Our Science – Hwang Website

Sam T. Hwang, M.D., Ph.D.

Dermatology Branch Senior Investigator Building 10, Room 12N238 NCI-Bethesda Bethesda, MD 20892 Phone:   301-496-8724 Fax:   301-496-5370 E-Mail:   hwangs@mail.nih.gov

Biography

Dr. Hwang received his M.D. from Harvard Medical School and his Ph.D. in biochemistry from the University of Basel in Switzerland. He completed a medical internship at the Brigham and Women's Hospital and a dermatology residency at the University of California at San Francisco (UCSF). He continued there as a Howard Hughes Physician Fellow in the laboratory of Dr. Steven D. Rosen, studying the role of L-selectin in signaling the activation of T lymphocytes as part of normal recirculation in peripheral lymph nodes. He served as clinical instructor and associate physician in the Department of Dermatology at UCSF prior to coming to the NIH in 1997. Dr. Hwang was honored by the American Academy of Dermatology with a Young Investigator in Dermatology Award in 1996 and became a tenure track investigator in the Dermatology Branch in 1997. He received tenure in 2003.

Research

Chemokine receptors in immune cell trafficking and cancer metastasis

Dr. Hwang's work focuses on the biology of immune cell trafficking to and from skin in inflammatory and neoplastic processes with a particular emphasis on the roles of chemoattractant cytokines (also known as chemokines), chemokine receptors, and adhesion molecules. Initial studies in his laboratory have addressed the question of how antigen-presenting cells or dendritic cells (DC) of skin leave the skin after being triggered by inflammatory signals or antigens. He has found that a chemokine named secondary lymphoid tissue chemokine (SLC) and its receptor, CCR7, play significant roles in this process by recruiting activated DC into afferent lymphatic vessels. The emigration process appears to be regulated by altering the expression of CCR7 such that it is strongly upregulated by inflammatory conditions in which DCs leave the skin. His laboratory has also shown that cancer cells can also use CCR7 to increase metastasis to regional draining lymph nodes. By understanding the mechanisms through which DCs leave skin and enter lymph nodes, scientists may develop strategies for implementing more effective dendritic cell vaccines and therapies.

Dr. Hwang has also discovered that DCs express chemokines as they become activated. In particular, his laboratory has detailed the expression of a novel membrane-bound chemokine called fractalkine on maturing DCs. This molecule is strongly upregulated by maturing DCs and is still associated with DCs in peripheral secondary lymphoid tissues such as tonsil. Interestingly, a subset of T cells expresses the fractalkine receptor, and thus it is possible that fractalkine mediates the cell-cell binding/communication between DCs and T cells.

Dr. Hwang has also investigated the role of endothelial cell-produced chemokines in the adhesion of memory T cells to inflamed blood vessels in skin. Using a dynamic parallel plate flow chamber system, his laboratory has shown the CC chemokine, liver and activation-regulated chemokine (LARC), plays a critical role in the firm attachment of CCR6-positive human memory T cells to activated dermal endothelial cells.

Dr. Hwang has recently focused his work on the role of chemokine receptors in cancer metastasis. Using the B16 murine melanoma model and retroviral transduction of B16 cells with genes encoding the chemokine receptors, CXCR4, CCR10, and CCR7, his laboratory has shown that each of these chemokine receptors play non-redundant roles in melanoma metastasis. CCR7, for example, facilitates metastasis of cells from the primary tumor site to regional lymph nodes, while expression of CXCR4 increases lung metastasis. CCR10, when activated by appropriate ligands in the skin, acts to protects B16 cells from Fas-triggered apoptosis, thus protecting cancer cells from immunological attack.


The Hwang Laboratory uses a wide variety of cell biology and molecular biology techniques including transgenic expression of chemokines under skin-specific promoters, fluorescence microscopy, gene expression analysis using glass microarrays, and RT-PCR. Recently, Dr. Hwang has implemented the use of a parallel plate flow chamber assay to simulate blood flow and interactions of leukocytes with endothelial adhesion molecules.

Collaborators in this work are Nicholas Restifo and David Gius, NCI; Nadya Tarasova and Christopher Michejda, NCI-Frederick; and, Andrew Blauvelt, Oregon Health Sciences University.

This page was last updated on 6/11/2008.