Download SORCIN AND RYANODINE RECEPTORS IN HEART FAILURE

Department of Physiology Fall 2003 Seminar Series
M. Saleet Jafri, Ph.D.
Associate Professor
Bioinformatics and Computational Biology
George Mason University
Manassas, VA
Room 5A101, Noon –1:00pm, Thursday, September 18, 2003
Abstract
The activation of T-lymphocytes is the primary response of the immune system to foreign
proteins (antigens). When thus stimulated at the cell surface, a intracellular
signalling cascade results in elevated intracellular calcium concentration in the form of
calcium oscillations. Recent experimental studies have shown that two calcium-dependent
transcription factors, NFAT and NFkB which activate the genes that code for two
different interleukins that are involved in activation of the immune system, are
differentially activated depending on the frequency of the calcium oscillations. In
this study, a mathematical model of the biochemical reaction pathways involved in the
activation of these two transcription factors is developed. Kinetic parameters for the
models are determined by experimental estimates. The models faithfully reproduce a
variety of experimental data and suggest a mechanism for calcium-dependent activation of
transcription factors. Furthermore, these two pathways contain the target for all of the
commonly used immunosuppressants. The model can help to suggest future drug targets for
modulation of the immune response.
Recent Publications:
Jafri, M. S. 1993. A theoretical study of spatial and temporal cytosolic calcium waves. Doctoral
Dissertation-The City University of New York.
Jafri, M. S., S. Vajda, P. Pasik, and B. Gillo. 1992. A membrane model for cytosolic calcium
oscillations: a study using Xenopus oocytes. Biophys. J. 63:235-246.
Jafri, M. S. and B. Gillo. 1994. A membrane potential model with counterions for cytosolic calcium
oscillations. Cell Calcium . 16:9-19.
Jafri, M. S. 1995. A theoretical study of cytosolic calcium waves in Xenopus oocytes. J. Theor. Biol.
172:209-216.
Persons with disabilities who may need auxiliary aids or services are requested to contact Cindy Hutson
(806-743-2520) at least 24 hours prior to this seminar so that appropriate arrangements can be made.