Research Activities
Excellence in biomedical research constitutes the principal emphasis and effort of the Section of Gastroenterology at Boston University School of Medicine, which continues to gain prominence in both basic and clinical research arenas. The research emphasis includes epithelial cell biology, gastrointestinal carcinogenesis, and obesity and other metabolic disorders. With regard to clinically oriented research, Dr. Paul Schroy has attained significant notoriety and prominence on the national and international levels as a leading investigator in developing colorectal cancer screening strategies. He is also investigating the use of other modalities for the detection of colorectal cancer, including virtual colonoscopy and stool-based DNA testing modalities. Dr. Brian Jacobson successfully procured a KO8 grant from the NIH to investigate the natural history of Barrett’s esophagus in women in the Nurse’s Health Study. Dr. Jacobson, along with Dr. Schroy have thus formed the nucleus for the future development of health services research in the Section of Gastroenterology.
In addition to Drs. Schroy and Jacobson, Dr. David Nunes has continued his active collaboration with the Section of Infectious Diseases at Boston University as a Co-Investigator of an NIH grant that evaluates interactions in individuals co-infected with hepatitis C and HIV. He has also continued to obtain funding from industry to evaluate various treatment modalities for hepatitis C and other hepatitidies. Along with Dr. Robert Lowe, these studies constitute a very important sector of the clinical research being performed in the Section of Gastroenterology. Dr. Albena Halpert is involved in the examination of various strategies for the management of functional bowel disorders.
Dr. Marcos Pedrosa, Director of Endoscopy at the Boston VA Medical Center, is continuing his studies investigating surveillance strategies, as well as treatment of, Barrett’s esophagus. Like Drs. Nunes and Lowe, he is engaged in hepatitis C protocols, utilizing various agents to treat this very common disorder. He was also actively involved in studies that include other investigators throughout the United States in the use of photodynamic therapy (PDT) for the ablation of high-grade dysplasia in Barrett’s esophagus. Finally, he has been an active participant in VA cooperative studies evaluating the use of colchicines and other agents in the treatment of alcoholic liver disease. Finally, Dr. Francis Farraye, Director of Clinical Services for the Section, has continued his clinical studies in patients with inflammatory bowel diseases.
With regard to basic biomedical research, two laboratories continue to concentrate their efforts on investigating the roles of various transcription factors and gastrointestinal regulatory peptides in the pathophysiology of colorectal cancer and other gastrointestinal neoplasms. Dr. H. Christian Weber is examining the role of receptors to bombesin-like peptides in the development of gastrointestinal malignancies. In addition to their role in the development of gastrointestinal neoplasia, he has begun to collaborate with members of the Obesity Center at Boston University in determining the role of these peptides in obesity and in appetite suppression. Dr. Wolfe has continued his studies examining the role of the regulatory peptide gastrin in the pathogenesis of both colorectal cancer (CRC) and esophageal adenocarcinoma, and he has expanded investigation to examine the mechanisms by which cyclooxygenase (COX) isoenzymes play a role in the development and natural history of CRC. Along with his two collaborators, he has recently found that suppression of colorectal cancer growth can be best accomplished by the use of a combination of COX inhibitors, rather than suppression of COX-2 only. Their studies will also include investigation aimed at determining the functional significance of gastrin receptors in esophageal adenocarcinoma cell lines of human origin and in Barrett’s metaplasia.
The other NIH-funded area of investigation in Dr. Wolfe’s laboratory is the contribution of gastrointestinal regulatory peptides in the pathogenesis of obesity, and specifically the role of glucose-dependent insulinotropic polypeptide (GIP) on lipid homeostasis and in the development of obesity. He has been utilizing various animal models that simulate the Roux-en-Y gastric bypass procedure and has determined that much of the benefit of this operation is derived from bypassing of the area in which GIP is both synthesized and released in the circulation. He continues to utilize his GIP-specific receptor antagonist that was developed in his laboratory to perform these important physiological studies and collaborates on an ongoing basis with Dr. Barbara Corkey in the Obesity Unit of the Section of Endocrinology. This antagonist is also being evaluated for potential use in the treatment and prevention of obesity type 2 diabetes mellitus. Dr. T. Carlton Moore continues to work with Dr. Wolfe on the development of a bioassay for the measurement of GIP that will enable this laboratory and other investigators to accurately determine the concentration of GIP in plasma and tissue samples in both humans and other animals. Dr. Wolfe also continues his collaboration with Ms. Lisa Jepeal in examining the regulation of the GIP gene and its specific relationship to insulin expression, as well as the ontogeny of GIP-producing cells in the intestine. These studies will form the basis for eventual attempts at gene therapy to direct insulin expression in GIP-producing K-cells of the upper small intestine. Dr. Wolfe has recently begun to collaborate with Dr. Satish Singh in determining the mechanisms by which GIP suppresses glucose absorption in the GI tract. These studies will have important implications with regard to not only the pathogenesis of obesity, but also to potential treatment modalities in the future. In addition to his collaboration with Dr. Wolfe in investigating mechanisms by which GIP affects glucose transport in the small intestine, Dr. Satish Singh continues to investigate the barrier and transport processes that participate in maintaining the intracellular pH of epithelial cells with in the intestine mucosa.
In collaboration with Michael Boylan, Ph.D., Dr. Wolfe has been examining the proposed use of engineered stem cells implanted in the small intestinal mucosa and programmed to synthesize and release therapeutic peptides into the systemic circulation. Once implanted in patients, these stem cells will assume many of the characteristics of neighboring cells of the small intestinal lining in which they now reside. After a sufficient number of cells expressing the therapeutic peptide have been prepared, Dr. Wolfe plans to use minimally invasive endoscopic techniques to implant them into the proximal small intestinal lining. Dr. Wolfe received a prestigious Hartwell Foundation Award to conduct these studies.
Dr. Gwynneth Offner continues her investigation on the role of mucins in the biliary tract, gallbladder, gastrointestinal tract, and the oral cavity. She has continued her collaboration with Dr. Michael O’Brien in studies examining the molecular mechanisms of hepatic fibrosis. Dr. Offner has also continued her active collaborative program with members of the Boston University School of Dentistry to examine the structure and function of human salivary mucins, and they have been performing these studies to determine the mechanisms by which mucins lead to different functions in the oral cavity.
Dr. Mostoslavsky research goal is to advance our understanding of stem cell biology with a focus on their genetic manipulation via gene transfer and their potential use for stem cell-based therapy. By discovering the mechanisms involved in stem cell self-renewal and differentiation it will be possible to manipulate stem cell fate and use it as the basis for the correction of several diseases. Projects in the Mostoslavsky lab focus on the use of different stem cell populations, including embryonic and induced Pluripotent stem cells, hematopoietic stem cells and intestinal stem cells.
