
The University of Chicago
5841 South Maryland, MC 1089
Chicago, IL 60637
773-702-2433
773-834-5251 (fax)
jturner@bsd.uchicago.edu
Committee on Cell Physiology
Committee on Molecular Medicine
Committee on Molecular Metabolism and Nutrition
Cancer Research Center
Graduate Program in Molecular Pathogenesis & Molecular Medicine
Gastrointestinal pathology with emphasis on inflammatory bowel disease.
Epithelia of the intestines, kidneys, and lungs must balance absorptive and secretory transport with the maintenance of a mucosal barrier. Transport across these epithelia, which is necessary for life, occurs both through and between cells. The route between cells, also known as the paracellular pathway is regulated by the tight junction. Our laboratory has primarily used the intestine as a model system in which to study tight regulation of junction and coordination of active transcellular and paracellular transport.
In general, the approaches used are vertically-integrated and include biochemical analysis of regulatory and structural proteins, cell biology of tight junction assembly and membrane traffic, and mechanisms and pathophysiological impact of tight junction dysfunction to overall health. Recent work has focused on the role of the epithelium in the interplay between the mucosal immune system and luminal microbes. A broad range of advanced techniques based on molecular genetic, proteomic, and morphologic, and functional analysis of cultured cells, transgenic animals, and human tissues are employed.
Tight junction structure. A major are of interest is to elucidate the basic structures that defines the tight junction. Which proteins make up the tight junction? What is the role of specialized lipid domains? How do proteins and lipids interact to form a paracellular barrier that also allows passage of some molecules in a charge- and size-specific manner? These questions are being addressed using fluorescent fusion proteins expressed in cultured cells and mouse intestine studied by live cell and live animal imaging techniques.
Mechanisms of cytoskeletal regulation. A second major area of interest focuses on actomyosin and myosin light chain kinase. These studies have led to the identification of novel patterns of gene regulation and alternative splicing that are closely related to cell differentiation and specialized function in health and disease.
Role of tight junction dysregulation in disease. One other major area of investigation is mechanisms tight junction regulation secondary to physiological, pharmacological, and pathophysiological stimuli. This work uses a broad array of technologies and has led to novel insight into epithelial contributions to normal homeostasis as well as development of novel drugs that are currently in pre-clinical trials for inflammatory bowel disease and graft versus host disease.