Medical Student Research Fellowship for Summer 2007

Mentor: David R. Karp, MD, PhD
Department: Internal Medicine - Rheumatology
Room number: Y8.302
Mail Code: 8884
Phone number: 8-9110
E-mail: David.Karp@UTSouthwestern.edu
Project title: Influence of C-Reactive Protein on Dendritic Cell Maturation

Human subjects IRB approved project number (where applicable): 0701-385

Animal subjects IRB approved project number (where applicable):

Project Type (patient-based research, animal-based research, or basic research; this characterization is only to permit a general classification for grouping similar types of projects)

Basic research

Brief Description of Project:

C-reactive protein (CRP) is an acute phase reactant synthesized in response to a inflammatory stimuli. It has recently been shown that receptors for immunoglobulin (FcR) are also receptors for CRP, and that this interaction on endothelial cells leads to down-regulation of nitric oxide (NO) synthesis. The result is that blood vessels are less elastic and predisposed to the development of hypertension and atherosclerosis. An unanticipated finding was that this pathway involves angiotensin and the AT2 receptor.

This project will extend these findings from endothelial cells to cells in the immune system. Myeloid dendritic cells (DC) are potent antigen presenting cells that express both FcR and AT2. Monocytes will be isolated from peripheral blood of normal volunteers and cultured under conditions that cause them to become immature DC. The effect of CRP on this process will be measured using flow cytometry and biochemical assays. The role of angiotensin and the AT2 receptor will be elucidated using specific inhibitors and siRNA. Finally, model systems using transfected cells will help to determine the effect of CRP on DC development and function. The results of these studies will help to explain why patients with auotimmmue disorders have higher rates of cardiovascular disease.

Previous Research Activities or Publications with Medical Students:

PA Garza, JC Jones, J Guthridge, VM Holers, and DR Karp (2000) Generation of novel C3dg tetramers for the analysis of CD21 binding and function. Arth Rheum 43:S396.

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