Avadhesh C. Sharma, PharmD, PhD Associate Professor Department of Biomedical Sciences The Texas A&M University System Health Science Center Baylor College of Dentistry, 3302 Gaston Avenue Dallas, TX 75246 Office: Rm # 409; Laboratory: Rm # 412. Phone: (214) 828-8303; Fax: (214) 828-8951 ACSharma@bcd.tamhsc.edu Sepsis-induced Myocardial Dysfunction, In vivo and In vitro Paradigms, Apoptosis and Signaling Cascade

Preclinical Research

• Development of Clinical Marker(s) for Early Stages of Congestive Heart Failure in Sepsis and Septic Shock
• Mechanisms of Neutrophil Apoptosis in Septic Patients
• Preclinical development of Hemoglobin-based Blood Substitutes (DCLHB)
• Pharmacological Mechanisms for the Regional Vascular Effect of DCLHB

Cardiovascular Physiology And Pharmacology

• Diabetes, Infection-induced Systemic Inflammatory Response Syndrome, Sepsis, Endotoxemia, Hemorrhage and Ischemia Reperfusion Injury
• Mitogen activated protein kinase Signaling Mechanisms following Endothelin, Matrix metalloproteinase(s), Nitric Oxide Synthase Activation and Free radical Mechanisms

:: Research Experience

::Technical Expertise

Molecular and Biochemical in vitro Methods

• Genomic and Proteomics (Microarray Technique)
  Gene and protein expression of signaling molecules in isolated adult rat ventricular myocytes during sepsis
• Small interference RNA Technique
  Delineate signaling pathway, intrinsic and extrinsic apoptosis in cardiomyocyte
• Protein Isolation and Characterization
  Electrophoresis, immunoblot analysis, Radioimmunoassay and ELISA procedures
• Confocal Microscopy and Imaging
  Caspase-3 fluorescence imaging
• Primary Cell cultures
  Rat Leydig cells, cardiac myocytes, etc.

Whole animal in vivo Methods

• Stereotaxic microsurgery
• Radioactive microsphere technique
• Regional Rheological Studies
• Hemodynamic and cardiodynamic measurements:
• EKG and EEG measurements using BioPac data acquisition system

Development of whole animal models

• Rat and mouse* model

• Hemorrhagic shock
• Systemic Inflammatory response syndrome (Resuscitated and non-resuscitated models)
• Acute brain injury
• Polymicrobial sepsis-induced heart failure in rat and mouse*

• Other animal models:

• Dogs and rabbits

:: Education

:: Career History

:: Teaching Responsibilities

:: Grants and Funding

• Sharma A.C., Sponsor, (Sachin Brahmbhatt, Predoctoral award), (1/1/2005-12/31/2006) Signaling mechanisms in sepsis-induced myocardial dysfunction. Predoctoral fellowship, American Heart Association Northland Affiliate, 07/01/04-6/31/06. (Funded)
• Sharma A.C., Principal Investigator (Oct 2004-05) Determine the efficacy of intervention(s) on hemorrhagic shock-induced cardiovascular Alteration and Mortality. Diffusion Pharmaceutical Inc., (Funded)
• Sharma A.C., Principal Investigator (March 2003-04) Signal transduction mechanisms in estradiol-induced vascular function in female rats, ND EPSCOR IIP Seed Grant, 07/01/03-06/30/04; (Funded).
• Sharma A.C., Principal Investigator (July 2003-06) Endothelin mechanisms in sepsis induced myocardial dysfunction. Academic Research Enhancement Award, NHLBI #66016; (Funded).
• Sharma A.C., Principal Investigator (August 2002-04) “Interactive Endothelin and Nitric Oxide Mechanisms in Myocardial Dysfunction in Sepsis.” Beginning Grant in Aid, Northland Affiliate, American Heart Association, ($39,556; Funded).
• Sharma A.C., Principal Investigator (August 2001) “Interactive Endothelin and Nitric Oxide Mechanisms in Myocardial Dysfunction in Sepsis.” Beginning Grant in Aid, Northland Affiliate, American Heart Association, (Funded)
• Sharma A.C., Principal Investigator (December 2000) Endothelin and Nitric Oxide Mechanisms in Myocardial Dysfunction during endotoxemia.” NDSP North Dakota State University Research Foundation (Funded).
• Sharma A.C., Principal Investigator (February, 2000) Homeostatic Interplay between Endothelin and Nitric Oxide System(s) in Sepsis.” Senior Fellowship, American Heart Association of Metropolitan Chicago, IL ($ 27,500; Funded).
• Sharma A. C., Sponsor, Akanksha Gupta (November 1999-March 2004) Presidential Fellowship, North Dakota State University (Funded).

:: Recent Publications

I. Dissertations:

• Ph D: Studies on Neurotransmitter and Receptor Mechanisms in Learning and Memory and Related Behaviours: Influence of Centrally Acting Drugs
• M Pharmacy: Role of Oxygen Free Radicals in Calcium Paradox and Ischaemia Reperfusion Injury

 II.a Book Chapters :

• Role of Endothelin in Regional Vascular System: Avadhesh C. Sharma and Anil Gulati in Endothelin: Role in Health and Disease, edited by A. Gulati. Harwood Academic Publishers gmbh, Amsterdam, The Netherlands, 1995: 215-232.
• Biological Activities of Endothelin and Their Clinical Significance: Govind Singh, Avadhesh C. Sharma, Sam Rebello and Anil Gulati in Endothelin: Role in Health and Disease, edited by A. Gulati. Harwood Academic Publishers gmbh, Amsterdam, The Netherlands, 1995: 99-116.

II.b Refereed Journal Articles:

Selected Publications

• Chopra M., and Sharma A.C. (2006). Celular and molecular dynamics during sepsis and septic shock-induced myocardial dysfunction. Frontiers of Bioscience, (Under Preparation).
• Sharma A.C. (2006) Sepsis-induced myocardial dysfunction. Shock. (Submitted).
• Gupta A., Kapoor R., Brahmbhatt S., Loken L. and Sharma A.C. (2005). Regulation of myocardial signaling mechanisms following sepsis. Frontiers in Bioscience, Encyclopedia of Bioscience, (Accepted).
• Gupta A.,Aberle N., Kapoor R., Ren J. and Sharma A.C. (2005). BigET-1 induced contractile function is mediated via p38-MAPK phosphorylation in adult rat ventricular myocytes during sepsis. Biochimica et Biophysica Acta (Accepted).
• Chen H., Brahmbhatt S., Gupta A. and Sharma A.C. (2005).Duration of Streptozotocin-Induced Diabetes differentially affects p38-MAPK Phosphorylation in Renal and Vascular Dysfunction. Cardiovascular Diabetology 4: 3 [Article URL: http://www.cardiab.com/content/4/1/3].
• Gupta A.,Aberle N., Ren J. and Sharma A.C. (2005). Endothelin-converting enzyme –1-mediated signaling in adult rat ventricular myocyte contractile function and apoptosis during polymicrobial sepsis. J Mole. Cell Cardiol 38:527-537.
• Brahmbhatt S., Gupta A. and Sharma A.C. (2005) Bigendothelin-1 (1-21) fragment during Early Sepsis Modulates tau, p38-MAPK phosphorylation and Nitric Oxide Synthase Activation. Mole. Cel. Biochem. (In Press).
• Gupta A,Brahmbhatt Sand Sharma AC (2004). Left ventricular mitogen activated protein kinase signaling following polymicrobial sepsis during streptozotocin-induced hyperglycemia. Biochimica et Biophysica Acta 1690:42-53.
• Gupta A and Sharma AC (2004). Despite minimal hemodynamic alterations endotoxemia modulates NOS and p38-MAPK phosphorylation via Metalloendopeptidases. Mol Cell Biochem 265: 47-65.
• Folden DV, Gupta A, Sharma AC, Li S, Saari TJ and Ren J. (2003). Malondialdehyde inhibits cardiac contractile function in ventricular myocytes via a p38 mitogen activated protein kinase-dependent mechanism. British J. Pharmacol. 39: 1310-1316.
• Gupta A. and Sharma A.C. (2003). Metalloendopeptidase Inhibition Regulates Phosphorylation of p38-mitogen Activated Protein Kinase and Nitric Oxide Synthase in Heart after Endotoxemia. Shock 20: 375-381.
• Ren J., Ren B.H. and Sharma A.C. (2002). Sepsis-induced depressed contractile function of isolated ventricular myocytes is due to altered calcium transient properties. Shock 18: 285-288.
• Sharma A.C., Singh G. and Gulati A. (2002). Decompensation Characterized by Decreased Vascular Perfusion to the Heart and Brain in Hypotensive Shock: Role of Endothelin-1. J. Trauma 53: 531-536.
• Omachi, A., Sharma A.C., Alden K.J., Sam II A.D., Alden K.J., and Ferguson J.L. (2002) Induction of peritoneal sepsis increases the susceptibility of isolated hearts to a calcium paradox-mediated injury. Shock 17:193-198.
• Sam II A.D., Sharma A.C., Rice A.N., Ferguson J.L. and Law W.R. (2000) Interdependence of adenosine and nitric oxide in hepato-splanchnic circulation during sepsis. J. Surg. Res. 94: 61-67.
• Sharma A.C., Fogelson B.G., Nawas S.I., Sam II A.D., Alden K.J., Vigneswaran W.T., Ferguson J.L. and Law W.R. (1999) Increased endothelin-1 but not nitric oxide concentration following myocardial reperfusion in diabetics undergoing Coronary artery bypass grafting. Ann. Thoracic Surgery 67: 1659-1663.
• Fogelson B.G., Nawas S.I., Vigneswaran W.T., Ferguson J.L., Law W.R. and Sharma A.C. (1998) Diabetic patients produce an increase in coronary sinus endothelin-1 after coronary artery bypass grafting. Diabetes 47: 1161-1163.
• Sharma A.C., Sam II A.D., Lee L.Y., Hales D.B., Law WR, Ferguson J.L. and Bosmann H.B. (1998) Effect of N G-nitro-L-arginine methyl ester on testicular blood flow and serum steroid hormones during sepsis. Shock 9: 416-421.
• Gulati A., Sen A. P., Sharma A. C. and Singh, G. (1997) Role of endothelin and nitric oxide mechanisms in the resuscitative effects of diaspirin crosslinked hemoglobin, a hemoglobin based blood substitute following hemorrhage in the rat. Am. J. Physiol. (Heart Circ. Physiol. 42) 273: H827-H836.
• Sharma A. C., Motew S. J., Farias S., Alden K. J., Bosmann H.B., Law W.R. and Ferguson J. L. (1997) Sepsis alters myocardial and plasma concentrations of endothelin and nitric oxide in rats. J. Mol. Cell. Cardiol. 29: 1469-1477.
• Sharma A. C., Bosmann H.B., Motew S. J., Hales K.H., Hales D.B. and Ferguson J. L. (1996) Steroid hormone alterations following induction of chronic intraperitoneal sepsis in male rats. Shock 6: 150-154.
• Sharma A. C., Singh G. and Gulati A. (1995) Role of NO mechanism in the cardiovascular effects of diaspirin cross-linked hemoglobin in anesthetized rats. Am. J. Physiol. (Heart Circ. Physiol.) 269: H1379-H1388.
• Sharma A. C. and Gulati A. (1995) Yohimbine modulates diaspirin cross-linked hemoglobin-induced systemic hemodynamic and regional circulatory effects. Crit. Care Med. 23: 874-884.