2017 Ruth Leff Siegel Award Winners
Dr. George Miller from New York University School of Medicine is the recipient of the $50,000 Ruth Leff Siegel Award. He was recognized for 2 recent seminal papers which elucidate our understanding of immune-suppression in pancreatic carcinoma and can have impact on the potential immunotherapy of this disease. His paper entitled “γδ T Cells Support Pancreatic Oncogenesis by Restraining αβ T Cell Activation” (Cell, 2016) identified a distinct γδT cell population, which constituted up to 70% of all tumor-infiltrating T cells in human pancreatic cancer. His research highlighted that specific γδT cell populations are key suppressors of effector T cell activation in tumors via reciprocal cross-talk. This study lays the framework for targeting γδT cells as a novel immunotherapy strategy for pancreatic cancer. His other paper entitled “The Necrosome Promotes Pancreas Oncogenesis via CXCL1 and Mincle Induced Immune Suppression” (Nature, 2016) investigated the significance of necroptosis, or programmed necrosis, in pancreas cancer. Dr. Miller’s group showed that pancreatic cancer cells – which were widely believed to die via apoptosis – also die via necroptosis which is dependent on RIP1 and RIP3 co-association. They showed that chemotherapy can further induce cancer cell death by necroptosis. However, despite its primary effect in facilitating cancer cell death, Dr. Miller discovered that necroptosis paradoxically promotes pancreatic oncogenesis via its secondary effects in driving immune-suppressive inflammation. His mechanistic work elucidated parallel networks of necroptosis-induced CXCL1 and Mincle signaling which promote myeloid cell-entrained suppression of T cell immunity which enabled pancreatic cancer progression. The scientific import of this discovery is high as the necrosome and Mincle had not previously been linked to oncogenesis. Moreover, this work identifies multiple potential targets for immunotherapy (RIP1, RIP3, CXCL1, Mincle) which can be tested in the clinic.
Dr. Miller is Associate Professor at NYU School of Medicine where he holds the H. Leon Pachter Chair in Surgery. He is Vice-Chairman for Research in the Surgery Department, leader of NYU’s Tumor Immunology Program, and Director of its T32 training program in GI Oncology. Dr. Miller is a physician-scientist in the real sense. From a clinical standpoint, he performs complex operations in patients with liver and pancreatic cancer. Nevertheless, 80% of his time is dedicated to basic and translational cancer immunology research. His lab has been a leader in illuminating immune-regulatory networks in the pancreatic cancer tumor microenvironment. Dr. Miller is PI on 4 current R01 grants, he has received a number of foundation awards, and he has trained a cadre of physician-investigators, all of whom have received prestigious training grants and are embarking on academic careers. A number of his findings in the lab are being translated into investigator-initiated clinical trials. He also recently founded a start-up company NYBO Therapeutics which is developing new immunotherapy drugs based on work in his lab. Dr. Miller has chaired federal grant study sections and is Editor-in-Chief of Oncogene.
The recipient of the $25,000 award is Dr. Susan Bates for her work as editor in chief of the dedicated pancreas Clinical Cancer Research journal titled “Pancreatic Cancer: Challenge and Inspiration” published in April 2017.
Dr. Bates received her M.D. degree from the University of Arkansas School of Medicine. She completed her clinical training in internal medicine at Georgetown University in Washington, D.C., and in medical oncology at the National Cancer Institute (NCI) in Bethesda, MD. Dr. Bates was a Lead Clinical Investigator and Head of the Molecular Therapeutics Section in the Developmental Therapeutics Branch of the Center for Cancer Research before moving to Columbia University in August 2015.
Dr. Bates' current interests are both laboratory and clinical in nature. Her laboratory efforts include laboratory and translational studies on drug resistance in T-cell lymphomas and advanced solid tumors including breast, pancreatic, neuroendocrine, renal and lung cancers. Her work is dedicated to new drug development, and finding antineoplastic agents that, alone or in combination with other anticancer agents, improve the options available for difficult to treat cancers. Emanating from the clinical and translational development of romidepsin, a histone deacetylase (HDAC) inhibitor, a current focus is on epigenetic therapies, and the development of combination therapies to use with HDAC inhibitors in refractory advanced cancers, including solid tumors. She also has a special interest in drug delivery and drug distribution and the role of the blood brain barrier in creating a sanctuary site for cancers that metastasize to the brain. Clinically, her goal has always been to translate ideas from the laboratory to clinical trials, an effort that has proven very successful. Clinically she seeks to develop combination therapies with histone deacetylase inhibitors for the therapy of solid tumors; and to develop therapies to treat central nervous system metastases, a complication of cancer that is becoming a greater problem as patients live longer with cancer.
2016 Ruth Leff Siegel Award Winners
On behalf of the Siegel Family and the awards selection committee, it is our pleasure to announce the 2016 winners of the Ruth Leff Siegel Award for Excellence in Pancreatic Cancer Research.
Dr. Raghu Kalluri of the University of Texas MD Anderson Cancer Center is the recipient of the $50,000 award. His laboratory is broadly interested in the study of cell and tissue microenvironment and its impact on tissue injury/regeneration and cancer. Recent work from Dr. Kalluri’s group unraveled new patho-mechanisms of pancreatic cancer and offered insights into novel strategies for diagnosis and treatment of pancreatic cancer. His seminal paper was titled “Depletion of Carcinoma-Associated Fibroblasts and Fibrosis Induces Immunosuppression and Accelerates Pancreas Cancer with Diminished Survival”.
Dr. Kalluri is the Chairman and Professor of the Department of Cancer Biology and the Director of the Metastasis Research Center at the University of Texas MD Anderson Cancer Center. Prior to this, he was Chief of the Division of Matrix Biology and a Professor of Medicine at Harvard Medical School. Dr. Kalluri currently holds the Olla S. Stribling Distinguished Chair for Cancer Research and previously held the Rebecca and Joseph Brown Endowed Chair at MD Anderson Cancer Center. In 2015 Dr. Kalluri received the Jacob Henle Medal from the Georg-August University in Germany to honor his contribution to medical research. He serves on science and health advisory panels in the USA and European Union and on the editorial boards of several academic journals representing biology and medicine.
The recipients of the $25,000 are Dr. Timothy C. Wang and Professor Jeanine Genkinger from Columbia University Medical Center. Dr. Wang is being recognized for his findings on Doublecortin-like kinase-1 (Dclk1), a molecular protein, as a marker of quiescent pancreatic progenitor cells that are candidates for the origin of pancreatic cancer, in his paper titled, “Dclk1 Defines Quiescent Pancreatic Progenitors that Promote Injury Induced Regeneration and Tumorigenesis”.
Professor Genkinger is being recognized for her studies on the relationships between central adiposity, a high BMI during early adulthood, and weight gain after early adulthood, in regards to pancreatic cancer risk. Her paper, “Central Adiposity, Obesity During Early Adulthood, and Pancreatic Cancer Mortality in a Pooled Analysis of Cohort Studies” found an association between pancreatic cancer mortality and central obesity, independent of BMI.
Dr. Wang is a Silberberg Professor of Medicine, Chief of the Digestive & Liver Diseases at Columbia University Medical Center, and Director of the GI Cancer Program at CUMC. He received his BA from Williams College and his MD from the Columbia College of Physicians & Surgeons. He has led an independent research lab for over twenty-five years focused on the relationship between inflammation, stem cells and cancer, and the molecular mechanisms of gastrointestinal carcinogenesis. Author of over 250 publications, he has headed up numerous multidisciplinary research programs, including the CUMC NCI U54 Tumor Microenvironment (TMEN) program, the CUMC Barrett’s Esophageal Translational Research Network (BETRNet) program and the Intestinal Stem Cell Consortium (ISCC) at Columbia. He is a recipient of the Merit Award (R37) from NIDDK and the Outstanding Investigator Award (R35 OIA) from the NCI, and the Arthur and Irene Fishberg Prize for outstanding research from CUMC. He is currently President of the American Gastroenterology Association (AGA) Institute.
Professor Genkinger is a cancer epidemiologist who has been driven to understand how modifiable factors, molecular pathways and related biomarkers may impact cancer risk and progression, particularly for pancreatic cancer, a rare but highly fatal cancer. Prevention through determining modifiable risk factors and improved early detection through identifying markers of risk and molecular pathways offer the most promising approaches to reducing morbidity and mortality of these diseases. Her area of methodological specialty is in nutritional epidemiology, longitudinal design and complex pooled and meta-analytic techniques. Dr. Genkinger has conducted her research in large scale international consortia, namely the Pooling Project of Prospective Studies of Diet and Cancer and the NCI Cohort Consortium, and has conducted research in numerous cohort studies, such as the Breast Cancer Family Registry.
2015 Ruth Leff Siegel Award Winners
On behalf of the Siegel Family and the awards selection committee, it is our pleasure to announce the 2015 winners of the Ruth Leff Siegel Award for Excellence in Pancreatic Cancer Research.
The external $50,000 award went to Dr. Steven Leach of Memorial Sloan Kettering Cancer Center, whose animal studies have led to important new understandings of the mechanisms by which pancreatic cancer develops. This investigation has identified a new therapeutic target for chemoprevention and treatment of pancreatic cancer. His seminal paper was titled Oncogenic Kras activates a hematopoietic-to-epithelial IL-17 signaling axis in preinvasive pancreatic neoplasia.
Dr. Leach is the David M. Rubenstein Chair and Director of Memorial Sloan Kettering’s new Rubenstein Center for Pancreatic Cancer Research. He is also an Attending Physician at Memorial Sloan Kettering, Professor of Surgery at Weill-Cornell Medical College and a Member of the MSKCC Human Oncology Pathogenesis Program. Prior to this he was Professor of Surgery, Oncology and Cell Biology, and the Paul K. Neumann Professor in Pancreatic Cancer at Johns Hopkins.
Dr. Leach’s lab has a long track record of research productivity in the field of pancreatic cancer biology, and is known for establishing important links between pancreatic development and pancreatic cancer. These include the discovery of abnormal Notch pathway activation as an important driver of pancreatic tumorigenesis, development of the first zebrafish model of pancreatic cancer, identification of adult acinar cells as effective cells of origin for the initiation of pancreatic “ductal” neoplasia, and the recent discovery of a new stem cell associated with the earliest pre-invasive stages of the disease. Together with their extensive additional studies of pancreatic development and pancreatic epithelial plasticity, work from Dr. Leach’s group has generated important new insights regarding early events in human pancreatic cancer.
Dr. Leach also has extensive administrative experience, including the management of large multi-investigator and multi-institutional research initiatives. He previously served as both Chief of the Division of Surgical Oncology and Vice Chair for Academic Affairs in the Department of Surgery at Johns Hopkins, and he also serves on the Princeton University Board of Trustees.
The internal award of $25,000 went to Dr. Kenneth Olive of the Herbert Irving Comprehensive Cancer Center, for his findings on pancreatic stroma (the “filler cells” that surround pancreatic tumor cells). His paper, Stromal Elements Act to Restrain, Rather Than Support, Pancreatic Ductal Adenocarcinoma, explains how certain stroma cells may actually help restrain pancreatic tumors, and it helped explain the recent failures in human trials of Smoothened inhibitors.
Dr. Olive began his doctoral studies in 1998 in the laboratory of Prof. Tyler Jacks at the MIT Center for Cancer Research, investigating the function of cancer-associated mutations in a tumor suppressor gene called p53. While at MIT, he also helped develop a new model of advanced lung adenocarcinoma. After graduating in 2005, Dr. Olive began a fellowship in the laboratory of Prof. David Tuveson at the University of Pennsylvania, later moving with the lab to the University of Cambridge in England. There he built a translational research facility for studying novel anticancer therapeutics in genetically engineered mouse models of pancreatic cancer. Using this infrastructure, he determined that stroma cells limit the delivery of drugs to pancreatic tumors, providing an explanation for why pancreatic tumors are resistant to so many different drugs. Dr. Olive joined the faculty of the Columbia University Herbert Irving Comprehensive Cancer Center in January of 2010, where he is continuing his investigations into the response of pancreatic tumors to therapeutic interventions. He is also the founding director of the Small Animal Imaging Shared Resource (SAISR) within the Herbert Irving Comprehensive Cancer Center.
2014 Ruth Leff Siegel Award Winners
On behalf of the Siegel Family and the awards selection committee, it is our pleasure to announce the 2014 winners of the Ruth Leff Siegel Award for Excellence in Pancreatic Cancer Research.
Dr. Alec Kimmelman of the Dana Farber Cancer Institute (Harvard Medical School) and Dr. Gloria Su of the Herbert Irving Comprehensive Cancer Center (Columbia University Medical Center) were selected to receive this year's award. A ceremony to celebrate both winners will be held on September 18, 2014 with the Siegel family and the award committee.
Dr. Kimmelman will provide a keynote address at the Herbert Irving Comprehensive Cancer Center 2014 Annual Retreat on Monday, October 20, 2014.
Dr. Kimmelman's work has focused on the unique metabolism of pancreatic cancer cells; essentially he has clarified how pancreatic cancer cells burn fuel to survive. He has identified that these cells are dependent on a process of metabolic recycling called autophagy and that they are uniquely dependent on the amino acid glutamine. His most recent observation is that these changes in cellular metabolism are driven by oncogenic Kras, the most commonly observed genetic alteration in pancreatic cancer. The concepts Dr. Kimmelman has developed are immediately translatable and are being tested in two ongoing clinical trials.
The theme of Dr. Su's work in pancreatic cancer has been in elucidating the genetic drivers of the disease. She has developed mouse models that spontaneously develop both the typical pattern of pancreatic cancer preceded by PanIn changes as well as the less common form that follows the development of intraductal papillary mucinous neoplasia (IPMN). In her critical paper published in the November 2013 issue of Clinical Cancer Research, she identified the importance of the loss of PTEN in the aggressiveness of human IPMN. Deepening our understanding of the genetic events that drive IPMN toward cancer will allow for better selection of patients for prophylactic pancreatectomy to prevent pancreatic cancer.
2013 Ruth Leff Siegel Award Winners
Dr. Ralph H. Hruban was awarded the external prize for his numerous contributions to the genetic and pathologic characterizations of pancreatic cancer. His 2012 paper entitled, "Pancreatic Cancer Genomes Reveal Aberrations in Axon Guidance Pathways Gene," was his most recent contribution which put him over the top for our selection committee. The impact of the huge number of scientists he has inspired to commit their careers to pancreatic cancer cannot be measured but is perhaps his greatest contribution to the field.
Dr. Robert Lance Fine was awarded the internal Columbia University prize for his development of GTX, presented at the American Society of Clinical Oncology (ASCO) 2013 Gastrointestinal (GI) Cancer Symposium. We honor him for his ongoing commitment to advancing pancreatic cancer therapies through basic science and translational research.
Our awardees were chosen from among many highly respected nominees for their work in the field of pancreatic cancer. We would like to commend all the nominees on their contributions and efforts and thank the nominators for their time and effort as well.
Your continued commitment to finding a cure is necessary for the inspiration of future generations. We encourage you to apply for the 2015 award. Information and guidelines will be posted on our website — www.pancreascenter.com.