Dr. Killen's research interests include basement membranes, which are specialized extracellular matrices that 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 Dr. Killen’s 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.
Link to PubMed Citations
Monrad SU, Killen PD, Anderson MR, Bradke A, Kaplan MJ. The role of aldosterone blockade in murine lupus nephritis. Arthritis Res Ther. 2008;10(1):R5. Epub 2008 Jan 15.
Denny MF, Chandaroy P, Killen PD, Caricchio R, Lewis EE, Richardson BC, Lee KD, Gavalchin J, Kaplan MJ. Accelerated macrophage apoptosis induces autoantibody formation and organ damage in systemic lupus erythematosus. J Immunol. 2006 Feb 15;176(4):2095-104.
Nakashima E, Pop-Busui R, Towns R, Thomas TP, Hosaka Y, Nakamura J, Greene DA, Killen PD, Schroeder J, Larkin DD, Ho YL, Stevens MJ. Regulation of the human taurine transporter by oxidative stress in retinal pigment epithelial cells stably transformed to overexpress aldose reductase. Antioxid Redox Signal. 2005 Nov-Dec;7(11-12):1530-42.
Ohkita M, Wang Y, Nguyen ND, Tsai YH, Williams SC, Wiseman RC, Killen PD, Li S, Yanagisawa M, Gariepy CE. Extrarenal ETB plays a significant role in controlling cardiovascular responses to high dietary sodium in rats. Hypertension. 2005 May;45(5):940-6. Epub 2005 Apr 4.