Barbara J. Clark, Ph.D.

Associate Professor

Department of Biochemistry and Molecular Biology


319 Abraham Flexner Way, HSC-A, Room 501 502-852-2814 502-852-6222 (fax) bjclar01@louisville.edu

Education

PhD, 1992, University of Texas Southwestern Medical Center, Dallas, TX

Research Interest

Regulation and Function of the START family of Lipid/Sterol Transporters.

Laboratory Personnel

Renate Meier

Research Interests

  1. 1)  START Family of Cholesterol Transporters in Disease. We are interested in defining the role of STARD5 in cholesterol metabolism and trafficking in polarized epithelial cells. Our studies focus on renal proximal tubules and determining the mechanisms regulating the expression and function of STARD5 in normal kidney and in diabetes-induced nephrophathy. This work is in collaboration with Drs. Paul Epstein (Pediatrics) and Eleanor Lederer (Nephrology) at the University of Louisville. A second interest is determining whether the START proteins contribute to development of chemotherapeutic resistance in cancer. Currently we are investigating the role of STARD5 in lung adenocarcinoma resistance. This work is in collaboration with Dr. Carolyn M. Klinge (Biochemistry).
  2. 2)  Steroid hormone biosynthesis regulation by transcriptional control of the steroidogenic acute regulatory protein (StAR). [Detailed Description with Diagrams]
  3. 3)  Arsenic and Male Reproductive Development and Function - Proper development of the urogenital tract requires specific stage-dependent expression of gene networks in utero as well as in early postnatal life to establish adult reproductive functions. Thus, both fetal developmental stages and puberty represent particularly susceptible windows for endocrine disruption. Our lab has initiated studies to test prenatal arsenic exposures on adult male reproductive function. Using CD-1 mice, we have shown that arsenite exposure leads to suppressed serum testosterone levels in adult male mice only after puberty. Our goal is to establish testis gene networks to model the developmental stage and target specific alterations as a result of in utero arsenite exposure. We will test the hypothesis that prenatal As exposure disrupts epigenetic programming required for proper fetal or adult Leydig cell development. This work is a collaborative effort with Drs. Cynthia Corbitt (Biology), Carolyn Klinge (Biochemistry & Molecular Biology), Zhenmin Lei (Medicine-Ob-Gyn), and J. Christopher States (Pharmacology & Toxicology) and at the University of Louisville.

Selected Publications

Chen YC, Meier RK, Zheng S, Khundmiri SJ, Tseng MT, Lederer ED, Epstein PN, Clark BJ. (2009)  Steroidogenic Acute Regulatory (StAR)-Related lipid Transfer Domain Protein 5 (STARD5) Localization and Regulation in Renal Tubules.  Am J Physiol Renal Physiol. 2009 May 27. [Epub ahead of print] PMID: 19474188 [PubMed - as supplied by publisher]

Clark B.J. and Cochrum R.K. (2007). The Steroidogenic Acute Regulatory Protein as a Target of Endocrine Disruption in Male Reproduction.  Drug Metabolism Reviews 39(2-3):353-70.

Y.C. Chen, R.K. Cochrum, M.T. Tseng, D.T. Ghooray, J.P. Moore, S.J. Winters, and B.J. Clark 2007. Effects of CDB-4022 on Leydig Cell Function in Adult Male Rats.  Biol. Reprod. 77, 1017-1026.

Clem B.F., and Clark B.J. (2006). Association of the mSin3A-histone deacetylase 1/2 corepressor complex with the mouse steroidogenic acute regulatory protein gene. Mol Endocrinol 20, 100-113.

Clem B.F., Hudson E.A., and Clark B.J. (2005). Cyclic adenosine 3',5'-monophosphate (cAMP) enhances cAMP-responsive element binding (CREB) protein phosphorylation and phospho-CREB interaction with the mouse steroidogenic acute regulatory protein gene promoter. Endocrinology 146, 1348-1356.

Clark B.J., and Li J. (2004). Janus kinase 2 signaling in the angiotensin II-dependent activation of StAR expression. Endocr Res 30, 685-693.

Qazzaz H.M., Cao Z., Bolanowski D.D., Clark B.J., and Valdes R., Jr. (2004). De novo biosynthesis and radiolabeling of mammalian digitalis-like factors. Clin Chem 50, 612-620.

Winters S.J., and Clark B.J. (2003). Testosterone synthesis, transport and metabolism. In Contemporary Endocrinology:  Androgens in Health and Disease, C. Bagatell, and W. J. Bremmer, eds. (Totowa, N.J., Humana Press, Inc.), pp. 3-22.

Li J., Feltzer R.E., Dawson K.L., Hudson E.A., and Clark B.J. (2003). Janus kinase 2 and calcium are required for angiotensin II-dependent activation of steroidogenic acute regulatory protein transcription in H295R human adrenocortical cells. J Biol Chem 278, 52355-52362.

el-Masri M.A., Clark B.J., Qazzaz H.M., and Valdes R., Jr. (2002). Human adrenal cells in culture produce both ouabain-like and dihydroouabain-like factors. Clin Chem 48, 1720-1730.

Clark B.J., Ranganathan V., and Combs R. (2001). Steroidogenic acute regulatory protein expression is dependent upon post-translational effects of cAMP-dependent protein kinase A. Mol Cell Endocrinol 173, 183-192.

Mandal P.K., McDaniel L.R., Prough R.A., and Clark B.J. (2001). 7,12-Dimethylbenz[a]anthracene inhibition of steroid production in MA-10 mouse Leydig tumor cells is not directly linked to induction of CYP1B1. Toxicol Appl Pharmacol 175, 200-208.

Wooton-Kee C.R., and Clark B.J. (2000). Steroidogenic factor-1 influences protein-deoxyribonucleic acid interactions within the cyclic adenosine 3,5-monophosphate-responsive regions of the murine steroidogenic acute regulatory protein gene. Endocrinology 141, 1345-1355.