Joseph El Khoury, M.D.
Physician Investigator (Cl)
Center for Immunology and Inflammatory Diseases, Research Institute
Associate Professor of Medicine
Harvard Medical School
Infectious Disease, Massachusetts General Hospital
|MD American University of Beirut 1987|
Dr. El Khoury’s laboratory focuses on studying the role of macrophages and microglia in Neurodegeneration, host defense and inflammation. We are investigating the mechanisms by which modified-self proteins such as β-amyloid (Aβ) and non-self infectious pathogens (Staphylococcus Aureus and Cryptococcus neoformans) interact with microglia and macrophages, how they activate these cells to produce pro-inflammatory molecules and how microglia and macrophages are recruited to sites of deposition of Aβ and infections.
Dr. El Khoury’s previous work showed that macrophage and microglial scavenger receptors such as SRA and CD36 promote binding of microglia and macrophages to infectious microorganisms and Aβ. We have also found that different scavenger receptors play complementary roles in mediating interactions of macrophages with these proteins and pathogens. We are currently extending these studies to determine if SRA, CD36 and various other scavenger receptors such SRF, Lox-1 and MARCO collaborate with other receptors involved in innate immunity such as Toll-like receptors, to determine the role of such interactions in mediating intracellular signaling induced by infectious microorganisms and Aβ.
In addition, we are also looking at the role of chemokines such as MCP-1 and Fractalkine, and their chemokine receptors expressed on macrophages and microglia such as CCR2 and CX3CR1 in the recruitment of these cells to sites of inflammation and infection. We have found that interactions of infectious particles or organisms and Aβ with scavenger receptors promote production of these chemokines, suggesting that the interactions of infectious pathogens and modified self proteins with scavenger receptors are involved in the recruitment of inflammatory cells to sites of infection and injury. We use mouse models for bacterial, fungal and neurodegenerative disorders to perform these studies and delineate the role of these molecules in vivo.