Protein Adducts and Immune Response
Summary: The non-enzymatic post-translational modification of proteins following exposure to reactive aldehydes is well known as a mechanism for altering the immune system's response to proteins. In addition, these types of protein modifications have been hypothesized as key events in the development of autoimmune components of specific diseases such as ethanol-mediated cirrhosis of the the liver. The focus of my previous research has been on the synthesis and characterization of 4-substituted-1,4-dihydropyridine-3,5-dicarbaldehyde protein adducts likely to be formed following exposure to cigarette smoke and evaluating the response of the immune system to these modified proteins with an emphasis on the breaking of immunological tolerance.
Status: As of fall 2012, the project is well established (largely by a single graduate student) and has evaluated the immune response to a test protein (ovalbumin) when modified with several aldehyde and aldehyde combinations. Data indicate that modifications of proteins with chemicals found in cigarette smoke elevate the immune response to the test protein as measured by antibody production. Antibodies produced are specific to the test proteins and to the modification (adduct). The next set of experiments will use an animal model of cigarette smoke exposure to determine if the same immune responses occur.
Opportunities for Students: The synthesis of adducts on proteins, synthesis of small structurally identical molecules, immunizing animals and development of direct and competitive ELISAs are possible areas for the future contributions by undergraduate students to the research.
Additional Information: Information on the adducts associated with cigarette smoke can be found in the publication here.