Cell Biology & Molecular Genetics
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   Kenneth Frauwirth


Ph.D., University of California-Berkeley
(301) 405-2507
Fax:  (301) 314-9489

Research Interests:  T cell activation and peripheral tolerance mechanisms; regulation of lymphocyte metabolism.

The immune system has evolved to rapidly respond to a tremendous variety of substances, known collectively as antigens, in part by including a randomized component to the surface molecules involved in recognition by two types of cells, the B and T lymphocytes (also called B and T cells). While this allows B and T cells to respond to antigens never previously encountered, it introduces the problem that there is no intrinsic way for these cells to distinguish between antigens from harmful organisms and those which are completely innocuous, including the body’s own tissues. There must therefore be mechanisms preventing B and T cells from normally responding to harmless antigens, and these mechanisms are collectively referred to as immune tolerance. My laboratory is interested in understanding how T cells differentially respond to antigens that lead to tolerance vs. those that lead to a productive immune response. Some molecules/pathways of particular interest are (1) cyclic AMP signaling, (2) Fyn kinase activation, and (3) regulation of calcium flux. An additional interest is in the regulation of T cell metabolism in tolerant vs. responsive T cells.
The establishment of immune tolerance to self and many foreign antigens is necessary for proper health, and so it is not surprising that improper regulation of tolerance mechanisms can contribute to diseases. In autoimmune disorders, such as rheumatoid arthritis and multiple sclerosis, there are break-downs in tolerance, allowing the immune system to attack other tissues of the body. Similarly, allergies represent a failure in tolerance to otherwise harmless environmental antigens. Conversely, the ability of tumor cells to evade the immune system may be due, in part, to their skill at inducing tolerance. A long-term goal of research in the Frauwirth lab is aimed at being able to manipulate tolerance in a therapeutic setting. To this end, a project is being initiated to utilize knockout and RNA interference technologies to alter T cell tolerance/activation balances in T cells.

Selected Publications:

Frauwirth, K.A., Alegre, M.-L., and Thompson, C.B. (2000). Induction of T cell anergy in the absence of CTLA-4/B7 interaction. J. Immunol. 164:2987-2993

Rathmell, J.C., Vander Heiden, M., Harris, M., Frauwirth, K.A., and Thompson, C.B. (2000). In the absence of extrinsic signals, nutrient utilization by lymphocytes is insufficient to maintain either cell size or viability. Molecular Cell 6:683-692

Alegre, M.-L., Frauwirth, K.A., and Thompson, C.B. (2001). T Cell Regulation by CD28 and CTLA-4. Nature Rev. in Immunol. 3:220-228

Frauwirth, K.A., Alegre, M.-L., and Thompson, C.B. (2001). CTLA-4 is not required for induction of CD8+ T cell anergy in vivo. J. Immunology 167:4936-4941

Frauwirth, K.A., Riley, J.L., Harris, M.H., Parry, R.V., Rathmell, J.C., Plas, D.R., Elstrom, R.L., June, C.H., and Thompson, C.B. (2002). The CD28 signaling pathway regulates glucose metabolism. Immunity 16:769-777

Frauwirth, K.A. and Thompson, C.B. (2002). Activation and inhibition of Tlymphocytes by costimulation. J. Clin. Invest. 109:295-299

Wang, Y.L., Frauwirth, K.A., Rangwala, S.M., Lazar, M.A., and Thompson, C.B. (2002). Thiazolidinedione-Activation of Peroxisome Proliferator-Activated Receptor Can Enhance Mitochondrial Potential and Promote Cell Survival. J. Biol. Chem. 277:31781-31788


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