 |
Maria Febbraio, Ph.D.Associate Staff
Department of Cell Biology |
Area of General Research Interest
The focus of research in my laboratory is CD36, a class B scavenger receptor involved in numerous physiologic and pathologic processes. The research topics currently under study are:
- The Role of CD36 in Atherosclerosis and Macrophage Biology
- The Role of CD36 in Diabetes
- The Role of CD36 in Fatty Acid Metabolism
Current Program
Characterization of atherosclerosis in murine models using different diets. Characterization of macrophage immune response and parameters of lipid flux, using cells from numerous murine models. Defining the impact of decreased fatty acid utilization on heart and other organs in murine models.
Investigators
- George Nimako, Lead Technologist
- Kristen Nowak, Technician
Brief Description
My research focuses on a membrane glycoprotein, CD36. CD36 is expressed on many cells and tissues. including monocytes/macrophages, adipocytes, platelets, endothelial cells, cardiac and skeletal muscle, and retinal pigment epithelial cells. It has multiple functions, including recognition of apoptotic cells and modified lipids, uptake of fatty acids and regulation of angiogenesis.
Past work in our laboratory has established a key role for CD36 in the pathogenesis of atherosclerosis. Recent work in this laboratory and others has uncovered a role for CD36 in diabetes. Because CD36 is expressed on cells and tissues important to lipid and fatty acid metabolism, we believe it may be an important sensor of metabolic state. We have developed genetically engineered murine models to test specific hypotheses related to these disease states.
We also have active ongoing studies on the role of CD36 in physiologic and pathologic angiogenesis, again using genetically engineered murine models. These studies have particular relevance to tumor biology and dysfunctional angiogenesis of diabetes. Although a large part of my laboratory focuses on in vivo animal study, we also study cells derived from these animals and from humans to delineate CD36-dependent signaling pathways and to study the trafficking of CD36-dependent ligands.
With collaborators, we are investigating the role of CD36 in brain and heart ischemia and in the pathogenesis of malaria.
Recent publications
Febbraio M, Silverstein RL. CD36: Implications in cardiovascular disease. Int J Biochem Cell Biol 2007;39:2012-30.
Kuchibhotla, S., Vanegas, D., Kennedy, D.J., Guy, E., Nimako, G., Morton, R.E., and Febbraio, M. Absence of CD36 protects against atherosclerosis in apoE knock-out mice with no additional protection provided by absence of SR-AI/II. Cardiovascular Res., in press.
Koonen, D.P.Y., Jacobs, R.L., Febbraio, M., Young, M.E., Ong, H., Vance, D.E., Dyck, J.R.B. Increased Hepatic CD36 Expression Contributes to Dyslipidemia Associated with Diet-Induced Obesity. Diabetes, (29 Aug 2007 epub) in press.
King, K., Stanley, W.C., Febbraio, M. Fatty Acid Oxidation in Cardiac and Skeletal Muscle Mitochondria is Unaffected by Deletion of CD36. Archives of Biochemistry and Biophysics, 467, 234-8 (2007).
Koonen, D.P.Y., Febbraio, M., Bonnet, S., Michelakis, E.D., Dyck, J.R.B. Increased Glucose Oxidation Attenuates Age-dependent Decreases in Cardiac Performance and Prevents Cardiac Hypertrophy, Circulation, 116, 2139-47 (2007).
Podrez, E.A., Byzova, T.V., Febbraio, M., Salomon, R.G., Ma, Y., Valiyaveettil, M., Poliakov, E., Sun, M., Finton, P.J., Curtis, B.R., Chen, J., Zhang, R., Silverstein, R.L., Hazen, S.L. CD36 modulates platelet reactivity in vivo during hyperlipidemia: A mechanism linking hyperlipidemia, oxidant stress and a pro-thrombotic phenotype. Nature Medicine, 13. 1086-95 (2007).
Guy, E., Kuchibhotla, S., Silverstein, R.L., Febbraio, M. Continued inhibition of atherosclerotic lesion development in long term western diet fed CD36o/apoEo mice. Atherosclerosis, 193, 123-30 (2007).
Greenberg ME, et al. Oxidized phosphatidylserine-CD36 interactions play an essential role in macrophage-dependent phagocytosis of apoptotic cells. J Exp Med 2006;203:2613-25.
Rahaman, S.O., Lennon, D.J., Febbraio, M., Podrez, E.A., Hazen, S.L., Silverstein, R.L. A CD36 dependent signaling cascade is necessary for macrophage foam cell formation. Cell Metabolism, 4:211-21 (2006).