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Developmental Responses to Early Intestinal Invaders
W. Allan Walker, MD, founded the Mucosal Immunology and Developmental Gastroenterology Laboratories—renamed the Mucosal Immunology and Biology Research Center—in the 1990s as part of the Gastroenterology and Nutrition Division at MGHfC at Harvard Medical School.
His research efforts include defining the passive and active protective properties of human breast milk with regard to protection from disease during the newborn period. Dr. Walker also studies the development of human intestinal host defenses using human fetal organ cultures, cell lines, and xenograft transplant models.
Specifically, the Laboratory of W. Allan Walker, MD at Massachusetts General Hospital 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. More recently, they have studied the effect of initial colonizing microbiota on the development of mucosal protective function and the mechanism of probiotics in this process.
Dr. Walker’s laboratory has been one of the leading laboratories in the study of developmental changes of intestinal host defense in response to invading microorganisms and their toxins.
Studies in animal models and recent studies in human fetal intestinal models suggest that, under certain circumstances, the immature human enterocyte is not able to protect against bacteria, or it responds inappropriately to microbes and enterotoxins.
This inappropriate response may be central to the pathophysiology of age-related infectious gastrointestinal diseases. Recent exciting results indicate that the inability of the immature gut to discriminate between commensal and pathologic may be related, at least in part, to reduced expression of IkB by the immature enterocyte.
Dr. Walker’s laboratory focuses on identifying the mechanisms of developmental regulation of enterocyte responses to colonizing intestinal bacteria and their products. Researchers in the Walker lab also examine the role of Toll-like receptors in this response.
These studies are undertaken in collaboration with Drs. Pothoulakis and McCormick and Dr. Ciarán Kelly, director of gastroenterology training and medical director of the Celiac Center at Beth Israel Deaconess Medical Center in Boston, Massachusetts.
W. Allan Walker, MD
Physician Investigator, Mucosal Immunology and Biology Research Center, Massachusetts General Hospital
Professor of Pediatrics, Harvard Medical School
Conrad Taff Professor of Nutrition, Harvard Medical School
Director, Division of Nutrition, Harvard Medical School
Professor of Nutrition, Harvard School of Public Health
Kriston Ganguli, MD, Instructor of Pediatrics
Di Meng, MD, PhD, Instructor of Pediatrics
Weishu Zhu, MD, Instructor of Pediatrics
Katherine Gregory, PhD, RN, Instructor in Pediatrics, Brigham and Women's Hospital