Michael Welsh, M.D. (Full Member)
Professor of Internal Medicine, University of Iowa, Iowa City, IA
Professor of Physiology and Biophysics, University of Iowa, Iowa City, IA
Investigator, Howard Hughes Medical Institute, Iowa City, IA
Consultant, Veterans Administration Hospital, Iowa City, IA

http://www.int-med.uiowa.edu/Divisions/Pulmonary/Directory/MichaelWelsh.html

Research Interest    

Dr. Welsh has a long-standing interest in the study and treatment of cystic fibrosis. His laboratory is using a multi-faceted approach to understand the biology of cystic fibrosis, with several areas of emphasis. The first is an investigation of the structure and function of CFTR. Specifically, the laboratory is using a combination of genetic, biochemical, and electrophysiologic techniques to examine both the mechanisms that allow CFTR to form a Cl- channel and how opening and closing of the channel are regulated. The second area of emphasis is an exploration of how cystic fibrosis-associated mutations cause CFTR to malfunction and how that malfunction causes disease. In focusing on the pathogenesis of airway disease, the laboratory has developed the hypothesis that altered salt concentrations in the airway surface liquid may interfere with the killing of inhaled bacteria by inhibiting the function of defensins and other antibacterial molecules. This has led to an ongoing program that evaluates antibacterial factors in the airway fluid, as well as mechanisms that lead to bacterial biofilm formation in the CF airway. The third focus area is the development of new approaches to therapy, with emphasis on 1) gene transfer involving adenoviral and adeno-associated viral vectors, and 2) the study of cellular and molecular mechanisms that limit gene transfer to airway epithelia. Using knowledge obtained from those studies, the Welsh group has developed novel strategies that increase the efficiency of gene transfer to airway epithelia. Fourth, the Welsh laboratory is analyzing a novel family of non-voltage gated cation channels that are found in epithelia and in the nervous system. With respect to epithelia, the group is studying the role of ENaC in epithelial electrolyte transport and the consequences of ENaC dysfunction in genetic forms of hypertension and hypotension. Dr. Welsh's group also recently developed a porcine model of cystic fibrosis that will aid in the understanding of CF lung pathogenesis and the development of gene therapies.

Selected Publications:

Farmen SL, Karp PH, Ng P, Palmer DJ, Koehler DR, Hu J, Beaudet AL, Zabner J, and Welsh MJ. Gene Transfer of CFTR to Airway Epithelia: Low Levels of Expression are Sufficient to Correct Cl Transport and Overexpression can Generate Basolateral CFTR. Am. J. Physiol. 280:L1123-L1130, 2005.

Ostedgaard LS, Rogers CS, Dong Q, Randak CO, Vermeer DW, Rokhlina T, Karp PH, and Welsh MJ. Processing and Function of CFTR-∆F508 Are Species-Dependent. Proc. Natl. Acad. Sci. USA, 104:15370-15375, 2007

Liu, L, Li, Y, Wang, R, Yin, C, Dong, Q, Hing H, Kim C, and Welsh MJ. Drosophila Hygrosensation Requires the TRP Channels Water Witch, Nanchung, and Inactive. Nature, 450(7167):294-298, 2007.

Rogers, CS, Hao Y, Rokhlina T, Samuel M, Stoltz DA, Yi Y, Petroff E, Vermeer DW, Kabel AC, Yan Z, Spate L, Wax D, Murphy CN, Rieke A, Whitworth K, Linville ML, Korte SW, Engelhardt JF, Welsh MJ, and Prather RS. Production of CFTR Null and ∆F508 Heterozygous Pigs by AAV-Mediated Gene Targeting and Somatic Cell Nuclear Transfer. J. Clin. Invest., In Press, 2008.

Shah AS, Farmen SL, Moninger TO, Businga TR, Andrews MP, Bugge K, Searby CC, Nishimura D, Brogden KA, Kline JN, Sheffied VC, and Welsh MJ. Loss of Badet Biedl Syndrome Proteins Alters the Morphology and Function of Motile Cilia in Airway Epithelia. Proc. Natl. Acad. Sci. USA, 105(9):3380-5, 2008.

Publications from Gene Therapy Center

Publications from PubMed