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Center of Excellence for Inflammation, Infectious Disease & Immunity

Quillen College of Medicine

Center News

Dr. Alok Agrawal Receives RO1 Grant Award from the National Institute of Health

Rheumatoid arthritis (RA) is an autoimmune disease in which autoantibody-mediated inflammation leads to destruction of the joints. Also, RA patients are more susceptible to cardiovascular disease, such as atherosclerosis. C-reactive protein (CRP) is present in the blood but is also present in the joint fluid of RA patients and in atherosclerotic lesions in the artery. Dr. Alok Agrawal, a professor in the department of Biomedical Sciences at East Tennessee State University has recently received an R01 Grant Award from NIH to investigate the use of modified and engineered CRP molecules that are capable of binding to immune complexes and bad cholesterol, in murine models of RA and atherosclerosis, to control the development of the disease.

CRP has long been known as a marker of inflammation in inflammatory diseases including RA and atherosclerosis. Many doctors recommend that patients with certain risk factors for cardiovascular disease have their CRP levels in the blood measured regularly, in addition to the measurement of cholesterol levels. CRP is also present at the sites of inflammation in inflammatory diseases including RA and atherosclerosis. In fact, while these diseases on the surface seem very different, they are all fundamentally similar due to deposition of proteins collecting at specific parts of the body.

From an evolutionary standpoint, CRP is a very old protein. It is present in animals that were on earth as long as 300 million years ago. This also indicates that the protein must have an important but relatively simple function. The level of CRP in animals with no immune system is also incredibly high when compared with animals with more complex immunity.

There has been a question of what exactly the function of CRP molecules is in the body and why this specific protein is present at the sites of inflammation in inflammatory diseases. Dr. Agrawal thinks he might have the answer. He hypothesizes that there is a molecular connection between all these diseases and how CRP in a persons body reacts. He thinks that CRP may act as a surveillance molecule in your body. When CRP identifies a pathogenic protein, it latches on, helping to trigger the bodys immune response to get rid of the pathogenic protein. He also thinks that CRP molecules change their structure in inflammatory microenvironment and that modified CRP is the functional version of native CRP. In certain peoples body, CRP molecules are unable to change their structure due to inappropriate inflammation and therefore unable to identify and bond with pathogenic proteins, resulting in the disease.

Dr. Agrawal will continue his research on this fascinating subject thanks to a major grant award of 2.7 million dollars from the National Institute of Health (NIH). He has received an R01 award that will continue his research for the next 5 years. A part of this grant ($0.4 million) goes to Dr. Agrawals collaborator, Dr. David Brand, at the University of Tennessee, Memphis.
This grant will allow Agrawal and his team to build human immune models of various inflammatory diseases and then treat those diseases with lab-made modified CRP molecules.

It is hoped that successful completion of Dr. Agrawals research project will reveal whether engineered CRP can help develop a treatment strategy for inflammatory diseases including RA.

Dr. Agrawal Teaching

C Reactive Proteins

 

 

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