Paul Killen, M.D., Ph.D.
Associate Professor
pkillen@umich.edu
Campus Address:
GEN PATH M7520 MSRBI 0602
1301 Catherine Road
Ann Arbor, Michigan 48109-0602
Phone: 734/747-2921
Departmental Annual Report
Research Interests
Basement membranes are specialized extracellular matrices which provide a substratum for cell attachment and thereby influence the differentiated phenotype of cells. These matrices play an important role in tissue morphogenesis, and the orderly regeneration of tissues following injury. Pathologic accumulations of basement membranes characterize a variety of acquired and hereditary disorders. Despite its biological importance, little is known about basement membrane biosynthesis and its regulation and health and disease. Collagen IV, the major structural component of basement membranes, is composed of several different polypeptide chains which occur uniquely in these matrices. Two of these polypepetides, a 1(IV) and a 2(IV), are the products of a gene cluster on chromosome 13. These genes share a bi-directional promoter which functions weakly in both expressing and non-expression cell types. Recent studies in my laboratory have identified cis-acting regulatory elements which enhance or repress transcription in a cell/tissue specific manner. Current studies are directed at characterizing the cis- and trans- acting factors which regulate the transcription of these genes and understanding the molecular basis for the modulation of collagen IV gene expression by growth factors and cytokines.