Mark Mclean, PHD

Professor, College Of Medicine Molecular Medicine

Professor, College Of Medicine Obstetrics & Gynecology

College Of Medicine Obstetrics & Gynecology

Professor, Ob/Gyn, Medicine, University of South Florida

Academic Email: mmclean@health.usf.edu

Academic Phone: (813) 974-2875

Education

  • PHD, Physiology, University Of Illinois, 1986
  • MS, Cell Biology, Nortern Illinois University, 1981
  • BS, Biology, Northern Illinois University, 1979

Interdisciplinary and Emerging Signature Programs

  • Cardiovascular

Research Interests

  • High density lipoprotein (HDL) plasma levels play a critical role in the pathogenesis of cardiovascular diseases (CVD). HDL is suggested to have protective effects and its reduced level is a major risk factor for CVD. One important aspect of HDL plasma level regulation is “reverse cholesterol (C) transport,” in which HDL particles transport excess C from the arterial wall to the liver for bile acid disposal. C conversion to bile acid in the liver represents a major route for C elimination. The mediator of this process is the HDL-receptor (HDL-R), or scavenger receptor class B (SR-B). In the liver, SR-B type I (SR-BI) mediates selective C uptake from HDL, but the underlying mechanism is still under investigation. In this regard, the SR-B gene was found to have alternatively spliced forms, mainly SR-BI and SR-BII, however, few studies have examined the physiological functions of SR-BI/SR-BII, even though data suggest that SR-BI and SR-BII have different roles in C metabolism. Our laboratory has demonstrated that the expression of SR-BI/SR-BII is controlled by estrogen. The goal of this proposal is to establish the molecular mechanisms of estrogen regulated SR-B alternative splicing (PI3K-Akt pathway and Clk2 kinase) and determine a putative function for SR-BII since this isoform is the least understood and possibly the most critically important HDL-R regulating intracellular C trafficking for bile production. The classical bile acid pathway involves conversion of C via the rate limiting microsomal enzyme, 7alpha-hydroxylase (CYP7A1). In addition to this pathway, bile is also produced by an alternative pathway which utilizes a mitochondrial enzyme, 27-hydroxylase (CYP27A). C transport to the CYP27A appears to be the rate determining step in this pathway and C transport to the CYP27A located on the inner mitochondrial membrane is facilitated by StAR (steroidogenic acute regulatory protein). Since hepatic StAR expression is extremely limited, C transport to the mitochondria is critical and in this proposal we hypothesize that SR-BII may function in this regard. It is important to note that increased 27OH-cholesterol (a product of the CYP27A) levels elicit a reduction in de novo C synthesis via HMG-CoA reductase and enhance LDL-R mRNA expression facilitating greater C uptake. This further supports C transport (possibly mediated by SR-BII & StAR) to the alternative bile acid pathway as a target for the management of hypercholesterolemia.

Memberships

  • American Heart Association (Member, 2011 - Present)
  • American Physiology Society (Member, 1990 - Present)
  • Endocrine Society (Member, 1985 - Present)
  • Society for the Study of Reproduction (Membere, 1981 - Present)

Recent Publications

  • Huang, J, Okuka, M, Lu, W, Tsibris, JC, McLean, MP, Keefe, DL, Liu, L Telomere shortening and DNA damage of embryonic stem cells induced by cigarette smoke Reprod Toxicol. 35: 89-95, 2013.
  • Huang, J.Okuka, M.McLean, M.Keefe, DL.Liu, L. Telomere susceptibility to cigarette smoke-induced oxidative damage and chromosomal instability of mouse embryos in vitro. Free radical biology & medicine. 48(12) : 1663-76, 2010. http://www.ncbi.nlm.nih.gov/pubmed/20381605
  • Huang, J.Okuka, M.McLean, M.Keefe, DL.Liu, L. Effects of cigarette smoke on fertilization and embryo development in vivo. Fertility and sterility. 92(4) : 1456-65, 2009. http://www.ncbi.nlm.nih.gov/pubmed/19019360
  • Lopez, D.Niesen, M.Bedi, M.McLean, MP. Lauric acid dependent enhancement in hepatic SCPx protein requires an insulin deficient environment. Prostaglandins, leukotrienes, and essential fatty acids. 78(2) : 131-5, 2008. http://www.ncbi.nlm.nih.gov/pubmed/18187312
  • Zhang, X.Moor, AN.Merkler, KA.Liu, Q.McLean, MP. Regulation of alternative splicing of liver scavenger receptor class B gene by estrogen and the involved regulatory splicing factors. Endocrinology. 148(11) : 5295-304, 2007. http://www.ncbi.nlm.nih.gov/pubmed/17673517
  • Liu, Q.Merkler, KA.Zhang, X.McLean, MP. Prostaglandin F2alpha suppresses rat steroidogenic acute regulatory protein expression via induction of Yin Yang 1 protein and recruitment of histone deacetylase 1 protein. Endocrinology. 148(11) : 5209-19, 2007. http://www.ncbi.nlm.nih.gov/pubmed/17702849

Awards/Honors

  • Robert J Boucek Award (American Heart Association - 2001)
  • Robert J Boucek Award (American Heart Association, Florida - 1993)
  • Society for Gynecologic Investigation President Award (Society for Gynecologic Investigation - 1992)
  • Endocrine Society New Investigator Award (Endocrine Society - 1989)
  • Serono Young Investigator Award (Serono - 1989)