Jonathan Allen Cohn, MD

Professor of Medicine
Associate Professor of Cell Biology
Professor in Pediatrics
Campus mail DUMC Box 3256, Durham, NC 27710
Phone (919) 684-6879
Email address jonathan.cohn@duke.edu

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.

Education and Training

  • Fellow in Gastroenterology, Medicine, Yale University, 1981 - 1984
  • Medical Resident, Medicine, University of California San Francisco, School of Medicine, 1980 - 1981
  • Medical Resident, Medicine, University of Alabama Birmingham, 1978 - 1980
  • M.D., Cornell University, 1978

Publications

Boujaoude, L. C., C. Bradshaw-Wilder, C. Mao, J. Cohn, B. Ogretmen, Y. A. Hannun, and L. M. Obeid. “Cystic fibrosis transmembrane regulator regulates uptake of sphingoid base phosphates and lysophosphatidic acid: modulation of cellular activity of sphingosine 1-phosphate.” J Biol Chem 276, no. 38 (September 21, 2001): 35258–64. https://doi.org/10.1074/jbc.M105442200.

PMID
11443135
Full Text

Blaug, S., K. Hybiske, J. Cohn, G. L. Firestone, T. E. Machen, and S. S. Miller. “ENaC- and CFTR-dependent ion and fluid transport in mammary epithelia.” Am J Physiol Cell Physiol 281, no. 2 (August 2001): C633–48. https://doi.org/10.1152/ajpcell.2001.281.2.C633.

PMID
11443063
Full Text

Kole, Jolanta, S. Gary Mansfield, M. Puttaraju, Mariano A. Garcia-Blanco, Lloyd G. Mitchell, and Jonathan A. Cohn. “Production of functional CFTR from mutant CFTR mRNA repaired by targeted RNA trans-splicing.” Gastroenterology 120, no. 5 (April 2001): A24–A24. https://doi.org/10.1016/s0016-5085(08)80118-7.

Full Text

Howell, L Daniel, Melissa E. Danko, Roy Borchardt, Christoph Randak, and Jonathan A. Cohn. “Domain-domain interactions regulate ATP hydrolysis during CFTR activation.” Gastroenterology 120, no. 5 (April 2001): A84–A84. https://doi.org/10.1016/s0016-5085(08)80416-7.

Full Text

Cohn, J. A. “The diagnosis of CF in patients with non-classical phenotypes.” Pediatric Pulmonology 30, no. SUPPL. 20 (December 1, 2000): 89–90.

Scholars@Duke

Mansfield, S. G., J. Kole, M. Puttaraju, C. C. Yang, M. A. Garcia-Blanco, J. A. Cohn, and L. G. Mitchell. “Repair of CFTR mRNA by spliceosome-mediated RNA trans-splicing.” Gene Ther 7, no. 22 (November 2000): 1885–95. https://doi.org/10.1038/sj.gt.3301307.

PMID
11127576
Full Text

Howell, L. D., R. Borchardt, and J. A. Cohn. “ATP hydrolysis by a CFTR domain: pharmacology and effects of G551D mutation.” Biochem Biophys Res Commun 271, no. 2 (May 10, 2000): 518–25. https://doi.org/10.1006/bbrc.2000.2659.

PMID
10799328
Full Text

Cohn, J. A., J. D. Bornstein, and P. S. Jowell. “Cystic fibrosis mutations and genetic predisposition to idiopathic chronic pancreatitis.” Med Clin North Am 84, no. 3 (May 2000): 621–ix. https://doi.org/10.1016/s0025-7125(05)70245-5.

PMID
10872419
Full Text

Cohn, Jonathan A., Jeffrey D. Bomstein, Paul S. Jowell, Peadar G. Noone, Zhaoqing Zhou, M. S. Branch, John Baillie, William R. Treem, Michael R. Knowles, and Lawrence M. Silverman. “Molecular pathogenesis of chronic pancreatitis associated with abnormal CFTR genotypes.” Gastroenterology 118, no. 4 (April 2000): A159–A159. https://doi.org/10.1016/s0016-5085(00)82713-4.

Full Text

Mansfield, S. G., J. Kole, M. Puttaragu, C. C. Yang, M. A. Garcio-Blanco, L. G. Mitchell, and J. A. Cohn. “Repair of mutant CFTR mRNA by targeted RNA trans-splicing.” In Gastroenterology, 118:A185–A185. Elsevier BV, 2000. https://doi.org/10.1016/s0016-5085(00)82817-6.

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