David Geffen School of Medicine at UCLA

Undergraduate Education	University of California, Irvine
Graduate Education	University of California, Los Angeles Ph.D., Microbiology, Immunology, and Molecular Genetics
Research Interest	The primary objective of my research it to understand how the family of Toll-like receptors (TLRs) helps modulate the direct functions of the innate immune system such as phagocytosis, and the indirect functions such as T cell activation. Recently we discovered that activation of human peripheral blood monocytes through TLRs triggers their differentiation into distinct populations of DC-SIGN+CD16+ macrophages and CD1b+ dendritic cells. DC SIGN+CD16+ macrophages are phagocytic, capable of both the binding and uptake of mycobacteria. Therefore, DC-SIGN+ macrophages represent a population of cells capable of carrying out the direct function of the innate immune response. In contrast, CD1b+ dendritic cells express critical T cell co-stimulatory molecules, secrete cytokines such as the Th1 skewing IL-12 and potently trigger T cell activation. Therefore, CD1b+ dendritic cells represent a population of cells capable of carrying out the indirect function of the innate immune system, triggering T cell activation, and bridge the innate and adaptive immune responses. Current studies are aimed at further elucidating the distribution and function of DC-SIGN+ macrophages and CD1b+ dendritic cells in normal and diseased tissue and their role in combating microbial infections.

Selected Publications

1. Krutzik SR, Ochoa MT, Sieling PA, Uematsu S, Ng YW, Legaspi AJ, Liu PT, Cole ST, Godowski PJ, Maeda Y, Sarno EN, Norgard MV, Brennan PJ, Akira S, Rea TH, Modlin RL. Activation and regulation of toll-like receptor 2 and 1 in human leprosy. Nature Medicine 2003 May; 9(5): 525-532.

2. Kim J, Ochoa MT, Krutzik SR, Takeuchi O, Uematsu S, Legaspi AJ, Brightbill HD, Holland D, Cunliffe WJ, Akira S, Sieling PA, Godowski PJ, Modlin RL. 2002. Activation of toll-like receptor 2 in acne triggers inflammatory cytokine responses. J Immunol. Aug 1;169(3):1535-1541

3. Brightbill HD, Libraty DH, Krutzik SR, Yang RB, Belisle JT, Bleharski JR, Maitland M, Norgard MV, Plevy SE, Smale ST, Brennan PJ, Bloom BR, Godowski PJ, Modlin RL. 1999. Host defense mechanisms triggered by microbial lipoproteins through toll-like receptors. Science 285, 732-736

4. Krutzik SR, Tan B, Li H, Ochoa MT, Liu PT, Sharfstein SE, Graeber TG, Sieling PA, Liu YJ, Rea TH, Bloom BR, Modlin RL. TLR activation triggers the rapid differentiation of monocytes into macrophages and dendritic cells. Nature Medicine Jun; 11(6):653-60, 2005.