Martin Kagnoff

Affiliation: UCSD SOM

Professor of Medicine and Pediatrics, Director of the Laboratory of Mucosal Immunology

Biography

Martin Kagnoff is Professor of Medicine and Director of the Laboratory of Mucosal Immunology in the Department of Medicine and a faculty member of the Division of Gastroenterology at the University of California, San Diego. Dr. Kagnoff received his medical training at Harvard Medical School, and subsequent postgraduate training in Gastroenterology and Immunology at Brigham and Women1s Hospital, Harvard Medical School, Cornell School of Medicine, Boston University School of Medicine, and the Salk Institute for Biological Studies. Dr. Kagnoff has received numerous honors and has served as Editor of the Journal of Clinical Investigation, the American Journal of Physiology, and Associate Editor of the Journal of Immunology. He directs a major National Institutes of Health sponsored program project grant that investigates the molecular and cellular nature of microbial-mucosal interactions in the intestinal tract. His research program is focused on the role of the intestinal epithelium in host mucosal defense.

Research Summary

Our laboratory studies the role of the epithelial layer that lines the intestinal tract in innate host defense and in signaling the onset of immune and inflammatory responses in the intestinal mucosa. We view the intestinal epithelium as a key component of a signal transduction system in which microbes and microbial pathogens, that reside in or infect the intestinal tract, interact with the epithelial lining. Those interactions lead to the activation of signal transduction pathways and the upregulated expression of genes whose products signal cells beneath the epithelium that are key for mediating inflammatory and immune reactions. Products of the inflammatory and immune cells in turn feedback on the epithelial cells and alter epithelial cell functions. For example, altered epithelial cell secretion can result in diarrhea, which serves to rid the host of the pathogen, but also causes unpleasant symptoms in the host.

Our laboratory focuses predominately on human model systems and uses both in vitro cell culture and in vivo models to study host responses to microbial pathogens. One example of a human in vivo model is the use of human intestinal xenografts, which are small pieces of human intestine that are transplanted onto the backs of immunodeficient mice. These human xenografts contain an epithelial lining that is strictly of human origin and can be infected with microbial pathogens or microbial toxins that could not otherwise be studied under controlled conditions in humans. This model allows us assess to the very early signaling and gene transcription events that occur in intestinal epithelium in vivo following infection. Another example of an in vivo model system we employ involves mice in which we alter specific signal transduction molecules only in the intestinal epithelium using a genetic approach (i.e., conditional knock-out) and ask questions regarding the effect of that epithelial cell gene deletion on epithelial cell and mucosal function.

A second focus of our laboratory is on epithelial cell wound healing and the role of specific signal transduction pathways in that process. All of the above studies are relevant for understanding the mechanisms that are key in the host response to infection and how immune and inflammatory diseases are regulated in the intestinal tract. Examples of relevant diseases are infections with Salmonella, pathogenic E. coli, Shigella, or Giardia, as well as the inflammatory bowel diseases ulcerative colitis, Crohn1s disease, and celiac disease.

References

References From PubMed (NCBI)