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Faculty Detail    
Name KEVIN L KIRK
  
Campus Address MCLM 308 Zip 0005
Phone  205-934-3122
E-mail  klkirk@uab.edu
Other websites
     


Faculty Appointment(s)
Appointment Type Department Division Rank
Primary  Cell, Developmntl, & Integrative Biology  Cell, Developmntl, & Integrative Biology Professor
Center  GL Ctr for Craniofacial, Oral, & Dental Disorders  GL Ctr for Craniofacial, Oral, & Dental Disorders Professor

Graduate Biomedical Sciences Affiliations
Cellular and Molecular Biology Program 
Hughes Med-Grad Fellowship Program 
Integrative Biomedical Sciences 
Neuroscience 
Pathobiology and Molecular Medicine 
Waiting to be Seated 

Biographical Sketch 
Kevin L. Kirk (b. 1954), Professor, completed undergraduate studies in Psychobiology at Luther College in Decorah, Iowa (B.A., 1976) and did graduate work in Physiology and Biophysics at the University of Iowa (Ph.D., 1981). He came to UAB in 1981 as a postdoctoral fellow and joined the Department of Physiology and Biophysics in 1984.   Dr. Kirk has received several awards for his research including the Karlin Henze Memorial Award for Cystic Fibrosis Research; a Searle Scholar Award and an Established Investigatorship from the American Heart Association.

Society Memberships
Organization Name Position Held Org Link
American Physiological Society     
Biophysical Society     
 



Research/Clinical Interest
Title
The CFTR Chloride Channel
Description
Our research centers on the epithelial chloride channel (CFTR) that is encoded by the gene that is defective in cystic fibrosis. This chloride channel is implicated in two major human diseases: cystic fibrosis (low CFTR activity in lung) and secretory diarrhea (excessive CFTR activity in gut). We have identified novel CFTR binding proteins that govern the functional activity of this chloride channel in epithelial tissues. In addition, we are investigating how CFTR channel gating is controlled by interactions among the various cytoplasmic domains of this ion channel. Each of these interactions is a potential target for physiologic and pharmacologic manipulation of CFTR channel activity. By defining the functional relevance and structural basis of each of these intermolecular and intramolecular interactions, we hope to develop new strategies for treating diseases such as cystic fibrosis and diarrhea.

Selected Publications 
Publication PUBMEDID
Naren, A.P., M.W. Quick, J. Collawn, D.J.Nelson and K.L. Kirk. Syntaxin 1A inhibits CFTR chloride channel via domain-specific protein-protein interactions. Proc. Natl. Acad. Sci. USA 95:10972-10977, 1998.  9724814 
Naren, A.P., D.J. Nelson, W. Xie, B. Jovov, J. Pevsner, M.K. Bennett, D.J. Benos, M.W. Quick and K.L. Kirk. Regulation of CFTR chloride channels by syntaxin and Munc-18 isoforms. Nature 390:302-305, 1997.  9384384 
Jilling, T. and K. L. Kirk. Cyclic AMP and chloride-dependent regulation of the apical constitutive secretory pathway in colonic epithelial cells. J. Biol. Chem. 271:4381-4387, 1996.  8626788 
Kirk, K.L. and Wang, W. A unified view of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gating: combining the allosterism of a ligand-gated channel with the enzymatic activity of an ATP-binding cassette (ABC) transporter. J. Biol. Chem. 286: 12813-12819, 2011.  21296873 
Wang, W., J. Wu, K. Bernard, G. Li, G. Wang, M.O. Bevensee and K.L. Kirk. ATP-independent CFTR channel gating and allosteric modulation by phosphorylation. Proc. Natl Acad. Sci USA. 107:3888-3893, 2010  20133716 
Bernard, K., W. Wang, R. Narlawar, B. Schmidt and K.L. Kirk. Curcumin cross-links cystic fibrosis transmembrane conductance regulator (CFTR) polypeptides and potentiates CFTR channel activity by distinct mechanisms. J. Biol. Chem. 284:30754-30765, 2009.  19740743 
Wang, W., K. Bernard, G. Li and K.L. Kirk. Curcumin opens CFTR channels by a novel mechanism that requires neither ATP binding nor dimerization of the nucleotide binding domains. J. Biol Chem 282(7): 4533-4544, 2007.   17178710 
Wang, W., G. Li, J.P. Clancy and K.L. Kirk. Activating CFTR chloride channels with pore blocker analogs. J. Biol. Chem. 280(25): 23622-23630, 2005  15857825 
Wang, W., C. Oliva, A. Holmgren, C. H. Lillig and K.L. Kirk. Reversible silencing of CFTR channels by glutathionylation. J. Gen. Physiol. 125:1-16, 2005.  15657297 
Cormet-Boyaka, E, M Jablonsky, AP Naren, PL Jackson, DD Muccio and KL Kirk. Rescuing cystic fibrosis transmembrane conductance regulator(CFTR)-processing mutants by transcomplementation. Proc. Natl. Acad. Sci. 101(21): 8221-8226, 2004.  15141088 
Bradbury, N., T. Jilling, G. Berta, E. Sorscher, R. Bridges and K.L. Kirk. Regulation of plasma membrane recycling by CFTR. Science 256:530-532, 1992.  1373908 
Ganeshan R., A Di, DJ Nelson, MW Quick and KL Kirk. The interaction between syntaxin 1A and Cystic Fibrosis Transmembrane Conductance Regulator Cl- channels is mechanistically distinct from syntaxin 1A-SNARE interactions. J. Biol. Chem. 278(5):2876-2885, 2003  12446687 
Estelle Cormet-Boyaka, Anke Di, Steven Y. Chang, Anjaparavanda P. Naren, Albert Tousson, Deborah J. Nelson, and Kevin L. Kirk. CFTR chloride channels are regulated by a SNAP-23/syntaxin1A complex. Proc. Natl. Acad. Sci. 99 (19): 12477-12483,2002.  12209004 
Fu, J., H.J.Li, A.P. Naren and K.L. Kirk. A cluster of negative charges at the amino terminal tail of CFTR regulates ATP dependent channel gating. J. Physiol. 536(2):459-470,2001.  11600681 
Fu, J. and K.L. Kirk. Cysteine scanning mutagenesis reveals dual regulatory roles of the amino terminal tail of CFTR in controlling ATP-dependent channel gating. J. Biol. Chem. 276(38):35668,2001.  11468285 
Naren, A.P., A. Di, E. Cormet-Boyaka, P.N. Boyaka, J. McGhee, W. Zhou, J.F. Englehardt, K. Akagawa, T. Fujiwara, T. Ullrich, S., Matalon, D.J. Nelson and K.L. Kirk. Syntaxin 1A is expressed in native airway epithelial cells where it modulates CFTR Cl- -currents. J. Clin. Invest. 105(3): 377-386,2000.  10675364 
Naren, A.P., Cormet-Boyaka, J. Fu, M. Villian, E. Blalock, M. Quick, and K.L. Kirk. CFTR Cl channel regulation by an interdomain interaction. Science 286:544-548, 1999.  10521352 
 

Keywords
cystic fibrosis, CFTR, ion channel, diarrhea, protein-protein interactions, patch clamping, electrophysiology, ABC transporters