Jerrold Turner, M.D., Ph.D.


Primary:

Professor, Pathology
Associate Chairman for Academic Affairs


Secondary:

Committee on Cellular and Molecular Physiology
Committee on Molecular Medicine

Education:

Degree Year Institution Area
AB & AM

1984

Washington University, St. Louis

Biology
PhD

1990

Case Western Reserve University, Cleveland, OH

Cell Biology
MD

1991

Case Western Reserve University, Cleveland, OH

Medicine
Postdoc

1991-1996  

Harvard Med. - Brighham & Women's, Boston, MA

Cell Physiol.-Pathophys.



Phone: (773) 702-2433 /  Fax: (773) 834-5241 /  Lab: (773) 702-4869
E-Mail: jturner@bsd.uchicago.edu
Address: AMB P526 (MC 1089) / Lab: AMB P516/P513

Web page:
http://pathologyweb.bsd.uchicago.edu
http://pathology.bsd.uchicago.edu/faculty/turner.htm


Research Summary 

Research Synopsis:

Transporting epithelia, such as those found in the intestines, kidneys, and lungs, must balance absorptive and secretory transport with the maintenance of a relatively impermeant barrier.  Passive transport across this barrier occurs between cells and is regulated by the tight junction, the rate-limiting determinant that restricts passage of hydrophilic solutes based on size and charge. Dysregulation of barrier function has been associated with a variety of intestinal and extra-intestinal diseases.

Dr. Turner's laboratory has primarily used the intestine as a model system in which to study the coordinated regulation of transcellular and paracellular transport, with mechanisms of this regulation and its disruption in disease the major focus of the research efforts. To this end Dr. Turner's laboratory uses a broad range of advanced techniques based on molecular genetic, proteomic, and morphologic, and functional analysis of cultured cells, transgenic animals, and human tissues.

There are three major areas of investigation in Dr. Turner's laboratory. The first focuses on tight junction regulation secondary to physiological, pharmacological, and pathophysiological stimuli using the full array of technologies listed above. Recent work has pioneered live cell imaging using fluorescent fusion constructs of tight junction proteins expressed in cell lines and transgenic animals.

The second major area of interest focuses on cytoskeletal regulation of cellular function, with particular emphasis 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.

The third major area of investigation takes advantage of discoveries in the first two areas to better understand pathogenesis of intestinal disease. For example, several peptides and small molecules have been rationally-designed to modulate key regulatory events. These are being tested for their ability to prevent or treat disease in models of intestinal disease using genetically-modified mice.


Selected Publications

Clayburgh, D.R., Rosen, S., Witkowski, E.D., Wang, F., Blair, S., Dudek, S., Garcia, J.G., Alverdy, J.C., and Turner, J.R. A differentiation-dependent splice variant of myosin light chain kinase, MLCK1, regulates epithelial tight junction permeability. J. Biol. Chem., 279:55506-55513, 2004.

Shen, L., and Turner, J.R. Actin depolymerization disrupts tight junctions via caveolae-mediated endocytosis. Mol. Biol. Cell., 16:3919-3936, 2005.

Wang, F., Graham, W.V., Wang, Y., Witkowski, E.D., Schwarz, B.T., and Turner, J.R. Interferon-gamma and tumor necrosis factor-alpha synergize to induce intestinal epithelial barrier dysfunction by up-regulating myosin light chain kinase expression. Am. J. Pathol., 166:409-419, 2005.

Clayburgh, D.R., Barrett, T.A., Tang, Y., Meddings, J.B., Van Eldik, L.J., Watterson, D.M., Clarke, L.L., Mrsny, R.J., and Turner, J.R. Epithelial myosin light chain kinase-dependent barrier dysfunction mediates T cell activation-induced diarrhea in vivo. J. Clin. Invest., 115:2702-2715, 2005.


Blair, S.A., Kane, S.V., Clayburgh, D.R., and Turner, J.R. Epithelial myosin light chain kinase expression and activity are upregulated in inflammatory bowel disease. Lab Invest., 86:191-201, 2006.


Shen, L., Black, E.D., Witkowski, E.D., Lencer, W.I., Guerriero, V., Schneeberger, E.E., and Turner, J.R. Myosin light chain phosphorylation regulates barrier function by remodeling tight junction structure. J. Cell. Sci., 119:2095-2106, 2006.


Turner, J.R. Molecular basis of epithelial barrier regulation: from basic mechanisms to clinical application. Am. J. Pathol., 169:1901-1909, 2006.


Clayburgh, D.R., Musch, M.W., Leitges, M., Fu, Y.X., and Turner, J.R. Coordinated epithelial NHE3 inhibition and barrier dysfunction are required for TNF-mediated diarrhea in vivo. J. Clin. Invest., 116:2682-2694, 2006.


Schwarz, B.T., Wang, F., Shen, L., Clayburgh, D.R., Su, L., Wang, Y., Fu, Y.X., Turner, J.R.. LIGHT signals directly to intestinal epithelia to cause barrier dysfunction via cytoskeletal and endocytic mechanisms. Gastroenterology, 132:2383-94, 2007.

Weber, C.R., and Turner, J.R. Inflammatory bowel disease: is it really just another break in the wall? Gut, 56:6-8, 2007.

Updated 9/21/07.