Biodata of Dr Manoj Kumar Barthwal :::: Central Drug Research Institute

Dr. Manoj Kumar Barthwal

Senior Scientist
Division of Pharmacology
CSIR-Central Drug Research Institute
Lucknow-226 031

E-Mail	[email protected]
Educational qualifications	M.Sc (Biochemistry): Lucknow University (1997) PhD (Biochemistry): Lucknow University & CDRI (2001)
Date of Birth	03.05.1973

PROFESSIONAL EXPERIENCE

•	2001-2006: Post Doctoral Research Associate: Cardiovascular Research Institute, Texas A&M University HSC.
•	2006-Present: Scientist, Pharmacology Division, CDRI
•	2010-2011: Visiting Scientist, National Heart, Lung and Blood Institute, NIH, Bethesda, MD, USA

RESEARCH INTEREST

•	Cardiometabolic disorders
•	Atherosclerosis
•	Inflammation and Innate Immunity
	Our research group is interested in understanding the molecular mechanism of cardiometabolic disorders like atherosclerosis and the role of inflammation and hyperlipidemia in the same. We are using animal models and cell based systems for achieving our research goals. Emphasis is on the elucidation of cellular signaling events in inflammatory cells and vessel wall. Protein kinase mediated signaling and phosphorylation events are of special interest. Presently we are focusing on protein kinases that can regulate the innate and adaptive immune response during atherosclerosis progression. Final aim is to identify and develop therapeutic targets for cardiometabolic disorders. Recent Findings Molecular mechanisms of chronic inflammation are novel therapeutic targets for treating disorders like atherosclerosis and rheumatoid arthritis (1). Recently International Atherosclerosis Society published our labs view on this aspect (2). Interleukin 1 Receptor Associated Kinase (IRAK) is an important regulator of innate and adaptive immune response. Our group demonstrated that IRAK regulates IL-1β production in monocytic cells. In this study a novel mechanism of IL-1β production that involves TLR2, CD11b, PKCδ-IRAK1-JNK-AP1 axis was identified. This study proposes new therapeutic targets for the prevention of chronic inflammatory diseases involving IL-1β production (3). How this pathway is important for cardiometabolic disorders is under investigation. A recent study demonstrates role of PI3K in native LDL uptake in MCSF and GMCSF differentiated macrophages (4) Novel anti-atherothrombotic molecules have been characterized in animal models of atherosclerosis developed by the lab (5,6,7). Earlier studies by PI showed negative and positive regulation of MLK3-JNK pathway by AKT (8) and GSK3β (9) respectively and identified ceramide as an agonist of drosophila and mammalian mixed lineage kinase (10, 11). Our collaborative research work demonstrates role of CDK2 nitrosylation (12) and ascorbate (13) in HL-60 cell cycle and sustained neutrophil free radical generation respectively.

TOP 25 PUBLICATIONS

•	Singh A, Singh V, Tiwari RL, Chandra T, Kumar A, Dikshit M, Barthwal MK. The IRAK-ERK-p67phox-Nox-2 axis mediates TLR4, 2-induced ROS production for IL-1β transcription and processing in monocytes. Cell Mol Immunol. 2015 Aug 31. doi: 10.1038/cmi.2015.62. [Epub ahead of print]PMID: 26320741
•	Jain M, Singh A, Singh V, Maurya P, Barthwal MK. Gingerol Inhibits Serum-Induced Vascular Smooth Muscle Cell Proliferation and Injury-Induced Neointimal Hyperplasia by Suppressing p38 MAPK Activation. J Cardiovasc Pharmacol Ther. 2015 Aug 3. pii: 1074248415598003. [Epub ahead of print] PMID: 26240073
•	Jain M, Singh A, Singh V, Barthwal MK.. Involvement of interleukin-1 receptor-associated kinase-1 in vascular smooth muscle cell proliferation and neointimal formation after rat carotid injury. Arterioscler Thromb Vasc Biol. 2015 Jun;35(6):1445-55. doi: 10.1161/ATVBAHA.114.305028. Epub 2015 Apr 23.
•	Dubey M, Singh AK, Awasthi D, Nagarkoti S, Kumar S, Ali W, Chandra T, Kumar V, Barthwal MK, Jagavelu K, Sánchez-Gómez FJ, Lamas S, Dikshit M. L-Plastin S-glutathionylation promotes reduced binding to β-actin and affects neutrophil functions. Free Radic Biol Med. 2015 Sep;86:1-15. doi: 10.1016/j.freeradbiomed.2015.04.008. Epub 2015 Apr 14.
•	Singh V, Rana M, Jain M, Singh N, Naqvi A, Malasoni R, Dwivedi AK, Dikshit M, Barthwal MK. Curcuma oil attenuates accelerated atherosclerosis and macrophage foam-cell formation by modulating genes involved in plaque stability, lipid homeostasis and inflammation. Br J Nutr. 2014 Nov 13:1-14. [Epub ahead of print]
•	Tiwari RL, Singh V, Singh A, Rana M, Verma A, Kothari N, Kohli M, Bogra J, Dikshit M, Barthwal MK. PKCδ-IRAK1 axis regulates oxidized LDL-induced IL-1β production in monocytes. J Lipid Res. 2014 May 2;55(7):1226-1244. [Epub ahead of print]
•	. Khanna V, Jain M, Singh V, Kanshana JS, Prakash P, Barthwal MK, Murthy PS, Dikshit M. Cholesterol diet withdrawal leads to an initial plaque instability and subsequent regression of accelerated iliac artery atherosclerosis in rabbits. PLoS One. 2013 Oct 17;8(10):e77037. doi: 10.1371/journal.pone.0077037. eCollection 2013.
•	Jyoti A, Singh AK, Dubey M, Kumar S, Saluja R, Keshari RS, Verma A, Chandra T, Kumar A, Bajpai VK, Barthwal MK, Dikshit M. Interaction of inducible nitric oxide synthase with rac2 regulates reactive oxygen and nitrogen species generation in the human neutrophil phagosomes: implication in microbial killing. Antioxid Redox Signal. 2014 Jan 20;20(3):417-31. doi: 10.1089/ars.2012.4970. Epub 2013 Sep 17.
•	Singh V, Jain M, Misra A, Khanna V, Rana M, Prakash P, Malasoni R, Dwivedi AK, Dikshit M, Barthwal MK. Curcuma oil ameliorates hyperlipidaemia and associated deleterious effects in golden Syrian hamsters. Br J Nutr. 2013 Aug 28;110(3):437-46. doi: 10.1017/S0007114512005363. Epub 2013 May 15.
•	Barthwal MK, Anzinger JJ, Xu Q, Bohnacker T, Wymann MP, Kruth HS. Fluid-phase pinocytosis of native low density lipoprotein promotes murine M-CSF differentiated macrophage foam cell formation. PLoS One. 2013;8(3):e58054. doi: 10.1371/journal.pone.0058054. Epub 2013 Mar 11. PMID: 23536783 Free PMC Article
•	Keshari RS, Jyoti A, Dubey M, Kothari N, Kohli M, Bogra J, Barthwal MK, Dikshit M. Cytokines induced neutrophil extracellular traps formation: implication for the inflammatory disease condition. PLoS One. 2012;7(10):e48111. doi: 10.1371/journal.pone.0048111. Epub 2012 Oct 26.
•	Anzinger JJ, Chang J, Xu Q, Barthwal MK, Bohnacker T, Wymann MP, Kruth HS. Murine bone marrow-derived macrophages differentiated with GM-CSF become foam cells by PI3Kγ-dependent fluid-phase pinocytosis of native LDL. J Lipid Res. 2012 Jan;53(1):34-42. doi: 10.1194/jlr.M018887. Epub 2011 Nov 4.
•	Tiwari RL, Singh V, Singh A, Barthwal MK. IL-1R-associated kinase-1 mediates protein kinase Cδ-induced IL-1β production in monocytes. J Immunol. 2011 Sep 1;187(5):2632-45. doi: 10.4049/jimmunol.1002526. Epub 2011 Jul 29.
•	Saluja R, Jyoti A, Chatterjee M, Habib S, Verma A, Mitra K, Barthwal MK, Bajpai VK, Dikshit M. Molecular and biochemical characterization of nitric oxide synthase isoforms and their intracellular distribution in human peripheral blood mononuclear cells. Biochim Biophys Acta. 2011 Oct;1813(10):1700-7. doi: 10.1016/j.bbamcr.2011.06.008. Epub 2011 Jun 23.
•	. Prakash P, Khanna V, Singh V, Jyoti A, Jain M, Keshari RS, Barthwal MK, Dikshit M. Atorvastatin protects against ischemia-reperfusion injury in fructose-induced insulin resistant rats. Cardiovasc Drugs Ther. 2011 Aug;25(4):285-97. doi: 10.1007/s10557-011-6312-x.
•	Kumar S, Barthwal MK, Dikshit M. Nitrite-mediated modulation of HL-60 cell cycle and proliferation: involvement of cyclin-dependent kinase 2 activation. J Pharmacol Exp Ther. 2011 Jun;337(3):812-21. doi: 10.1124/jpet.110.177444. Epub 2011 Mar 16.
•	Singh V, Jain M, Prakash P, Misra A, Khanna V, Tiwari RL, Keshari RS, Singh S, Dikshit M, Barthwal MK. A time course study on prothrombotic parameters and their modulation by anti-platelet drugs in hyperlipidemic hamsters. J Physiol Biochem. 2011 Jun;67(2):205-16. doi: 10.1007/s13105-010-0065-z. Epub 2011 Feb 1.
•	Kothari N, Keshari RS, Bogra J, Kohli M, Abbas H, Malik A, Dikshit M, Barthwal MK. Increased myeloperoxidase enzyme activity in plasma is an indicator of inflammation and onset of sepsis. J Crit Care. 2011 Aug;26(4):435.e1-7. doi: 10.1016/j.jcrc.2010.09.001. Epub 2010 Oct 30.
•	Kumar S, Barthwal MK, Dikshit M. Cdk2 nitrosylation and loss of mitochondrial potential mediate NO-dependent biphasic effect on HL-60 cell cycle. Free Radic Biol Med. 2010 Mar 15;48(6):851-61. doi: 10.1016/j.freeradbiomed.2010.01.004. Epub 2010 Jan 15.
•	Singh V, Tiwari RL, Dikshit M, Barthwal MK. Models to study atherosclerosis: a mechanistic insight. Curr Vasc Pharmacol. 2009 Jan;7(1):75-109. Review.
•	Tiwari, RL, Singh V and Barthwal MK. Macrophages: An elusive yet emerging therapeutic target of atherosclerosis. Med Res Rev 2007 Nov 14; 28 (4):483-544 [Epub ahead of print]
•	Barthwal MK, Sathyanarayana P, Kundu CN, Rana B, Pradeep A, Sharma C, Woodgett JR, Rana A. Negative regulation of mixed lineage kinase 3 by protein kinase B/AKT leads to cell survival. J Biol Chem. 2003 Feb 7; 278(6):3897-902. Epub 2002 Nov 27.
•	. Mishra R, Barthwal MK, Sondarva G, Rana B, Wong L, Chatterjee M, Woodgett JR, Rana A. Glycogen synthase kinase-3beta induces neuronal cell death via direct phosphorylation of mixed-lineage K3. J Biol Chem. 2007 Oct 19; 282(42):30393-405. Epub 2007 Aug 21 (*Equal contribution)
•	Sathyanarayana P, Barthwal MK, Lane ME, Acevedo SF, Skoulakis EM, Bergmann A, Rana A. Drosophila mixed lineage kinase/slipper, a missing biochemical link in Drosophila JNK signaling. Biochim Biophys Acta. 2003 Apr 7; 1640(1):77-84.
•	Sathyanarayana P, Barthwal MK, Kundu CN, Lane ME, Bergmann A, Tzivion G, Rana A. Activation of the Drosophila MLK by ceramide reveals TNF-alpha and ceramide as agonists of mammalian MLK3. Mol Cell. 2002 Dec; 10(6):1527-33.

LAB MEMBERS

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PRESENT LAB RESEARCH FELLOWS
1. Minakshi Rana (SRF)
2. Preeti Maurya (SRF)
3. Anant Jaiswal (SRF)
4. Priya Gupta (JRF)
5. Amit Kumar (JRF)
6. Samreen Sadaf (JRF)
7. Heena Agarwal (PA)
8. Santosh Kumar (PA)
PAST Ph.D FELLOWS
1. Vishal Singh
2. Manish Jain
3. Ankita Singh
4. Rajiv Lochan Tiwari