Maria Febbraio , Ph.D. Associate Staff Department of Molecular Cardiology Lerner Research Institute / NB50 9500 Euclid Avenue Cleveland, Ohio 44195 Telephone: (216) 445-5605 Fax: (216) 445-8204 febbram@ccf.org

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 Inflammation in CD36 mediated Atherosclerosis
• The Role of CD36 in Obesity, Insulin Resistance and the Metabolic Syndrome
• The Role of CD36 in Fatty Acid Metabolism

Current program:

• Investigation of the mechanisms by which diseases and states characterized by increased or chronic inflammation lead to atherosclerosis using murine models
• Currently, we are using models of smoking (nicotine), periodontal disease and inflammatory bowel disease to investigate mechanisms that accelerate atherosclerosis.
• Investigation of the role of CD36 in obesity, insulin resistance and the metabolic syndrome using tissue specific CD36 KOs.
• Defining the impact of impaired fatty acid utilization in heart on cognitive function.

Investigators:

• Brown, Paul M., Ph.D., Sr. Research Technologist

Brief Description:

The focus of my lab is a transmembrane glycoprotein present on numerous cell types, called CD36. CD36 is involved in a remarkable number of cellular processes. For example, CD36 is a member of a class of proteins called scavenger receptors, and thus has functions which include a role in innate immunity (by scavenging organisms with repetitive motifs), and normal homeostasis (uptake of apoptotic cells and photoreceptor rod outer segments). CD36 facilitates fatty acid uptake in muscle and fat, and thus plays an important role in energy substrate choice and utilization. CD36 also recognizes modified forms of LDL which are atherogenic, and plays a role in the pathogenesis of this disease. Finally, CD36 plays a role in fatty acid uptake in fat, muscle and liver, and interacts with pathogenic ligands which may impact insulin signaling. My lab has created numerous mouse models to investigate in vivo mechanisms by which CD36 functions in normal and pathological processes. Because CD36 has a wide variety of functions, the work in my laboratory utilizes many different techniques and spans multiple disciplines.

Key References:

Koonen, D.P., Sung, M.M., Kao, C.K., Dloinsky, V.W., Koves, T.R., Ilkayeva, O., Jacobs, R.L., Vance, D.E., Light, P.E., Muoio, D.M., Febbraio, M., Dyck, J.R.  Alterations in skeletal muscle fatty acid handling predisposes middle-aged mice to diet induced insulin resistance.  Diabetes, 59:1366-75 (2010). PMID:20299464

Bieghs, V., Wouters, K., van Gorp, P.J., Gijbels, M.J., de Winther, M.P., Binder, C.J., Lütjohann, D., Febbraio, M., Moore, K.J., van Bilsen, M., Hofker, M.H., Shiri-Sverdlov, R.  Role of Scavenger Receptor A and CD36 in diet-induced non-alcoholic steatohepatitis in hyperlipidemic mice.  Gastroenterology, 138:2477-86 (2010). PMID:20206177

Song, B.J., Elbert, A., Rahman, T., Orr, S., Chen, C.T., Febbraio, M., Bazinet R.P.  Genetic ablation of CD36 does not alter mouse brain polyunsaturated fatty acid concentrations.  Lipids, 45:291-9 (2010). PMID:20306148

Kennedy D.J., Kuchibhotla S.D., Guy E., Park Y.M., Nimako G., Vanegas D., Morton R.E., Febbraio M. Dietary Cholesterol Plays a Role in CD36-Mediated Atherogenesis in LDLR-Knockout Mice.  Arterioscler Thromb Vasc Biol. 29, 1481-7 (2009). PMID:19608973

Park Y.M., Febbraio M., Silverstein R.L.  CD36 modulates migration of mouse and human macrophages in response to oxidized LDL and may contribute to macrophage trapping in the arterial intima.  J Clin Invest. 119:136-45 (2009). PMID:19065049

Chen K, Febbraio M., Li W., Silverstein R.L. A Specific CD36-Dependent Signaling Pathway Is Required for Platelet Activation by Oxidized Low-Density Lipoprotein.  Circ Res.102, 1512-9 (2008).

Kuchibhotla, S., Vanegas, D., Kennedy, D.J., Guy, E., Nimako, G., Morton, R.E., Febbraio, M.  Absence of CD36 protects against atherosclerosis in apoE KO mice with no additional protection provided by absence of SRAI/II.  Cardiovasc. Res., 78, 185-196 (2008).

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).