Jonathan A. Cohn, MD

Department / Division:
Medicine / Gastroenterology

Address:
DUMC 3378
Durham, NC 27710

Office Telephone:
919-684-6879

Fax Telephone:
919-684-4983

• MD, Weill Cornell Medical College (New York), 1978

• Medicine, University of Alabama at Birmingham, 1978-1980
• Medicine, University of California, San Francisco, 1980-1981

• Gastroenterology, Yale Medical Center (Connecticut), 1981-1984

Clinical Interests:
Pancreatitis, GI aspects of cystic fibrosis

Research Interests:
In many epithelial tissues, the protein mainly responsible for controlling transepithelial fluid movement is the the cystic fibrosis transmembrane conductance regulator (CFTR).  CFTR was originally identified as the protein product of the gene causing cystic fibrosis (CF).  CFTR functions as a chloride channel regulated by protein kinase A (PKA).  This laboratory is studying the role and regulation of CFTR.  One project focuses on how PKA acts on CFTR.  In this project, recombinant peptide models are being used to model the cytoplasmic domains of CFTR responsible for activating the protein's chloride's chloride channel function.  Site-directed mutagenesis is being used to produce modified peptides to study how different individual serine phosphoryation contribute to CFTR regulation.  A second project concerns DF508, the most common mutation among patients with CF.  This mutation affects CFTR function by preventing normal folding and intracellular trafficking of the newly synthesized mutant protein.  This project is examining the mislocalization of DF508-CFTR in tissues and cell lines with the long term goal of developing strategies to prevent the mutant protein from mislocalizing.  A third project concerns the role of CFTR in chronic pancreatitic diseases.  Emerging data about the role of CFTR during normal pancreatic secretion suggests that dysfunction of this protein may lead to pancreatic diseases such as chronic pancreatitis and pancreatic cancer.  Patients with these chronic pancreatic diseases are being tested for CFTR mutations and for evidence of defective CFTR function.

Representative Publications:
Howell LD, Borchardt R, Kole J, Kaz AM, Randak C, Cohn JA. Protein kinase A regulates ATP hydrolysis and dimerization by a CFTR (cystic fibrosis transmembrane conductance regulator) domain. Biochem J. 2004 Feb 15;378(Pt 1):151-9. (2004) Abstract

Noone PG, Zhou Z, Silverman LM, Jowell PS, Knowles MR, Cohn JA. Cystic fibrosis gene mutations and pancreatitis risk: relation to epithelial ion transport and trypsin inhibitor gene mutations. Gastroenterology. 2001 Dec;121(6):1310-9. (2001) Abstract

Cohn JA, Friedman KJ, Noone PG, Knowles MR, Silverman LM, Jowell PS. Relation between mutations of the cystic fibrosis gene and idiopathic pancreatitis. N Engl J Med. 1998 Sep 3;339(10):653-8. (1998) Abstract

Fitz JG, Basavappa S, McGill J, Melhus O, Cohn JA. Regulation of membrane chloride currents in rat bile duct epithelial cells. J Clin Invest. 1993 Jan;91(1):319-28. (1993) Abstract

Cohn JA, Strong TV, Picciotto MR, Nairn AC, Collins FS, Fitz JG. Localization of the cystic fibrosis transmembrane conductance regulator in human bile duct epithelial cells. Gastroenterology. 1993 Dec;105(6):1857-64. (1993) Abstract

Marino CR, Matovcik LM, Gorelick FS, Cohn JA. Localization of the cystic fibrosis transmembrane conductance regulator in pancreas. J Clin Invest. 1991 Aug;88(2):712-6. (1991) Abstract