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Principal
Investigators
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Principal Investigators
Bobby Cherayil, MD 
Associate Professor of Pediatrics
Research in my laboratory is directed at elucidating the molecular mechanisms involved in innate immunity to Salmonella, an enteric bacterial pathogen that causes both intestinal and systemic disease in humans. We are particularly interested in the role played by enterocytes, macrophages and NK cells in inflammatory and anti-microbial responses. Using in vitro cell culture experiments, as well as in vivo models of intestinal and systemic salmonellosis, we are attempting to identify the bacterial and host molecules that contribute to these responses.
Research • Curriculum Vita
Fellows: C.V. Srikanth
Verena Göbel , MD
Assistant Professor of Pediatrics
My laboratory studies epithelial morphogenesis and growth regulation in Caenorhabditis elegans. One of our objectives is to contribute to the understaning of the molecular basis of intestinal morphogenesis. C. elegans is a transparent roundworm whose internal organs are formed by different types of tubes constructed from distinct, yet simple, polarized epithelia. The simplicity of this organism when combined with its sophisticated genetic resources make it a powerful tool to examine tubulogenesis. We have recently identified a number of cytoskeletal genes that are required to build the apical/luminal and basolateral membranes of the intestine and other tubular organs. We are currently using forward and reverse genetic approaches, along with high-resolution microscopic techniques to determine the morphogenetic role of these genes, and we continue to devise strategies to identify additional novel molecules involved in these processes.
Research • Curriculum Vita
 Ciarán P. Kelly, MD
Associate Professor of Medicine
My research focuses on the pathogenesis of gastrointestinal infectious and inflammatory disorders. I have a longstanding interest in the host immune response to Clostridium difficile, the etiologic agent of antibiotic-associated diarrhea and pseudomembranous colitis. My research has shown that a systemic humoral immune response to C. difficile toxin A is associated with natural protective immunity against it. This important finding has opened the way to the development and testing of novel passive and active immunization regimens to prevent and treat C. difficile diarrhea and colitis.
Research • Curriculum Vita
Fellows: Xinhua Chen
 Beth McCormick, PhD
Associate Professor of Pediatrics
My work is focused on the molecular mechanisms by which the enteric pathogens Salmonella typhimurium and Shigella flexneri induce mucosal inflammatory responses. Such inflammatory responses lead to active states of intestinal inflammation and are a hallmark feature of the disease pathophysiology of inflammatory bowel diseases such as bacterial enterocolitis, Crohn’s Disease, and ulcerative colitis. My original interest in this field of research led to the development of a novel model system to examine the immunopathology of intestinal inflammation in vitro. My findings from these studies were the first to demonstrate that a pro-inflammatory program, which could recruit inflammatory cells (neutrophils), was orchestrated by epithelial cells in response to enteric pathogens. This work led to the identification of distinct chemokines released from intestinal epithelial cells, which work in concert to direct neutrophil movement into the intestinal lumen in response to enteric pathogens. Research projects in my laboratory are now directed at unraveling the molecular nature of these signals.
Research • Curriculum Vita
Fellows: Bryan Hurley, Karen Mumy, Dario Siccardi, Daniel Wall
 Nanda Nanthakumar, PhD
Assistant Professor of Pediatrics
The adult human gastrointestinal tract is colonized by a community of more than 450 interdependent species of bacteria that are the major components of a stable but dynamic microbial ecosystem known as the gut microbiota. The gut microbiota are now becoming recognized as part of an important mutualist relationship in which both the microbes and humans benefit. Mutualist association requires cross communication (crosstalk) between the microbiota and the epithelial lining of the gut. My lab focuses on the interaction between gut epithelium and gut microbiota in the newborn, during the transition from milk to solid food, and in mature young adults.
Research • Curriculum Vita
Fellows: Di Meng, Weishu Zhu
 David Newburg, PhD
Associate Professor of Pediatrics
The program in glycobiology, under the direction of Dr. David Newburg, studies biologically active glycans relevant to developmental mucosal immunology. For example, this program discovered that the human milk glycans constitute an innate immune system whereby the mother, through her milk, protects her infant from disease during infancy. Glycans include glycoproteins, glycolipids, glycopeptides, glycosaminoglycans, mucins, and oligosaccharides. They are expressed in especially high amounts on the cell surface, especially the intestinal mucosal cell surface. Such glycans are important in cellular communication, but they are also used by many pathogens to identify, bind and infect their host target cell. Human milk is especially rich in glycans, and many of the human milk soluble glycans inhibit pathogens by inhibiting their ability to bind to their host cell receptors. This human milk research is part of a longstanding collaboration with Dr.Guillermo Ruiz-Palacios in Mexico City, and Dr. Ardythe Morrow in Cincinnati. The Glycobiology program specializes in developing new methods by using state-of-the-art technology for the analysis of glycans, for measuring their metabolism, and for determining genetic control mechanisms of their expression. The program also measures biologically active glycans from exogenous sources, such as probiotics, in collaboration with Ciaran Kelly, and botanicals. This program also works closely with Dr. Nanda Nanthakumar in defining the ontogeny of glycans in the intestinal mucosa, and their relationship to inflammatory bowel diseases.
Research • Curriculum Vita
Fellows: Alix Dubert-Ferrandon, Nathan Bao
 Charalabos (Harry) Pothoulakis, MD
Professor of Medicine
Dr. Pothoulakis is a Professor of Medicine at Harvard Medical School and a member of the Division of Gastroenterology at BIDMC, and the Division of Pediatric Gastroenterology and Nutrition at MGH. He graduated from the Aristotelian University of Thessaloniki Medical School in Greece and, following his medical internship and residency, he joined the Division of Gastroenterology at Boston University Medical Center as a Research Fellow in 1982. After completion of his fellowship he became a faculty member at the Department of Medicine at Boston University School of Medicine and then joined the Beth Israel Medical Center in 1990 as a Senior Research Associate and an Assistant Professor at Harvard Medical School. Dr. Pothoulakis’ research program is primarily focused on the role of neuropeptides and hormones in several disease states, including Clostridium difficile infection, inflammatory bowel disease, and irritable bowel syndrome. His recent projects also involve the neuropeptide-dependent mechanisms by which communication between the intestinal mucosa and the fat depots affect the pathogenesis of intestinal inflammation. In 2003 he established a "Gastrointestinal Neuropeptide Center" in the Division of Gastroenterology at Beth Israel Deaconess Medical Center that involves a multi-disciplinary approach to study neuropeptide function in the GI tract. Dr. Pothoulakis has been as been actively involved in training of fellows in basic sciences in GI-related research themes. He is an author of over 100 original articles and numerous reviews and book chapters and serves in the Editorial Board of several biomedical journals, including Gastroenterology, and American Journal of Physiology. He is also a member of Hormones, Transmitters, Growth Factors and Their Receptors, and Immunology, Microbiology, and Inflammatory Bowel Disease Sections of the American Gastroenterological Association. Dr. Pothoulakis is the recipient of the highly prestigious "Janssen Award in Basic Research in Gastrointestinal Motility" awarded by the American Gastroenterological Association in recognition of his discoveries and insights into the function of gastrointestinal neuropeptides. Dr. Pothoulakis’ research projects are currently funded by three RO-1 grants from the National Institute of Health. He is also the Director of a NIH Program Project grant that examines the barrier function of the GI Tract in health and disease.
Research • Curriculum Vita
 Hai Ning Shi, DVM, PhD
Assistant Professor of Pediatrics
My research interests are focused on the pathogenesis and immune regulation of intestinal inflammation. We are particularly interested in exploring the mechanisms by which the helminth parasite modulates intestinal mucosal response to enteric bacteria and bacteria-associated intestinal inflammation using a co-infection model system. We also examine the impact of intestinal colonization of bacteria (probiotics) at early life on the development and regulation of mucosal T cell responses (Th1, Th2 and T regs) and explore the mechanisms by which probiotics modulate host protection against enteric pathogens. Using both in vivo and in vitro approaches, we also examine and define the conditions under which dysregulation of intestinal mucosal response to luminal antigen triggers the development of intestinal inflammatory responses that ultimately result in chronic inflammatory disease. Our research will provide greater insight about how intestinal microorganisms may alter the regulatory mechanisms of mucosal immunity, which may be instrumental in the establishment of effective preventive and therapeutic approaches for the treatment of Th1 and Th2 mediated diseases and for the design of effective intestinal vaccines.
Research • Curriculum Vita
Fellows: Ondulla Foye-Jackson
 W. Allan Walker, MD
Professor of Pediatrics, Chief
My primary responsibilities at Massachusetts General Hospital involve overseeing the Mucosal Immunology and Developmental Gastroenterology Laboratories at Building 114 MGH-East as part of the Combined Program in Pediatric Gastroenterology and Nutrition at Harvard Medical School. These laboratories have nine principal investigators, ten postdoctoral fellows and two graduate students who study oral tolerance, gut inflammation and microbial-epithelial "crosstalk." My research efforts include defining the passive and active protective properties of human breast milk with regard to the protection from disease during the newborn period. I also study the development of human intestinal host defenses using human fetal organ cultures, cell lines, and xenograft transplant models. Specifically, my laboratory has reported that the human fetal epithelium responds inappropriately to both endotoxin and exotoxins, which helps to explain an increased incidence and severity of certain inflammatory and secretory diarrheas in this age group.
Research • Curriculum Vita
Fellows: Lei Lu, Meiqian Weng, Ilse Broekaert
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