Medical Student Research Fellowship for Summer 2008

Mentor: Christoph Wuelfing
Department: Immunology
Room number: NA7.500
Mail Code: 9093
Phone number: 214 648 7320
E-mail: Christoph.Wuelfing@UTSouthwestern.edu
Project title: Promoting NK cell killing of tumor target cells by enhancing NK cell polarization

Human subjects IRB approved project number (where applicable):

Animal subjects IRB approved project number (where applicable): 2008-0019

Project Type (patient-based research, animal-based research, or basic research; this characterization is only to permit a general classification for grouping similar types of projects)

Basic research

Brief Description of Project:
Natural killer (NK) cells are named for their intrinsic ability to kill tumor cells. However, against a lot of tumors NK cells only kill suboptimally. The principal killing mechanism of NK cells is the release of the contents of cytotoxic granules towards the tumor target cell. This requires that the NK cells effectively polarize their secretory machinery. In previous work we have shown that this polarization is often inefficient in the interaction of NK cells with tumor target cells. Drawing on our investigation of the regulation of cellular polarization of a second lymphocyte, the T cell, we have developed a strategy to enhance NK cell polarization as a means to improve tumor target cell lysis. Preliminary data support the validity of the approach. A project will be available in the implementation of the strategy in mouse tumor models. The project includes video fluorescence microscopy to visualize polarization, molecular biology to generate reagents to enhance it, in vitro functional assays for target cell lysis, and potentially mouse work.

Previous Research Activities or Publications with Medical Students:
6 Medical student, the last two were Noah Liwag and Thanh Tran (for the second time) in 2007.

Tskvitaria-Fuller, I., Mistry, N., Sun, S., and Wülfing, C. (2007). Protein transduction as a means of effective manipulation of Cdc42 activity in primary T cells. J. immunol. Meth., 319, 64-78