Rawal, Nenoo, Ph.D.

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Contact: nenoo.rawal@uthct.edu

Research Interest:
C5 Convertases of the Human Complement System

Current Projects:

1. Activation and regulation of the lectin pathway of complement (NIH).
2. Activation and control of the classical pathway of complement (AHA).

Complement Technology, Inc.
Complement Technology, Inc. was formed to continue supplying the medical research community with the highest quality reagents for complement research. CompTech has purchased the entire complement business from Advanced Research Technologies, Inc. of San Diego, California. CompTech and ART have established a formal ongoing relationship to guarantee a smooth transition. The owners and operators of CompTech have a combined experience of 65 years in the complement field. We plan to continue to be the lowest cost supplier of the highest quality reagents available. We will expand the line of reagents to meet the changing needs of research. We would welcome suggestions on how best to do this.

Lay Summary:
The "complement system" is a part of the human immune system which helps fight infections. There are three pathways of complement activation: the classical pathway, the alternative pathway, and the lectin pathway. Activation of the lectin pathway of complement is one of the body’s innate immune responses to infections and plays a major protective role during the vulnerability window experienced by infants between decay of maternal antibody and establishment of an antibody dependent immune system. Lectin pathway activation depends on the binding of mannan binding lectin (MBL) to sugar residues present on the cell surface of microorganisms. Mutations in MBL result in allelic forms of MBL that are associated with serious infections in children and adults. The allelic forms of MBL occur frequently in certain populations. Our laboratory is interested in studying how mutations alter the biological functions of MBL resulting in dysfunctional complement activation and/or disruption of MBL-mediated phagocytosis.

Research Overview:
The complement system consists of about 35 different proteins that circulate in blood or reside on cells as inactive molecules. Bacteria or immune complexes activate complement to initiate a series of reactions in which one complement component activates another, causing a cascade of events. Products generated during the activation process elicit cellular responses such as phagocytosis and inflammation that help fight the infection. Complement activation ultimately results in assembly of the cytolytic membrane attack complex, which then lyses targeted bacteria. Excessive or unwanted activation of complement contributes to the pathogenesis of several immuno-inflammatory diseases and certain life threatening conditions, including glomerulonephritis, rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, tissue graft rejection, reperfusion injury, heart attacks and strokes. It is therefore in the interest of medicine to be able to control complement activation. There is no single inhibitor of all three pathways of complement activation. Our long-term goals are to understand activation and control of complement by studying the properties of complement enzymes, C3/C5 convertases, responsible for generating products which normally initiate important defensive but occasionally pathologically inflammatory reactions. Results from this research will enhance our understanding of the biochemical mechanisms that regulate complement activation and thereby foster design of effective therapies for preventing complement mediated inflammation leading to tissue damage.

Selected Papers and Abstracts:

• Rawal, N. (2004). Complement. Encyclopedia of Respiratory Medicine. (chapter, communicated).
• Rawal N, Pangburn MK. (2003). Formation of high affinity C5 convertase of the classical pathway of complement. J. Biol. Chem. 278, 38476-38483.
• Pangburn M K, and Rawal N. (2002). Structure and function of complement C5 convertase enzymes. Biochem. Soc. Transactions. 30 , 1006-1010.
• Rawal, N, Pangburn MK. (2001). Formation of high affinity C5 convertases of the alternative pathway of complement. J. Immunol. 166 , 2635-2642.
• Rawal N, Pangburn, MK. (2001). Structure/function of C5 convertases of complement. Immunopharmacology. 1 , 415-422.
• Rawal N, Pangburn, MK. (2000). Functional role of the non-catalytic subunit of complement C5 convertase. J. Immunol., 164 , 1379-1385.
• Jobe DA, Rawal N, Schell R F, and Callister SM. (1999). Detection of borreliacidal antibodies in lyme borreliosis sera containing antimicrobial agents. Clinical and Diagnostic Laboratory Immunology. 6 (6): 930-933.
• Sahu A, Rawal N, Pangburn MK. (1999). Inhibition of complement by covalent attachment of rosmarinic acid to activated C3b. Biochem Pharmacol 57:1439-1446, 1999.
• Rawal N and Pangburn MK. (1998). C5 convertase of the alternative pathway of complement. Kinetic analysis of the free and surface-bound forms of the enzyme. J Biol Chem 273: 16828-16835.
• Rawal N, Lee YJ, Whitaker JN, Park JO, Paik WK, Kim S. (1995). Urinary excretion of NG-dimethylarginines in multiple sclerosis patients: preliminary observations. J. Neuro. Sci., 129 , 186-191.