Nusrat and Parkos Laboratories
Emory Epithelial Pathobiology Unit
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Charles Parkos, MD PhD |
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Professor and Vice Chair Director, Experimental Pathology Director, Division of Gastrointestinal Surgical Pathology Director, Medical Scientist Training Program Graduate Programs: Immunology and Molecular Pathogenesis (IMP) Email: cparkos@emory.edu Research interests: Many inflammatory disorders are characterized by infiltration of leukocytes across epithelial (mucosal) surfaces resulting in disruption of the critical barrier that protects from contamination by microbes and noxious agents. Examples of such disorders include inflammatory bowel disease (Crohn's and ulcerative colitis), gastritis, asthma, bronchits, and cystitis. While controversy exists as to the initiating events responsible for many of these conditions, it is clear that altered epithelial permeability and increased infiltration of leukocytes in the affected mucosa are key processes that contribute to disease symptoms and pathophysiology. A long term objective of our group is to identify novel tissue-targeted therapeutics directed at decreasing deleterious effects of dysregulated mucosal inflammation and altered epithelial permeability. Conversely, therapeutics directed at manipulating epithelial permeability will aid in developing targeted drug and vaccine delivery. Key projects in the Parkos lab include: 1) Identification of novel adhesive ligands that regulate leukocyte migration across the epithelium. 2) Understanding the role of tight junction immunoglobulin superfamily members in regulation of epithelial barrier function and leukocyte transmigration. Current specific projects focus on:     a.Structural and molecular basis of Junctional Adhesion Molecule A (JAM-A, previously termed JAM-1) function.     b. Functional characterization of novel JAM-like proteins.     c. Characterization of novel Coxsackie Adenovirus Receptor (CAR)-like proteins.     d. Use of rational drug design to develop inhibitors of JAM function for use in therapeutics. 3) Elucidation of the role of a ubiquitously expressed membrane protein termed CD47 and Toll-like Receptors in the regulation of leukocyte migration and epithelial function. 4) Understanding the structural basis of CD47 binding to the inhibitory receptor Signal Regulatory Protein Alpha (SIRP-alpha). 5) Characterization of signaling events between leukocytes and epithelial cells that serve to regulate leukocyte transmigration by altering epithelial permeability. Grants:  Link to Current Grants List of Active Grant Support -P.I., National Institutes of Health, “Neutrophil interactions with intestinal epithelium,” RO1-DK72564 (Previously HL54229), 1995-2010. -P.I., National Institutes of Health, "Structure function studies on intestinal epithelial JAM" R01-DK61379, 2002-2012. -P.I., National Institutes of Health, "Intestinal Inflammation: Signaling proteins and the rate of PMN transmigration" R01 DK079392 (previously HL72124), 2003-2112. -P.I. National Institutes of Health, “Pathobiology of mucosal/epithelial disease” T32 DK007771, 2006-2011. -P.I. National Institutes of Health, “Emory Medical Scientist Training Program” T32 GM008169-21, 1987-2012. -Co P.I., National Institutes of Health “Emory epithelial pathobiology research development grant.” R24 DK064399 (P.I. Vincent Yang) 2003-2113. |
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