Michal Laniado Schwartzman, Ph.D.
Professor and Chair of Pharmacology
Department of Pharmacology
Basic Sciences Building
New York Medical College
Valhalla, NY 10595
Our research consists of two projects focused on the role of lipid autacoids, more specifically cytochrome P450-derived eicosanoids, in the regulation of inflammation and vascular function in the areas of the cardiovascular system and vision.
Ocular surface inflammation and neovascularization.
We have shown that injury to the ocular surface provokes inflammatory and angiogenic response that is mediated by corneal epithelial-derived lipid mediators generated by a cytochrome P450 monooxygnease, identified as CYP4B1. These lipid mediators exhibit potent inflammatory and angiogenic properties. Studies in the lab are directed towards the elucidation of the cellular and molecular mechanisms underlying the inflammatory and angiogenic activity of these metabolites including receptor identification, activation of nuclear factors and induction of gene expression. Work is also being done to identify the anti-inflammatory and cytoprotective pathways that control the action of CYP4B1-derived inflammatory and angiogenic eicosanoids. These studies address the pathophysiological processes involved in corneal neovascularization, a major problem in clinical ophthalmology.
Cytochrome P450 eicosanoids in Hypertension
We have shown a correlation between the production of a renal cytochrome P450 (CYP) arachidonate metabolite, namely, 20-hydroxyeicosatetraenoic acid (20-HETE), and the development of hypertension in experimental animal models and clinical studies. Studies are aimed at understanding 20-HETE cellular and molecular mechanisms of action with the goal of uncovering novel therapeutic targets for the treatment of hypertension driven by increased androgen levels that not only occur in men but is also believed to underlie the increased susceptibility to hypertension in menopausal women. The experimental approach is multi-faceted and includes the use of transgenic mice and genetically modified rats as well as molecular and pharmacological probes together with cell culture models.
Post Graduate Studies
Graduate Degree: M.S., Ph.D.
Graduate Degree Institution: Tel-Aviv University (Israel)
Schwartzman ML, Iserovich P, Gotlinger K, Bellner L, Dunn MW, Sartore M, Grazia Pertile M, Leonardi A, Sathe S, Beaton A, Trieu L, and Sack R. Profile of lipid and protein autacoids in diabetic vitreous correlates with the progression of diabetic retinopathy. Diabetes 59: 1780-1788, 2010.
Inoue K, Sodhi K, Puri N, Gotlinger KH, Cao J, Rezzani R, Falck JR, Abraham NG, and Laniado-Schwartzman M. Endothelial-specific CYP4A2 overexpression leads to renal injury and hypertension via increased production of 20-HETE. Am J Physiol Renal Physiol 297: F875-884, 2009.
Cheng J, Ou JS, Singh H, Falck JR, Narsimhaswamy D, Pritchard KA, Jr., et al. 20-Hydroxyeicosatetraenoic acid causes endothelial dysfunction via eNOS uncoupling. Am J Physiol Heart Circ Physiol. 2008 Feb;294(2):H1018-26.
Singh H, Cheng J, Deng H, Kemp R, Ishizuka T, Nasjletti A, Laniado Schwartzman M. Vascular CYP4A expression and 20-HETE synthesis contributes to endothelial dysfunction in androgen-induced hypertension. Hypertension 50:123-129, 2007. Commentary by Roman & Lombard, Hypertension, 50:37-38, 2007.
Seta F, Bellner L, Colombrita C, Mezentsev A, Kemp R, Dunn MW, Gronert K, Abraham NG and Laniado-Schwartzman M. Heme oxygenase-2 (HO-2) knockout mice display impaired corneal wound healing and marked neovascularization. Am. J. Pathol. 169:1612-1623, 2006.
Wang JS, Singh H, Zhang F, Ishizuka T, Deng H, Kemp R, Wolin MS, Hintze TH, Abraham NG, Nasjletti A, Laniado-Schwartzman M: Endothelial dysfunction and hypertension in rats transduced with CYP4A2 adenovirus, Circ Res, 98:962-969, 2006. Commentary in Circ Res 2006 98:866-7.
Jiang M, Mezentsev A, Byun K, Falck JR, Miano JM, Abraham NG, Laniado-Schwartzman M. Smooth Muscle-Specific Expression of CYP4A1 Induces Endothelial Sprouting in Renal Arterial Microvessels. Circ Res. 94(2):167-74, 2004. Cover page.
Mastyugin V, Zhang WX, Ashkar S, Dunn MW and Laniado-Schwartzman M. Promoter activity and regulation of the corneal CYP4B1 gene by hypoxia. J Cell Biochem. 91(6):1218-38, 2004.
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