NYMC > Faculty > Directory > By School > School of Medicine(SOM)/Graduate School BMS(GSBMS) > Pharmacology > Schwartzman, Michal

Michal Laniado Schwartzman, Ph.D.

Professor and Chair of Pharmacology

E-mail:  michal_schwartzman@nymc.edu

Phone: (914) 594-4153/3116

Address:
Department of Pharmacology
Basic Science Building, Rm. 514
15 Dana Road
Valhalla, NY  10595

Professional Interests:

Our research consists of two projects focused on the role of lipid autacoids, more specifically cytochrome P450 (CYP)-derived eicosanoids, in the regulation of inflammation and vascular function in the areas of the cardiovascular system and vision.

Ocular Surface Inflammation and Wound Healing:

This project focuses on cellular and molecular mechanisms regulating inflammation, neovascularization and wound healing of the ocular surface. We have identified a novel inflammatory CYP gene expressed in the corneal epithelium of rodents and humans, which is induced in response to hypoxic, chemical and physical injury and mediates the inflammatory and neovascular response to injury via the production of inflammatory eicosanoids and studies are directed towards understanding the importance of this CYP gene in ocular surface pathophysiology by using genetic and pharmacological manipulations (gene transfer, knockout, etc.). In the last few years, this project changed direction prompted by an unexpected observation in mice lacking the heme oxygenase-2 gene. We found that these mice display impaired wound healing and marked corneal neovascularization. This led to a full-fledged investigation of the interplay between the CYP-eicosanoid system and the heme oxygenase system (HO-1 and HO-2), a cytoprotective system that is a key regulator of oxidative stress and inflammatory genes in many tissues, in corneal inflammation/neovascularization and wound healing. 

Cytochrome P450 Eicosanoids in Hypertension:

This project focuses on the role of CYP-derived eicosanoids in the pathogenesis of hypertension and its cardiovascular complications. We have shown a correlation between the production of a renal cytochrome P450 (CYP) arachidonate metabolite, namely, 20-hydroxyeicosatetraenoic acid (20-HETE), and blood pressure in animal models of hypertension. We also showed association between urinary 20-HETE excretion and salt-sensitive hypertension in humans. Recently, we identified 20-HETE as the mediator of androgen-dependent hypertension and a potent endogenous regulator of the angiotensin-converting enzyme (ACE) as well as a key determinant of microvascular dysfunction and remodeling in hypertension. The cellular mechanism underlying the androgen-induced increase in blood pressure and susceptibility to cardiovascular morbidity is not completely known. Studies are aimed at understanding 20-HETE cellular and molecular mechanisms of action with the goal of uncovering novel therapeutic targets (e.g., 20-HETE receptor) for the treatment of cardiovascular complications in hypertension, especially 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 and in conditions such as the polycystic ovary syndrome.  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.

Selected Bibliography:

  1. Garcia V, Joseph G, Shkolnik B, Ding Y, Zhang FF, Gotlinger K, Falck JR, Dakarapu R, Capdevila JH, Bernstein KE and Schwartzman ML. Angiotensin II receptor blockade or deletion of vascular endothelial ACE does not prevent vascular dysfunction and remodeling in 20-HETE-dependent hypertension. Am J Physiol Regul Integr Comp Physiol. 2015;309:R71-8.
  2. Bellner L, Marrazzo G, Van Rooijen N, Dunn MW, Abraham NG, Schwartzman ML. Heme oxygenase-2 deletion impairs macrophage function in wound healing. FASEB J, 2015; 29:105-115.
  3. Wu CC, Gupta T, Garcia V, Ding Y, Schwartzman ML. 20-HETE and blood pressure regulation: Clinical implications. Cardiol Rev. 2014;22:1-12
  4. Wu CC, Mei S, Cheng J, Ding Y, Weidenhammer A, Garcia V, Zhang F, Gotlinger K, Manthati VL, Falck JR, Capdevila JH, Schwartzman ML. Androgen-sensitive hypertension associates with upregulated vascular cyp4a12-20-hete synthase. J Am Soc Nephrol. 2013
  5. Ding Y, Wu CC, Garcia V, Dimitrova I, Weidenhammer A, Joseph G, Zhang F, Manthati VL, Falck JR, Capdevila JH, Laniado Schwartzman M. 20-HETE induces remodeling of renal resistance arteries independent of blood pressure elevation in hypertension. Am J Physiol Renal Physiol. 2013;305:10
  6. Cheng J, Garcia V, Ding Y, Wu CC, Thakar K, Falck JR, Ramu E, Schwartzman ML. Induction of angiotensin-converting enzyme and activation of the renin-angiotensin system contribute to 20-hydroxyeicosatetraenoic acid-mediated endothelial dysfunction. Arterioscler Thromb Vasc Biol. 2012;32:1917-1924
  7. Bellner L, Patil KA, Castellano K, Halilovic A, Dunn MW, Schwartzman ML. Targeted suppression of ho-2 gene expression impairs the innate anti-inflammatory and repair responses of the cornea to injury. Molecular vision. 2011;17:1144-1152
  8. Halilovic A, Patil KA, Bellner L, Marrazzo G, Castellano K, Cullaro G, Dunn MW, Schwartzman ML. Knockdown of heme oxygenase-2 impairs corneal epithelial cell wound healing. Journal of cellular physiology. 2011;226:1732-1740
  9. Schwartzman ML, Iserovich P, Gotlinger K, Bellner L, Dunn MW, Sartore M, Grazia Pertile M, Leonardi A, Sathe S, Beaton A, Trieu L, Sack R. Profile of lipid and protein autacoids in diabetic vitreous correlates with the progression of diabetic retinopathy. Diabetes. 2010;59:1780-1788
  10. Sodhi K, Wu CC, Cheng J, Gotlinger K, Inoue K, Goli M, Falck JR, Abraham NG, Schwartzman ML. Cyp4a2-induced hypertension is 20-hydroxyeicosatetraenoic acid- and angiotensin ii-dependent. Hypertension. 2010;56:871-878
  11. Laffer CL, Gainer JV, Waterman MR, Capdevila JH, Laniado-Schwartzman M, Nasjletti A, Brown NJ, Elijovich F. The t8590c polymorphism of cyp4a11 and 20-hydroxyeicosatetraenoic acid in essential hypertension. Hypertension. 2008;51:767-772

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