Thomas Kelley, Ph.D.
BRB Room 833
(216) 368 0831 Phone
(216) 368 4223 Fax
Tom Kelley received his B.A. from the College of Wooster in 1988. He attended the University of Notre Dame where he was awarded his Ph.D. in Biochemistry in 1993. Dr. Kelley came to Case in 1993 where he worked as a Postdoc.
- Identifying a mechanistic link between the loss of CFTR function and altered cell-signaling control in CF airway epithelial cells – It is unclear how a loss of CFTR function influences signal transduction cascades. As described above, the GTPases seem to be a common link between two of these signaling abnormalities. We have identified increased expression of the GTPase RhoA in CF epithelial cells and are interested in exploring the GTPase regulatory pathways in order to explain these signaling phenomenon in CF. Our current focus is an examination of the isoprenoid/cholesterol synthesis pathway. Many CF-related characteristics can be explained by an increase in isoprenoid synthesis and there is an association between cholesterol regulation and the ATP binding cassette (ABC) proteins, a class of proteins that includes the CFTR. The immediate goal of this project is to characterize the regulation of the isoprenoid/cholesterol synthesis pathway in CF epithelial cells in order to identify the mechanism by which CFTR function influences cell signaling cascades.
- Determining cell signaling consequences of impaired intracellular cholesterol transport - These studies focus primarily on elucidating the consequences of lost NPC1 function in Niemann-Pick type C disease, a pediatric neurological disorder. This project is related to our CF studies as it appears that similar signaling alterations are taking place in affected cell types of both diseases. We have identified impaired induction of NOS2 expression and elevated RhoA expression in NPC models that are directly mediated by lesions in cholesterol processing pathways. These studies are also applicable to understanding related processes in atherosclerotic disease.
Jiang D, Fang D, Kelley TJ, Burgess JD.
"Electrochemical analysis of cell plasma membrane cholesterol at the airway surface of mouse trachea."
Anal Chem. 2008 Feb 15;80(4):1235-9.
Jiang D, Devadoss A, Palencsár MS, Fang D, White NM, Kelley TJ, Smith JD, Burgess JD.
"Direct electrochemical evaluation of plasma membrane cholesterol in live mammalian cells."
J Am Chem Soc. 2007 Sep 19;129(37):11352-3.
Corey DA, Kelley TJ.
"Elevated small GTPase activation influences the cell proliferation signaling control in Niemann-Pick type C fibroblasts."
Biochim Biophys Acta. 2007 Jul;1772(7):748-54.
Ross KR, Corey DA, Dunn JM, Kelley TJ.
"SMAD3 expression is regulated by mitogen-activated protein kinase kinase-1 in epithelial and smooth muscle cells."
Cell Signal. 2007 May;19(5):923-31.
White NM, Jiang D, Burgess JD, Bederman IR, Previs SF, Kelley TJ.
"Altered cholesterol homeostasis in cultured and in vivo models of cystic fibrosis."
Am J Physiol Lung Cell Mol Physiol. 2007 Feb;292(2):L476-86.
White NM, Corey DA, Kelley TJ
"Mechanistic Similarities between Cultured Cell Models of Cystic Fibrosis & Niemann-Pick Type C"
Am J Respir Cell Mol Biol. 2004 Nov;31(5):538-43
Lee JY, Elmer HL, Ross KR, Kelley TJ
"Isoprenoid-mediated control of SMAD3 expression in a cultured model of cystic fibrosis epithelial cells"
Am J Respir Cell Mol Biol. 2004 Aug;31(2):234-40
Kreiselmeier NE, Kraynack NC, Corey DA, Kelley TJ
"Statin-mediated correction of STAT1 signaling and inducible nitric oxide synthase expression in cystic fibrosis epithelial cells"
Am J Physiol Lung Cell Mol Physiol. 2003 Dec;285(6):L1286-95
Kraynack NC, Corey DA, Elmer HL, Kelley TJ
"Mechanisms of NOS2 regulation by Rho GTPase signaling in airway epithelial cells"
Am J Physiol Lung Cell Mol Physiol. 2002 Sep;283(3):L604-11
Ziady AG, Kelley TJ, Milliken E, Ferkol T, Davis PB
"Functional evidence of CFTR gene transfer in nasal epithelium of cystic fibrosis mice in vivo following luminal application of DNA complexes targeted to the serpin-enzyme complex receptor"
Molecular Therapy 5(4):413-9, 2002