Ph.D (Biochemistry): University of Calcutta
Post Doc: Harvard Medical School and Dana Farber Cancer Institute
General field of research:
Affiliations other than medicine:
Evans Center for Interdisciplinary Biomedical Research
Whitaker Cardiovascular Institute
715 Albany Street, W507
Phone: (617) 638 4260
Phone: (617) 638 4260
Fax: (617) 638 4066
Research group information
Muhammad Rizvi: Research Associate email@example.com firstname.lastname@example.org
Platelets; Endothelial Cells; Monocytes; CD40L; CD40; Thrombosis
Summary of research interest:
Role of CD40-CD40L and hypoxia in thrombosis and inflammation CD40-CD40L interactions have recently been implicated in atherosclerosis and acute coronary syndromes. Our previous studies showed that recombinant soluble CD40 ligand (rsCD40L) induces ROS formation in isolated platelets, neutrophils, and endothelial cells and enhance endothelial inflammation by increasing the synthesis of CD40L and MCP1 (monocyte chemotactic protein 1) in a redox-sensitive manner. Hypoxia is known to be a pro-angiogenic agent and existence of hypoxia has been recently demonstrated in human advanced atherosclerotic lesions. In a recent study with endothelial and monocytic cells (THP1s), we have reported that hypoxia enhances CD40-CD40L-mediated ROS generation; upregulates synthesis of auto-inflammatory CD40L and ICAM1 (intercellular adhesion molecule 1); enhances HSP27 (heat shock protein 27) phosphorylation and NFkB activation and endothelial-monocyte adehsions. Recently, chronic hypoxia was shown to accelerate the progression of atherosclerosis in ap oE knockout mice. However, the role of hypoxia in the CD40-CD40L mediated progression of atherosclerosis is unknown. We will therefore evaluate the mechanism whereby hypoxia induces CD40-CD40L-mediated autoinflammatory CD40L synthesis and ROS generation in vascular cells present in atherosclerotic regions and also assess the role of hypoxia in the CD40L-mediated thrombosis and platelet-leukocyte-endothelial adhesions responsible for atherosclerotic development.
Chakrabarti S., Vitseva O., Iyu D., Varghese S., and Freedman JE. 2005. The Effect of Dipyridamole on Vascular Cell-Derived Reactive Oxygen Species. J. Pharmacol. Exp. Therap. 15(2):494-500.
Chakrabarti S.*, Varghese S., Vitseva O., Tanriverdi K., Freedman J. 2005. CD40 Ligand Influences Platelet Release of Reactive Oxygen Intermediates. Arterioscler Thromb Vasc Biol. 25(11):2428-34.
Chakrabarti S.*, Blair P, Wu C and Freedman JE. 2007. Redox State of Dipyridamole is a Critical Determinant for its Beneficial Antioxidant and Anti-inflammatory Effects. J. Cardiovasc. Pharmacol. 50(4):449-457.
Chakrabarti S.*, Blair P. and Freedman JE. 2007. CD40-40L Signaling in Vascular Inflammation. J. Biol. Chem. 282(25):18307-18317.
Vanichakarn P., Blair P., Wu C., Freedman JE. and Chakrabarti S.* 2008. Neutrophil CD40 enhances Platelet-mediated inflammation. Thromb. Res. 122(3):346-58.
Rizvi M., Pathak D., Freedman JE. and Chakrabarti S.* 2008. The Role of CD40-CD40L in
Oxidative Stress, Inflammation, and Thrombosis. Trends in Mol. Med. 14(12):530-538.
Chakrabarti S.*, Rizvi M., Pathak D., Kirber MT., and Freedman JE. 2009. Hypoxia influences CD40-CD40L mediated inflammation in endothelial and monocytic cells.Immunol. Lett. 122:170-184.
Chakrabarti S*, Beaulieu L M, Reyelt LA, Iafrati MD, and Freedman JE. 2009. M118, A Novel Low-molecular Weight Heparin with Decreased Polydispersity Leads to Enhanced anticoagulant Activity and Thrombotic Occlusion in ApoE Knockout Mice. J Thromb Thrombolysis (In Press).
Technologies available for sharing upon request:
Fluorescence based localization of NFkappaB in endothelial and monocytic cells
Laser Photochemical Arterial Thrombosis in Mice