Iowa State University
Department of Genetics, Development and Cell Biology
1210 Molecular Biology Building
Ames, Iowa 50011-3260
Phone: 515-294-7322
Fax: 515-294-6755
Email:
Michael McCloskey
Associate Professor
Dr. McCloskey received his B.S. in Plant Science from U.C. Riverside and his Ph.D. in Biochemistry from U.C. Davis. After postdoctoral work in membrane biophysics at Stanford and U.C. Irvine, he held a research appointment at Irvine before joining ISU in 1989.
Research Description
Our research deals with membrane physiology and signal transduction in mast cells and more recently, neural progenitors. Allergic reactions are initiated when mast cells detect allergens via their FcεRI receptor for Immunoglobulin E (IgE). Allergic rhinitis and other forms of hypersensitivity also can be classically conditioned to occur in response to IgE-independent stimuli such as odors. We seek to identify the ultimate steps, i.e., the route of delivery and nature of the signal, by which the nervous system controls mast cell responses to conditioned stimuli. Some evidence points to a contribution of mast cell P2Y receptors, which we have shown regulate chemotaxis, open G protein-gated K+ channels, and amplify IgE-coupled secretion of inflammatory mediators. We are also exploring the contribution of P2Y receptors to mast cell-neuron interactions that drive expulsion of intestinal worm parasites. We recently determined the developmental expression of Kv channel subtypes in brain progenitors during neuronal differentiation, showing that particular beta subunits previously thought to be neuronal are present and functional in the undifferentiated progenitors. Two of our previous contributions to mast cell biology were to demonstrate that CRAC channels mediate FcεRI-driven Ca2+ influx, and that the NF-AT transcription factor, which until then was thought to be active only in lymphocytes, is activated in mast cells by the FcεRI-triggered calcium influx. Biophysical problems we have addressed include the role of polyisoprenoid lipid mobility in glycosylation reactions, external constraints on lateral diffusion of the FcεRI, and the mechanism by which the attack complex of complement permeabilizes membranes.
Contact Information:
540 Science Hall II
Ames, IA 50011-3223
515-294-5925 voice
515-294-8457 fax
Education:
B.S., University of California, Riverside, 1974
Ph.D., University of California, Davis, 1979
Publications
Li, H.W., M. McCloskey and E.S. Yeung. 2006. Real-time dynamics of label-free single mast cell granules revealed by differential interference contrast microscopy. Anal. Bioanl. Chem. .
McCloskey, M.A. and L. Zhang. 2000. Potentiation of FceRI-activated Ca2+ current (Icrac) by cholera toxin: Possible mediation by ADP-ribosylation factor. J. Cell Biol. 148(1): 137-146.
McCloskey M.A., Fan, Y. and S. Luther. 1999. Chemotaxis of rat mast cells towards adenine nucleotides. J. Immunology 163(2): 970-977.
Lillard, S. J., Yeung, E. S. and M. A. McCloskey. 1996. Monitoring exocytosis and release of serotonin from individual mast cells by capillary electrophoresis with laser-induced native fluorescence detection. Anal. Chem. 68, 2897-2904.
Zhang, L. and M.A. McCloskey. 1995. Immunoglobulin E receptor-activated calcium conductance in rat mast cells. J. Physiol. (London) 483.1:59-66.
Hutchinson, L.E. and M.A. McCloskey. 1995. FceRI-mediated induction of nuclear factor of activated T cells. J. Biol. Chem. 270(27):16333-16338.
Fan, Y. and M.A. McCloskey. 1994. Dual pathways for GTP-dependent regulation of chemattractant-activated K conductance in murine J774 monocytes. J. Biol. Chem. 269(50):31533-31543.
McCloskey, M.A. and Y.-X. Qian. 1994. Selective expression of potassium channels during mast cell differentiation. J. Biol. Chem. 269(20):14813-14819.