Ph.D., University of California-Berkeley
Telephone: (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
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
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.
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.
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