- About CURE
Evolution of the Research Activities at CURE and creation of the CURE: DDRCC.
CURE initially established its reputation for its work in peptic ulcer disease and the acronym CURE was derived from Center for Ulcer Research and Education. It began in 1974 before effective antisecretory therapy had been established as a modality for treatment of peptic ulcer disease. The objectives of the CURE investigators were to find the causes and best methods for prevention, diagnosis, and treatment of peptic ulcer and related mucosal diseases and to disseminate this information to health professionals and to the public. Great progress has been made in achieving these goals through the efforts of CURE. The development of H2 antagonists fundamentally changed the concepts surrounding the stimulation of parietal cell acid secretion. In the first decade of CURE’s existence, much of the research involved dissection of the pathways implicated in stimulation of the parietal cell. After establishing the mechanism of acid secretion as being a function of gastric parietal cell H,K-ATPase, a new era in ulcer therapy began with the introduction of the substituted benzimidazoles.
A major emphasis of research in the second decade of CURE was on elucidating the mechanisms by which the H,K-ATPase catalyzes the exchange of intracellular H+ for extracellular K+ at the expense of ATP in parietal cells and in development of drugs that inhibit the activity of this enzyme. More recently, it has been demonstrated that gastric and duodenal ulcer diseases are associated with infection by H. pylori. In the mid-1990s, work at CURE defined a major aspect of the gastric biology of the organism in identifying mechanisms that allow it to survive in the acid environment of the stomach. This concept has brought mucosal cell biology into the forefront of research at CURE. The interests and activities of CURE have evolved along with science in this area and now include several facets of gastrointestinal regulatory physiology and cell biology.
The original Director and founder of CURE was Morton I. Grossman, a pioneer of modern gastrointestinal endocrine physiology. Dr. Grossman was one of the first scientists appointed to the newly created Senior Medical Investigator program at the Veterans Administration. He was also Professor of Medicine and Physiology at the UCLA School of Medicine. Dr. Grossman was later joined by Charles Code, a renowned gastrointestinal physiologist, as an Associate Director. After Dr. Grossman’s death in 1981 and Dr. Code’s retirement in 1982, a national search led to the recruitment of George Sachs as Director in 1982. Dr. Sachs also held the position of VA Senior Medical Investigator. In 1987, John H. Walsh, previously Deputy Director, was named Director of CURE, and Dr. Sachs became Co-Director. At that time, Drs. Yvette Taché and Dennis Jensen were appointed Associate Directors.
Regulation of gastrointestinal function by hormones, especially gastrin, was another of the earliest interests of CURE and was the special province of its founder, Dr. Grossman. Members of CURE were able to utilize in vivo immunoneutralization to prove that circulating gastrin was an essential regulator of food-stimulated gastric acid secretion. The major target for circulating gastrin was found to be the gastric enterochromaffin-like (ECL) cell, from which gastrin stimulates histamine release that, in turn, activates parietal cell histamine-2 receptors to stimulate acid secretion through a paracrine mechanism. George Sachs made a major advance in the study of ECL cell function by developing a purified preparation of these cells that demonstrated histamine secretion and proliferation in response to physiological concentrations of gastrin. Subsequent collaborations between George Sachs and the late John Walsh developed methods to study intracellular Ca2+ responses to various peptides in G cells and D cells and to define inhibitory receptors on isolated ECL cells that oppose the stimulatory actions of gastrin.
Over the years, CURE has grown and evolved into a broadly based gastrointestinal research organization with multiple affiliations with the VA, UCLA, and leading national and international research universities. The establishment of the NIDDK-supported CURE: Digestive Disease Research Core Center (CURE: DDRCC) in 1989 greatly facilitated the research, recruitment, training, and continued development of young investigators in the fields of gastroenterology and related sciences at UCLA and the Veterans Administration Greater Los Angeles Healthcare System (VAGLAHS). The visibility of the Center has enhanced the attractiveness of digestive diseases-related research to scientists and physician scientists who are committed to research careers (See next section: Biomedical Research Base). Since its inception in 1989 and until 2000, the CURE: DDRCC was directed by Dr. John H. Walsh. The major importance of this continuously funded Center grant to the host institutions is best indicated by the operational organization created when the CURE: DDRCC was first funded in 1989. The Principal Investigator of the CURE: DDRCC was also the Director of CURE (i.e., the overarching organization funded by many other granting agencies, both public and private) and Chief of Research in the UCLA Division of Digestive Diseases.
In 1998, Drs. Emeran Mayer, J. Enrique Rozengurt and Ernest Wright were added to the team of Associate Directors to reflect the new directions in enteric neuroscience, signal transduction and molecular transport being incorporated into the CURE: DDRCC biomedical research base. CURE continued to provide an infrastructure to support basic, translational and clinical research and to facilitate interdisciplinary research and training activities in digestive diseases, mainly involving the David Geffen School of Medicine at UCLA and the VAGLAHS. The interests and activities of CURE investigators continue to evolve and diversify in response to scientific advances and included gastrointestinal pathophysiology, enteric neuroscience and cell biology.
In June 2000, Dr. John H. Walsh passed away suddenly. A national search was conducted by a UCLA and VAGLAHS Search Committee to identify outstanding candidates to succeed Dr. Walsh as Director of CURE, the overarching organization. The Search Committee recommended that Dr. J. Enrique Rozengurt should be appointed the new Director of CURE and significant new institutional resources came with this appointment. Accordingly, the leadership of the David Geffen School of Medicine at UCLA and that of the VAGLAHS appointed Dr. Rozengurt CURE Director in June 2002 and subsequently, he became PI and Director of the NIDDK-supported CURE: DDRCC after approval by the NIDDK Program Director. Dr. Emeran Mayer was named Co-Director of the Center and Dr. Catia Sternini Associate Director, with responsibility for the Pilot and Feasibility Study and Named New Investigator Program.
The appointment of Dr. Rozengurt recognized the overarching relevance of cell signaling for understanding basic biologic functions, functional disorders and diseases of the digestive system, including digestive cancers. The clinical and translational scientific interests of other members of the current CURE: DDRCC leadership, including Drs. Emeran Mayer, Dennis Jensen, Steve Pandol, Charalabos Pothoulakis and Catia Sternini complement those of Dr. Rozengurt. While retaining traditional areas, the programs supported by the CURE: DDRCC expanded and broadened, shifting toward understanding the molecular cellular and physiological mechanisms underlying normal and abnormal processes of the digestive system. In view of its national and international recognition, the acronym CURE, initially derived from Center for Ulcer Research and Education, has been retained but over the years it could more precisely denote Comprehensive Umbrella of Research and Education in Digestive Diseases. The impact of CURE since its inception in 1974 and of the CURE: DDRCC since 1989 on the field of digestive diseases research is especially apparent in its accomplishments in peptic ulcer disease research, in gastric regulatory physiology and more recently in elucidating brain-gut interactions and molecular mechanisms of action of gastrointestinal peptides as well as in the scientific training and education of many scientists and physician scientists who later became leaders in the field.
Among the trainees and junior faculty who have obtained prominent positions in the United States and abroad are: Haile Debas, Maurice Galante Distinguished Professor of Surgery and Dean Emeritus of the UCSF School of Medicine; Tadataka Yamada, former Chair of Medicine, University of Michigan, former President of SmithKline Beecham Healthcare Services and currently president of the Global Health Program of the Bill and Melinda Gates Foundation; Ian Taylor, former Dean, School of Medicine, Tulane University, AGA President-Elect ; Gordon Kauffman, Professor and Vice Chair of Surgery; Professor of Cellular and Molecular Physiology, Pennsylvania State University; Theodore N Pappas, Chief of General Surgery, Duke University; Charles Brunicardi, former Chief of General Surgery, Baylor College of Medicine; Neil Kaplowicz, Chief of the Division of Gastrointestinal and Liver Diseases, University of Southern California; Irvin Modlin, Director of Gastric Pathobiology, Yale University Medical School; Viktor Eysselein, Chief of Gastroenterology, Harbor-UCLA Medical Center; Nigel Bunnett, former Professor and Vice Chair, Departments of Surgery and Physiology, UCSF; Stanley Ashley, Vice Chairman, Department of Surgery, Brigham and Women’s Hospital; Hal Yee, former Chief of Gastroenterology and Hepatology, San Francisco General Hospital; Maria Abreu, Chief of Gastroenterology, Miami Leonard M. Miller School of Medicine; K. C. Kent Lloyd, Associate Dean for Veterinary Research and Graduate Education Programs in the Dean's Office and Associate Professor of Anatomy in the Department of Anatomy, Physiology & Cell Biology, UC Davis; Juanita Merchant, Professor, Department of Internal Medicine and Professor of Molecular and Integrative Physiology and Director of a program project to study molecular mechanisms responsible for cell growth, differentiation and apoptosis; Helen Raybould, Chair, Department of Anatomy, Physiology and Cell Biology, UC Davis and Fergus Shanahan Professor and Director of University College Cork's Alimentary Pharmabiotic Center, National University of Ireland, Cork.
Many other trainees have full-time faculty positions in the United States and abroad, and many have obtained independent NIH support. Others former trainees, including Jonathan Kaunitz, Emeran Mayer, Joseph Pisegna, Catia Sternini and Yvette Taché have developed careers at UCLA and VAGLAHS. This tradition is continuing, as shown by the number of our more recent trainees and faculty, including Simon Beavan, Lin Chang, Guido Eibl, Samuel French, J. Oscar Hines, Lisa Kilpatrick, Martín Martín, Muriel Larauche, Juan Carlos Marvizon, Million Mulugueta, Osvaldo Rey, Brennan Spiegel, Kirsten Tillisch, and Hong Yang who have secured independent funding from NIH, AGA and/or VA sources, thus launching their own scientific careers. CURE has also played a critical role in the recruitment of outstanding scientists and physician scientists to UCLA and the VAGLAHS, including Drs. George Sachs, Stephen Pandol, J. Enrique Rozengurt, Noriyuki Kasahara, Charalabos Pothoulakis. Recently CURE has played an important role in attracting back Charles Brunicardi to UCLA and CURE.