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Sangwon V. Kim
Irvington Institute Fellowship Program of the Cancer Research Institute
Ph.D. Immunobiology, Yale University 2005
Sangwon.kim@med.nyu.edu

During my Ph.D., I studied the function of Myo1f in immune cells in Richard Flavell's lab at Yale. Myo1f was found in my attempt to search for genes upregulated in CD4 memory T cells compared to CD4 naive T cells. Myo1f is a member of non-filamentous, actin-binding motors and its expression is enriched in lymphoid tissues. I found out that Myo1f-deficient neutrophils underwent abnormally increased exocytosis of beta2 integrin-containing granules, resulting in increased adhesion and reduced motility. This abnormality seemed to be related to decreased cortical F-actin in Myo1f-deficient cells, which normally inhibit granule exocytosis. In addition, Myo1f-deficient mice showed defective neutrophil response to infection by Listeria monocytogenes and exhibited increased susceptibility, suggesting a critical role of Myo1f in maintaining proper motility of immune cells.
 
Orphan nuclear hormone receptor, RORgt, has been shown to be important in Th17 cell differentiation. However, RORgt null mice have additional defects in lymphoid organogenesis and double-positive thymocyte differentiation, making them difficult to be used to study Th17 cells in vivo. Therefore, I have generated RORg floxed mice for a conditional deletion of RORgt or RORg. Currently, tissue-specific or inducible deletion of RORgt and its effect on IL-17 production is being tested.
 
At steady state, a significant number of Th17 cells and other subsets of T cells exist in the gut lamina proria  where homeostasis of these T cell subset is important to distinguish the harmful bacteria from commensal ones. Disturbance in this homeostasis can cause local autoimmune diseases such as colitis. I am interested in the mechanism of T cell homing to gut lamina propria and potential chemokine receptors involved in this process are being investigated.

Publications

Krendel M*, Kim SV*, Willinger T, Wang T, Kashgarian M, Flavell RA, Mooseker MS. Disruption of Myosin 1e promotes podocyte injury. J Am Soc Nephrol. 2009 Jan;20(1):86-94. (*:equal contribution)

Kim SV, Flavell RA. Myosin I: From yeast to human. Cell. Mol. Life Sci. 2008 Jul;65(14):2128-37.

Kim SV, Mehal WZ, Dong X, Heinrich V, Pypaert M, Mellman I, Dembo M, Mooseker MS, Wu D, Flavell RA. Modulation of cell adhesion and motility in the immune system by Myo1f. Science 2006 Oct 6;314(5796):136-9.

Kim SV, and Flavell RA. CD8alphaalpha and T cell memory. Science 2004 Apr 23;304(5670):529-30.

Blander JM, Sant'Angelo DB, Metz D, Kim SV, Flavell RA, Bottomly K, Janeway CA Jr. A pool of central memory-like CD4 T cells contains effector memory precursors. J. Immunol. 2003 Mar 15;170(6):2940-8.

Chae WJ, Lee HK, Han JH, Kim SV, Bothwell AL, Morio T, Lee SK. Qualitatively differential regulation of T cell activation and apoptosis by T cell receptor zeta chain ITAMs and their tyrosine residues. Int. Immunol. 2004 Sep;16(9):1225-36.

Lim JH, Kim SV, Song YS, Lee SK. Induction of late activation events by Igbeta signaling subunit of B cell receptor in Jurkat T cell without tyrosine phosphorylation. Mol. Cells 1998 8(4):408-415.