andrew H. Ko
Dr. Andrew H. Ko is a specialist in gastrointestinal cancer, with a particular interest in pancreatic cancer. Ko is interested in the development of new treatment strategies, including molecularly targeted therapies, for patients with gastrointestinal malignancies.
He earned an undergraduate degree in applied mathematics and biology at Brown University and a medical degree at Johns Hopkins School of Medicine. After an internship and residency at Beth Israel Hospital in Boston, he completed a fellowship in medical oncology at Stanford University before joining UCSF Medical Center in 2001.
• Esophageal Cancer
• Gastrointestinal Cancer
• Liver Cancer
Johns Hopkins University (1995)

Beth Israel Hospital-Boston, MA – Internal Medicine (1998)

Stanford University Medical Center (2001)

■Dr. Murray Korc
Dr. Murray Korc completed his undergraduate studies at Brooklyn College in 1968, majoring in Biology. He received his medical degree in 1974 from Albany Medical College. In 1977, he completed a residency in internal medicine at Albany Medical Center. In 1979, he completed training in endocrinology, diabetes and metabolism at University of California, San Francisco. He also completed three years of postdoctoral training at the same Institution in 1981. He then joined the faculty of the Department of Medicine at the University of Arizona in Tucson as an assistant professor. In 1985 be became an associate professor, with joint appointments in Medicine and Biochemistry at that Institution. In 1989 he moved to UC Irvine to become the Chief of the Division of Endocrinology, Diabetes and Metabolism, and Professor of Medicine and Biological Chemistry. He was also a member of the UC Irvine Cancer Center, and a Program Leader in Growth Factor Signaling at the Cancer Center. In 1996 he also received an appointment in the Department of Pharmacology at that Institution. In 2003, Dr. Korc joined the faculty at Dartmouth as Professor and Chair of Medicine and Professor of Pharmacology and Toxicology.

■Dr. Daniel Laheru

Dr. Daniel Laheru specializes in gastrointestinal oncology with a specific focus on pancreatic cancer. His clinical research interests are in developing and testing new therapies for the treatment of pancreatic cancer. In collaboration with Elizabeth Jaffee, M.D., he has initiated clinical studies to optimize a vaccine approach using GM-CSF transfected pancreatic cell lines as a vaccine in two distinct patient populations. First, the vaccine has been integrated with chemotherapy and radiation therapy in patients with resected pancreatic cancer who are at risk for disease recurrence. Second, the vaccine will soon be tested integrated with novel molecular targeted drugs such as Erbitux and anti-CTLA-4 antibody or with immune modulating doses of Cytoxan in patients with metastatic pancreatic cancer. He has also incorporated correlative studies that should provide important information to better understand optimal vaccine-boosting schedules as well as to identify antigens that can be predictive of in-vitro markers for anti-tumor immune responses. Data generated from this proposed study could serve as the foundation for the development of novel new antigen specific vaccines for pancreatic cancer. His work in pancreatic cancer vaccines has been funded by an NIH K23 Mentored Patient-Oriented Research Career Development Award.
In collaboration with Dr. Christine Iacobuzio-Donahue, he is investigating mechanisms of chemotherapy resistance in pancreatic cancer. In collaboration with Drs. Ross Donehower, Manuel Hidalgo, Wells Messersmith, Ralph Hruban, and Scott Kern, he will be developing and testing new targets for therapy in patients with metastatic pancreas cancer.

■Dr. Brian Lewis
Academic Role: Assistant Professor
Faculty Appointment(s) In:
Program in Gene Function and Expression
Program in Molecular Medicine
Other Affiliation(s):
Graduate Program in Cancer Biology
Interdisciplinary Graduate Program
Academic Background
Brian Lewis received his B.S. in Biology from the University of California, Los Angeles in 1991, and his Ph.D. from Johns Hopkins University in 1997. He performed postdoctoral studies at the NIH and Memorial Sloan-Kettering Cancer Center, supported by a Helen Hay Whitney Foundation postdoctoral fellowship. He is currently supported by a Burroughs Wellcome Fund Career Development Award in the Biomedical Sciences. Dr. Lewis joined the Program in Gene Function and Expression at the University of Massachusetts Medical School as an Assistant Professor in the winter of 2003.

■Dr. Steven D. Leach
Dr. Steven D. Leach is the Paul K. Neumann Professor in Pancreatic Cancer, Chief of the Division of Surgical Oncology, and Director of Research in the Department of Surgery at Johns Hopkins. Dr. Leach received his undergraduate degree in Biology at Princeton University, followed by his M.D. degree at Emory. He subsequently completed training in Surgery and Cell Biology at Yale, as well as a fellowship in Surgical Oncology at the University of Texas M.D. Anderson Cancer Center. Dr. Leach directs an NIH-funded research program focused on epithelial differentiation in exocrine pancreas, using both mouse and zebrafish model systems. This work is based on the general hypothesis that pancreatic cancer may be initiated by characteristic changes in epithelial differentiation. By elucidating the molecular mechanisms regulating exocrine differentiation in developing pancreas, Dr. Leach’s lab has provided important new insights regarding abnormal differentiation events occurring during pancreatic tumorigenesis. His work has demonstrated critical links between early forms of pancreatic cancer and the epithelium of the embryonic pancreas, providing exciting new strategies for disease detection and chemoprevention.
Dr. Leach recently joined the Johns Hopkins Departments of Surgery and Oncology as the first Paul K. Neumann Professor in Pancreatic Cancer.

■Dr. Craig D. Logsdon
Dr. Craig D. Logsdon is at UT M. D. Anderson Cancer Center, Cancer Biology. Dr. Logsdon’s Research Interests: Pancreatic disease; biomarker discovery; cancer cell biology; molecular biology; gene therapy; inflammation

The goal of my laboratory is to improve the diagnosis and treatment of pancreatic cancer and the related disease pancreatitis. The strategy we employ involves several steps: 1) Discovery; 2) Functional Characterization; and, 3) Experimental therapeutic application.

Discovery is the process of identifying the molecules specifically expressed in the disease state. We have utilized gene profiling and proteomics approaches to identify disease specific molecules. Functional characterization is carried out in order to identify molecules with high potential for translational value such as those involved in cancer cell proliferation and survival. Validation of functional roles is conducted in vitro and then in vivo. Molecules that function to increase the aggressiveness of pancreatic cancer are deemed good targets for therapeutic intervention. Experimental therapeutic applications are initiated using reagents developed or identified for manipulation of these molecules during functional assessment. Antibodies, dominant negatives, siRNAs and pharmacological agents capable of manipulating the function of the molecules can then be tested as potential therapeutic agents in animal models. Currently, we are using orthotopically transplanted pancreatic tumors in immune deficient animals. We are also developing genetic animal models for pancreatic cancer for these types of studies.

■Dr. Margaret T. Mandelson
Dr. Margaret T. Mandelson, holds dual appointments at the Fred Hutchinson Cancer Research Center and the Group Health Cooperative Center for Health Studies, Seattle, WA.

Dr. Mandelson is a cancer epidemiologist with interests in the natural history and etiology of breast and gastrointestinal cancers. Her research includes studies of cancer screening and control and the identification of biologic markers of cancer risk and prognosis. She serves as a member of the Scientific Advisory Board for PanCAN.
Dr. Mandelson received her PhD from the University of Washington (1994) in Epidemiology and MPH from Boston University (1985) in Epidemiology.

■Dr. Kenoki Ohuchida
Dr. Kenoki Ohuchida, is an academic researcher, Assistant Professor, MD, PhD, within the Department of Surgery and Oncology at Kyushu University in Fukuoka, Japan.

He is interested in the roles of cancer stem cells and tumor-stromal interaction in pancreatic cancer progression and carcinogenesis.

■Dr. Jerrold Olefsky

Dr. Jerrold Olefsky, University of California, San Diego
My research program is divided into clinical investigation and basic research components. Clinical investigation approaches include studies aimed at identifying in vivo mechanisms underlying the pathogenesis of non-insulin dependent diabetes mellitus, obesity, and other disorders of insulin resistance. Studies are in progress to identify the relative role of each organ system (muscle, liver and fat) to the pathophysiology of NIDDM. In addition, a number of protocols are underway exploring new modes of therapy for established NIDDM as well as means of primary prevention for this disease. A major focus for the basic research program is to understand the molecular and cellular mechanisms of insulin and IGF-I action. An important emphasis is placed on understanding the structure/function relationship of the cognate receptors for these ligands. Approaches used include the use of site directed mutagenesis to modify the insulin and/or IGF-I receptor cDNAs followed by transfection of these modified cDNAs into host mammalian cells for biologic studies. Several functional domains of these receptor proteins have been identified which mediate the divergent and convergent signaling pathway of these two hormone receptor systems. For example, a domain of the insulin receptor has been identified which mediates the metabolic signaling properties of this receptor, whereas the other biologic effects of this receptor are intrinsic to other domains. The downstream signaling pathways of thee receptors are also under intensive investigation. These include studies of the mechanisms whereby insulin and IGF-I stimulate transcription of a series of early response genes and what are the signaling molecules which lie between the receptor and the DNA response elements which mediate these signaling pathways.

■Dr. Gloria Petersen

Dr. Gloria Petersen holds appointments in the departments of Health Science Research, Gastroenterology, and Medical Genetics. She is Professor of Epidemiology, Mayo Clinic College of Medicine. She is also certified by the American Board of Medical Genetics as a PhD Medical Geneticist.
Dr. Petersen's research interests and expertise are in the application of genetic epidemiology to cancer etiology, including genetic linkage analysis of cancer families for gene discovery, and genetic association studies for characterizing gene-environment interaction. Her research focus is particularly on applying genetic epidemiologic methods to colorectal and pancreatic cancers. She is also interested in translating gene discoveries into clinical application, with respect to improving risk assessment through modeling and studying impact of genetic testing. Dr. Petersen's funded research programs are primarily an R01 for the Pancreatic Cancer Genetic Epidemiology Consortium, in which she directs an eight-center consortium that is prospectively recruiting high risk familial pancreatic cancer kindreds and genotyping them to localize the chromosomal regions that harbor susceptibility loci, and identification of the gene(s) themselves. We have developed a resource of over 1300 families for study. Dr. Petersen also directs the SPORE in Pancreatic Cancer and has a project to study the molecular epidemiology of pancreatic cancer. We will be genotyping 1200 cases and 1200 controls for candidate SNPs to study genetic risk and gene-environment interactions.

■Dr. Howard A. Reber

Dr. Howard A. Reber was born and raised in Philadelphia, PA, where he also received his medical education and surgical training at the University of Pennsylvania. His clinical and research interests in pancreatic cancer and other pancreatic diseases date to that time. Since he finished his formal education in 1970, he has held academic appointments in a number of institutions including the University of California at San Francisco, the University of Missouri in Colombia, and the University of California at Los Angeles. At UCLA, he is Professor of Surgery, Chief of Gastrointestinal Surgery and Director of the Ronald S. Hirshberg Pancreatic Cancer Research Laboratory.

Dr. Reber has an international reputation and is an acknowledged authority in pancreatic physiology and disease. He is widely sought after as a lecturer and visiting professor. He has written and edited a number of major textbooks and chapters on pancreatic diseases, especially pancreatic cancer. He is a coauthor of the current state of the art recommendations for the diagnosis and management of pancreatic cancer in the United States (Di Magno E, Reber HA, Tempero M. America Gastroenterological Association Medical Position Statement: Epidemiology, Diagnosis and Treatment of Pancreatic Ductal Adenocarcinoma and AGA Technical Review. Gastroenterology 1999;117:1463-1484). His research publications are in excess of 400 articles, abstracts and chapters. He is a past president of the American Pancreatic Association and currently serves as its Executive Secretary and Treasurer. And he is the CoChair (with John Cameron, MD) of the Pancreas Section of the American College of Surgeons Oncology Group.

■Dr. Neal Rosen

The main goal of our laboratory is the identification and characterization of signal transduction pathways that cause the dysregulation of growth and inhibition of apoptosis that characterize advanced human cancer. Our laboratory is dedicated to understanding the consequences of activation of these pathways and to using this information to develop mechanism-based therapeutic strategies.
A major focus is the evaluation of Hsp90 as a therapeutic target in cancer patients. Hsp90 is a cellular chaperone that is required for maintaining the proper conformation of several important signaling proteins, including transmembrane tyrosine kinases and steroid receptors. The laboratory is studying the role of Hsp90 family members in maintaining the transformed phenotype of cancer cells. The knowledge gained is being used to develop strategies for using Hsp90 inhibitors in patients. A lead compound, the ansamycin 17-AAG, is currently in clinical trial at MSKCC. The laboratory has developed, and is currently evaluating, second generation ansamycins and small-molecule inhibitors with potentially greater selectivity and more favorable pharmacologic properties. (See ansamycin and small-molecule inhibitor projects.)
In addition, the laboratory is studying kinase inhibitors that target EGFR, HER2, MEK, src, mTOR, Met, and small molecules that inhibit androgen receptor and estrogen receptor. These compounds are being used as re-agents to define the role of these pathways in tumor cells with the goal of developing strategies for using these agents in patients. (See kinase inhibitor project.)

■Dr. Mace Rothenberg
Dr. Mace Rothenberg is a medical oncologist who specializes in Phase I drug development and clinical trial design with an emphasis in gastrointestinal cancers (particularly colorectal and pancreatic). His research focuses on evaluating new drugs in humans from a clinical, pharmacologic, biologic and genetic perspective. He studies novel cancer therapeutic agents to determine their safety and clinical application and his most significant contributions have been in the development and FDA approval of drug treatments for colorectal and pancreatic cancer.
Dr. Rothenberg is recognized nationally and internationally as an expert on clinical trial design and evaluating new treatments. Vanderbilt is one of only 16 institutions designated and funded by the National Cancer Institute (NCI) as a Phase I Center. Several of Dr. Rothenberg's studies focus on investigational drugs for patients with advanced cancers for which there is no known effective or curative therapy. He is recognized nationally and internationally for his work, serves on a number of advisory committees, and is an editorial board member for numerous publications including Clinical Cancer Research, Clinical Colorectal Cancer and Investigational New Drugs, and The Journal of New Anticancer Agents.
Research Specialty
Early stage clinical, pharmacologic, pharmcogenetic, and biological evaluation of new anticancer agents

Research Description
Mace L. Rothenberg, M.D. is Professor of Medicine at the Vanderbilt University Medical Center and Ingram Professor of Cancer Research at the Vanderbilt-Ingram Cancer Center.
A 1982 graduate of New York University School of Medicine, Dr. Rothenberg trained as an Intern and Resident in Internal Medicine at Vanderbilt University from 1982-85. He obtained his medical oncology training at the National Cancer Institute from 1985-88 and served as Special Assistant to the Director, Division of Cancer Treatment from 1988-91. In 1991, he moved to San Antonio where he was appointed Assistant, then Associate Professor in the Department of Medicine, Division of Medical Oncology at the University of Texas Health Science Center in San Antonio and Executive Officer of the Southwest Oncology Group. In 1998, Dr. Rothenberg returned to Vanderbilt where he is currently Professor of Medicine, Ingram Professor of Cancer Research, Director of Phase I Drug Development, Co-Leader of the Experimental Therapeutics Program, and Director of Clinical and Translational Research for the Vanderbilt SPORE in Gastrointestinal Cancer.
Dr. Rothenberg has published more than 100 articles and book chapters, primarily in the areas of early stage drug development, gastrointestinal malignancies, and ovarian cancer. He serves on the editorial boards of several leading medical journals, including the Journal of Clinical Oncology, Clinical Cancer Research, Investigational New Drugs, Cancer Chemotherapy and Pharmacology, and Clinical Colorectal Cancer. Dr. Rothenberg?s research focuses on the evaluation of new drugs in humans from clinical, pharmacologic, biologic, and genetic perspectives. His work was critical to the development, and eventual FDA approval, of irinotecan (CPT-11, Camptosar) in 1996 and oxaliplatin (Eloxatin) in 2002 for colorectal cancer and gemcitabine (Gemzar) in 1996 for pancreatic cancer.

■Dr. Ashok K. Saluja
Vice Chair of Research
Department of Surgery
Physiology and Cell Biology of Pancreas: Stimulus-Secretion Coupling (intracellular signal transduction).

Etiology and Pathophysiology of Acute and Chronic Pancreatitis in Animal Models.
Mechanisms of premature intra-acinar cell activation of digestive enzyme zymogens.
Alterations of intracellular calcium homeostasis in pancreatitis and pancreatic cancer.
Role of Inflammatory agents in determining the severity of pancreatitis.
Relationship between pancreatitis and lung injury.
Role of Protease Activated Receptors (PARs) in pancreatitis.
Heat shock proteins and their role in pancreatitis: How do HSPs prevent pancreatitis?
Pathophysiology of alcohol-induced pancreatic injury.
Role of heat shock proteins in pancreatic cancer.

■Dr. C. Max Schmidt
Assistant Professor, Surgery
Assistant Professor, Biochemistry and Molecular Biology
Assistant Member of the Walther Oncology Center

Description and summary of research focus of the laboratory:
Hepatocellular carcinoma (HCC) is the commonest cause of solid organ cancer mortality in the world. Aside from a small percentage of patients who can be cured with surgery, no effective treatment options exist. In addition, the incidence and prevalence of HCC is steadily increasing in large part due to the Hepatitis C pandemic which infects an estimated 170 million persons worldwide, five times as widespread as HIV. Our research efforts are focused on improved therapeutic options for this tumor through a greater understanding of its growth and survival mechanisms. Multiple studies from our laboratory provide compelling evidence that aberrant overexpression (or disinhibition) of the mitogen activated protein kinase (MAPK) signaling cascade is responsible for HCC cells acquiring the proliferative phenotype (uncontrolled growth). The MAPK signaling cascade is a series of phosphorylation reactions which results in the regulation of genes responsible for growth and survival of the cell. We have discovered alterations of MAPK intermediates in human HCC in vivo, and have linked these to functional growth pathways through MAPK signaling in vitro. Our laboratory investigations are directed at understanding the mechanisms of MAPK mediated growth in HCC and testing whether targeting MAPK will be an effective chemotherapeutic and chemopreventative strategy.
Pancreatic adenocarcinoma is an equally deadly cancer. Incidence rates match mortality rates. Like in HCC, surgery offers the only hope for cure. Preliminary studies from our laboratory suggest that the growth and survival of this tumor is highly dependent upon COX2 (cyclo-oxygenase-2) pathway signaling. Drugs that block this pathway, however, have affects on parallel pathways that appear in some cases to promote tumor survival. Our laboratory investigations seek to understand these mechanisms and thereby, design better drugs or combination chemotherapy strategies which will be effective in treating this cancer. The findings in these studies undoubtedly will form the basis for the design of clinical trials in humans.
Our parallel objectives are to help link the experience and clinical expertise of surgeons with basic scientists and their tools to advance molecular medicine . In addition to research and bridging clinicians with basic scientists, we are also equally committed to teaching and mentoring clinician scientists. It is by inspiring young minds that we hope to push medicine to the next level.

■Dr. Diane M. Simeone
Dr. Diane M. Simeone is an Associate Professor of Surgery in the Section of General Surgery, Division of Gastrointestinal Surgery and Associate Professor of Molecular and Integrative Physiology. Dr. Simeone received her bachelor's degree from Brown University in Providence, Rhode Island and a medical degree from Duke University Medical School in Durham, North Carolina. She completed her General Surgery residency training in 1995 at the University of Michigan Medical Center. She joined the faculty at the University of Michigan Medical Center in 1995. Dr. Simeone's clinical interests are in the area of gastrointestinal oncology. She has a special interest in the surgical treatment of pancreatic adenocarcinoma, and is the Surgical Director of the Multidisciplinary Pancreatic Cancer Clinic. Dr. Simeone is the principal director of a research laboratory that is funded by the National Institutes of Health. Her basic science laboratory investigates mechanisms of pancreatic growth regulation and molecular events important in the development and progression of pancreatic adenocarcinoma. She is also an associate member of the Early Detection Research Network (EDRN), an NCI-funded initiative to identify and validate early detection biomarkers for the diagnosis of pancreatic cancer.

■Dr. Thea Tlsty
Dr. Thea Tlsty, Professor, Pathology, UCSF, Member, UCSF Biomedical Sciences Program (BMS) and Herbert Boyer Program in Biological Sciences (PIBS), Member and Co-Leader, Cell Cycling and Signaling Program, UCSF Comprehensive Cancer Center

Genomic integrity is maintained by a network of cellular activities that assesses the status of the genome at a given point in time and provides signals to proceed with or halt cell cycle progression. Mutations in any part of these cellular pathways can have the ultimate effect of disrupting chromosomal integrity. We have used viral proteins involved in malignant transformation as well as cells from patients predisposed to cancer, to investigate cellular pathways that may be perturbed during loss of genomic stability. Recent studies have identified cellular proteins which are targets for the viral oncoproteins, stressing the importance of these cellular proteins in controlling neoplasia. Among the targets of the viral oncoproteins are the products of the p53 and retinoblastoma (Rb) tumor suppressor genes. We demonstrate that the expression of human papillomavirus type 16 E6 and E7 oncoproteins in normal, mortal cells disrupts the integration of signals that maintain genomic integrity. E6-expressing cells, in which cellular p53 protein is bound and degraded exhibited alterations in cell cycle control and displayed the ability to amplify the endogenous CAD gene when placed in the drug PALA. Expression of E7, which complexes with a variety of cellular proteins, including Rb, resulted in a p53-independent alteration in cell cycle control, massive cell death and polyploidy upon PALA treatment. These results demonstrate that the viral proteins disrupt cellular processes that safeguard the genome and growth of normal cells. More recent studies using cells from patients predisposed to cancer have focused on the enzymatic mechanisms that underlie the processes described above. The identification of these activities in human cells will be presented.

■Dr. Jennifer F Tseng

Clinical Interest
Gastrointestinal Surgery
Pancreatic Surgery
Hepatobiliary Surgery

Practice Location
Worcestter, MA

Primary Hospital
UMass Memorial Medical Center

Board Certification
American Board of Surgery

UMass Medical School
Appointment Assistant Professor

Medical Degree
University of California, San Francisco (1995)

Massachusetts General Hospital

MD Anderson Cancer Center
Children’s Hospital Boston

■Dr. Roger Y. Tsien
Dr Tsien is a Professor of Pharmacology at the University of California, San Diego, School of Medicine and Professor of Chemistry and Biochemistry at the University of California, San Diego.
Roger Tsien’s fascination with colors has revolutionized the fields of cell biology and neurobiology by allowing scientists to peer inside living cells and watch the behavior of molecules in real time. He is renowned for developing colorful dyes to track the movement of calcium within cells and has genetically modified molecules that make jellyfish and corals glow, creating fluorescent colors in a dazzling variety of hues. These multicolored fluorescent proteins have been used by scientists worldwide to track where and when certain genes are expressed in cells or in whole organisms. Now, Tsien is building on his fluorescent protein work to develop a novel way to image and possibly even deliver specially targeted drugs to cancer tumors.
Tsien has always been drawn to pretty colors. “Your science should ideally feed the deeper parts of your personality, to provide some intrinsic pleasure to tie you over the inevitable periods of discouragement,” he says. Tsien grew up among a number of engineers in his extended family, and even from a young age he seemed destined for a career in science. Childhood asthma often kept Tsien indoors, where he spent hours conducting chemistry experiments in his basement laboratory and was first exposed to the chemistry of pretty colors. At 16, he won top prize in the nationwide Westinghouse Talent Search. He later attended Harvard College on a National Merit Scholarship, graduating at age 20 with a degree in chemistry and physics.
As a graduate student at the University of Cambridge, Tsien worked to develop a better dye to track inside cells the levels of calcium, which plays a critical role in numerous physiological processes, including the regulation of nerve impulses, muscle contraction, and fertilization. At that time, measuring intracellular calcium was a laborious process and typically involved injecting a calcium-binding protein through the cell membrane, a technique that often damaged the very cells being studied. Using techniques of chemistry, Tsien developed organic dyes that twist when they bind calcium, dramatically changing the dyes’ fluorescence, and he found a way to masquerade the dyes so they could pass through the cell membrane without having to be injected.
In the early 1990s, Tsien borrowed from jellyfish a molecule that glows, green fluorescent protein, and reengineered it to emit colors ranging from blue to yellow. The fluorescent proteins can be tagged to certain genes or specific proteins of interest. Using a light microscope, scientists can easily determine by their glow when and where the genes are activated or the proteins are expressed. Over the years, Tsien has expanded the color palette of fluorescent proteins to include oranges, reds, and purples. He has also developed a way to monitor the interactions of two proteins, each tagged with different hues of fluorescent proteins. “As a whole, fluorescent proteins have had a huge impact on many areas of biological sciences because they gave [scientists] a direct link from genes and DNA to something you can see inside a cell or inside any organism,” Tsien says, while also acknowledging that other scientists initially discovered and cloned fluorescent proteins.
Tsien recently has set his sights on the imaging and treatment of cancer. He and his colleagues have built U-shaped peptide molecules to carry a payload—an imaging molecule or chemotherapy drug. The peptides are substrates for certain proteases, protein-cleaving enzymes that are exuded from tumor cells but rarely appear on normal cells. When the protease cleaves the bottom of the U, the two arms of the U are separated, unleashing one arm to drag the payload portion of the peptide into a neighboring cancer cell. “I’ve always wanted to do something clinically relevant in my career, if possible, and cancer is the ultimate challenge,” Tsien says.

■Dr. David Tuves
Dr. David Tuveson’s area of interest is tumour modelling & experimental medicine in pancreatic cancer. Dr. Tuveson’s Research Goals: Pancreatic cancer and melanoma are deadly malignancies when detected at late stages. Our laboratory investigates both of these cancers by producing models in Mus musculus that mimic the human diseases closely, and participating in clinical trials with experimental therapeutics. The goals of the laboratory are to identify the essential components of malignant transformation of pancreatic cells and melanocytes in vivo, and to translate this knowledge into effective tumour detection and treatment strategies.

■Dr. Inder M. Verma

Dr. Inder M. Verma, a professor in the Laboratory of Genetics and American Cancer Society Professor of Molecular Biology, is one of the world’s leading authorities on the development of viruses for gene therapy vectors. Dr. Verma uses genetically engineered viruses to insert new genes into cells that can then be returned to the body, where they produce the essential protein whose absence causes disease. Dr. Verma and his fellow Salk Institute colleagues developed a gene therapy vector, based on a stripped-down version of HIV, that can deliver genes to non-dividing cells, which constitute the majority of the cells in our bodies. Dr Verma’s group is also studying two genes implicated in familial breast cancer, BRCA1 and BRCA2, and recently demonstrated that their action is linked to the cell’s division cycle and that BRCA1 regulates gene activity. Dr Verma‘s group also studies the molecular mechanisms of NF-kB a family of proteins involved in immunity and cancer. Dr Verma holds an M.Sc in Biochemistry Lucknow University, India a Ph.D in Biochemistry from the Weizmann Institute of Science, Israel and Postdoctoral fellow in Biology at the Massachusetts Institute of Technology. with David Baltimore.
Dr Verma’s awards and honors include the NIH Outstanding Investigator Award 1988,The Third World Academy of Sciences, National Academy of Sciences( US), March of Dimes Birth Defects Foundation Franklin D.Roosevelt Investigator 1999, Institute of Medicine, Academy Of American Art And Sciences, Foreign associate of EMBO and Indian Academy Of Sciences.
From 2000-2001 Dr Verma served as President of the American Society for Gene Therapy.

■Dr. Selwyn M. Vickers
Jay Phillips Professor and Chairman
Department of Surgery
Clinical Interests
Pancreatic cancer
Bile duct cancer
Gastrointestinal cancer

Gene therapy as an application in the treatment of pancreatobiliary tumors.
The role of growth factors and receptors (FGF, EGFR) in the oncogenesis of pancreatic cancer.
The implications of FAS expressions and Tamoxifen in the growth and treatment of cholangiocarcinoma.
Assessment of clinical outcomes in the surgical treatment of pancreatobiliary tumors.
The role of death receptors in the treatment of pancreatic cancer.

■Dr. Geoffrey M. Wahl
Dr. Geoffrey M. Wahl is a Professor in the Gene Expression Laboratory at the Salk Institute. His research concerns the cellular and genetic bases of the origin and progression of cancer and the development by tumors of resistance to drugs.
Dr. Wahl graduated Magna Cum Laude from the University of California, Los Angeles in 1970 with a B.A. in Bacteriology. In 1975 he received a PhD in Biological Chemistry from Harvard University, where he studied with Dr. Mario Capecchi. He was a Research Assistant Professor at the University of Utah from 1975 to 1976 and was a postdoctoral fellow at Stanford University from 1976 to 1979 in the laboratory of Dr. George Stark. He then joined The Salk Institute as an Assistant Professor in the Molecular Biology and Virology Laboratory. Dr. Wahl received his present appointment as Professor in the Gene Expression Laboratory in 1989. He is also an Adjunct Professor at the University of California, San Diego.
Dr. Wahl’s overarching interests concern the mechanisms that initiate tumor formation, and that mediate progression of cells to malignancy. His early research at the Salk Institute involved analyses of the molecular mechanisms of gene amplification, a form of genetic instability that is unique to cancer cells. His laboratory provided the first direct evidence that the process is initiated by DNA breakage that can be stimulated by inappropriate entry of cells into DNA replication. His work then broadened to elucidate the molecular mechanisms that prevent unscheduled cell cycle progression in normal cells as well as to identify and characterize the DNA replication origins at which replication initiates. This work led to the finding that the p53 tumor suppressor plays a key role in linking cell cycle progression to genetic instability. His group showed that p53 is activated under growth challenging conditions to induce either senescence or cell death to prevent variants with genetic instability from arising. These studies led to the concept that p53 is "The Guardian of the Genome". His group also developed molecular genetic strategies to identify, isolate, and characterize mammalian replication origins.
Dr. Wahl has published more than 130 articles, reviews and book chapters related to genetic instability, p53 functions and control, and the control of DNA replication. He has contributed to the development of numerous technologies in wide use in molecular and cellular biology, is the author of a citation classic concerning methods of DNA detection, and is the holder of a number of patents. He serves as a reviewer for major biomedical journals, is on several editorial Boards, has been the co-chair and Program Chair of three Annual meetings of the American Association for Cancer Research (AACR), and was elected as President of AACR for 2006-2007.

■Dr. Bonner-Weir
Dr. Bonner-Weir is Senior Investigator in the Section on Islet Transplantation and Cell Biology at Joslin and Associate Professor of Medicine at Harvard Medical School. Dr. Bonner-Weir received her doctorate in biology at Case Western Reserve University and then completed postdoctoral training in islet morphology at Harvard Medical School. She serves or has served on the editorial boards of the American Journal of Physiology, Endocrinology and Diabetes, and is a member of the Juvenile Diabetes Research Foundation Scientific Review Committee.

Senior Investigator Dr. Bonner-Weir and her colleagues believe that a better understanding of the regulation of pancreatic growth and differentiation may lead to new therapies, including genetic engineering of new beta cells and amplification of beta cells from the pancreas (either human or animal) to be used for transplantation.
Her research has focused on the endocrine pancreas (the islets of Langerhans) in three areas: 1) the architecture of the islet and its implications for function; 2) the in vivo regulation of beta-cell mass; and 3) the factors involved in islet growth and differentiation.

With a series of rodent models they have provided compelling evidence that adult pancreatic beta-cell mass increases in response to a metabolic need and have been examining the mechanisms of this postnatal pancreatic growth. In the adult rat after partial pancreatectomy, massive regeneration occurs with both enhanced replication of preexisting beta cells and ductal expansion and subsequent differentiation into endocrine, exocrine or mature duct cells. Their hypothesis has been that in the adult pancreas duct cells act as a “facultative stem cells”, such that with replication the mature duct cell regresses to a less differentiated cell (perhaps equivalent to a embryonic pancreatic duct cell) and regains its potential to differentiate into islet, acinar or mature duct cell, and that this phenotypic differentiation is directed by external signals or morphogens. Using molecular biological and immunochemical techniques we are defining the cells that are involved and the factors that are carefully orchestrated in vivo to stimulate the growth and differentiation of the beta-cells. Additionally they have been successful in vitro cultivation of human islets from pancreatic ductal cells and are characterizing the cells that give rise to the new islets.

■Dr. Timothy J. Yeatman

Dr. Yeatman is the Associate Center Director for Clinical Investigations, H. Lee Moffitt Cancer Center & Research Institute. Dr. Yeatman has focused his research on the management of gastrointestinal malignancies with a special research emphasis on using genome scale microarrays to identify the molecular signatures of cancer that provide diagnosis, prognosis and response to therapy. Dr. Yeatman recently compared microarray data of 540 human tumors of 21 different tumor types with the diagnoses obtained from tumor biopsies. He found that microarray was 88 percent accurate in predicting all tumor types. The results of his investigation, the first such work to be reported in this depth, appeared in the January 2004 issue of the American Journal of Pathology. In addition, he and his colleagues have detected 340 new tumor markers and more than 100 tumor progression markers whose expression correlated with progressing tumor stage. Some of these markers may be useful in the clinical management of colon cancer patients because of their capacity to detect and predict the stage of cancer.


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