Agrawal

agrawal

Alok Agrawal, Ph.D.
Professor, Department of Biomedical Sciences


Contact Information:

Alok Agrawal, Ph.D.
Professor, Department of Biomedical Sciences
James H Quillen College of Medicine
PO Box 70582
Carl A Jones Hall (VA Bldg 1) Room 164
Phone:  423-439-6336
Email: 

Key Laboratory Personnel:  

Avinash Thirumalai, Graduate Student
Toh B. Gang, Graduate Student
 
 

Education and Professional Background:   

Dr. Agrawal is a professor in the Department of Pharmacology, Quillen College of Medicine, ETSU, in Johnson City, Tennessee.   He received his Ph.D. from Visva Bharati University in India, and post-doctoral training at the University of Alabama at Birmingham. He was a research faculty in the Department of Biochemistry at Case Western Reserve University in Cleveland, before joining ETSU in 2002.     

Research Interests:  

1.   Functions of C-reactive protein in inflammatory diseases

2.   Regulation of C-reactive protein gene expressio

My principal area of research is focused on the structure-function relationships of C-reactive protein (CRP) in inflammation. CRP is primarily a plasma protein, but it is also localized at the sites of inflammation in both humans and experimental animals. To define the functions of CRP in the circulation and at the inflammatory sites, we are currently working on the following three projects:

1. Functions of CRP in pneumococcal infections: In vitro, CRP binds to cell wall C-polysaccharide on Streptococcus pneumoniae and subsequently activates the complement system in serum. In murine models of infection, human CRP is protective against lethal infection with S. pneumoniae. Our long-term goal is to define the mechanisms by which CRP protects against pneumococcal infection in mice. How does CRP, directly or indirectly, act on the bacterial surfaces to kill them? We are testing the hypothesis that the activation and recruitment of the complement components on the pneumococcal surface, subsequent to the binding of CRP to pneumococci, participate in CRP-mediated protection of mice from pneumococcal infection.  

2. Functions of CRP in atherosclerosis: CRP is transported from the circulation to the arterial wall and localizes with modified low-density lipoproteins (LDL) in human atherosclerotic lesions, consistent with its capability of CRP to bind to modified forms of LDL in vitro. Recently, CRP was shown to be functioning as an atheroprotective molecule in a mouse model of human atherosclerosis. The mechanism of action of CRP, however, in the uptake of modified atherogenic LDL by macrophages, in the formation of foam cells, and in the development of atherosclerosis are not known. To define the possible role of CRP-LDL interactions in the pathogenesis of atherosclerosis, we are investigating the role of CRP in the uptake of LDL by human macrophages to form LDL-loaded macrophage foam cells, the sites on CRP required for binding to modified forms of LDL, and the role of CRP in atherosclerotic lesions formed in mouse models of human atherosclerosis.

3. Regulation of CRP gene expression: In response to inflammatory mediators, various transcription factors are activated in the hepatocytes. Our research involves the interactions of the transcription factors with the CRP promoter to regulate CRP expression in human hepatocytes. Cholesterol-lowering drugs, statins, also lower serum CRP levels. The mechanism of action of statins on lowering serum CRP levels is also unclear. Our goal is define the mechanism of regulation of serum CRP levels in normal healthy population and in individuals under statin therapy.

Active Research Funding:  

NIH
5R01HL071233-10 (Agrawal, PI)
Title: Structure-function relationships of C-reactive protein

 

Selected Publications:

  1. Suresh, M. V., S. K. Singh, and A. Agrawal. Interaction of calcium-bound C-reactive protein with fibronectin is controlled by pH: In vivo implications. J. Biol. Chem. 279:52552-52557, 2004.
  2. Voleti, B., and A. Agrawal. Regulation of basal and induced expression of C-reactive protein through an overlapping element for OCT-1 and NF-κB on the proximal promoter. J. Immunol. 175:3386-3390, 2005.
  3. Suresh, M. V., S. K. Singh, D. A. Ferguson Jr., and A. Agrawal. Role of the property of C-reactive protein to activate the classical pathway of complement in protecting mice from Streptococcus pneumoniae infection. J. Immunol. 176:4369-4374, 2006.
  4. Singh, S. K.*, M. V. Suresh*, D. A. Ferguson Jr., and A. Agrawal. Human C-reactive protein protects mice from Streptococcus pneumoniae infection without binding to pneumococcal C-polysaccharide. J. Immunol. 178:1158-1163, 2007.
  5. Singh, P. P., B. Voleti, and A. Agrawal. A novel RBP-Jκ-dependent switch from C/EBPβ to C/EBPζ at the C/EBP-binding site on the C-reactive protein promoter. J. Immunol. 178:7302-7309, 2007.
  6. Singh, S. K., M. V. Suresh, D. C. Prayther, J. P. Moorman, A. E. Rusinol, and A. Agrawal. C-reactive protein-bound enzymatically modified low-density lipoprotein does not transform macrophages into foam cells. J. Immunol. 180:4316-4322, 2008.
  7. Hammond, Jr., D. J.*, S. K. Singh*, J. A. Thompson, B. W. Beeler, A. E. Rusinol, M. K. Pangburn, L. A. Potempa, and A. Agrawal. Identification of acidic pH-dependent ligands of pentameric C-reactive protein. J. Biol. Chem. 285:36235-36244, 2010.
  8. Thirumalai, A.*, B. Voleti*, D. J. Hammond Jr.*, and A. Agrawal. Oct-1 acts as a transcriptional repressor on the C-reactive protein promoter. Mol. Immunol. 52: 242-248, 2012.
  9. Thirumalai, A.*, S. K. Singh*, D. J. Hammond Jr.*, M. K. Pangburn, V. K. Mishra, D. A. Johnson, A. E. Rusiñol, and A. Agrawal. Exposing a hidden functional site of C-reactive protein by site-directed mutagenesis. J. Biol. Chem. 287:3550-3558, 2012.
  10. Gang, T. B., D. J. Hammond Jr., S. K. Singh, D. A. Ferguson, Jr., V. K. Mishra, and A. Agrawal. The phosphocholine-binding pocket on C-reactive protein is necessary for initial protection of mice against pneumococcal infection. J. Biol. Chem. 2012 (in press).

Note: *First Author 

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