Immunology Graduate Group

Bruce D. Freedman V.M.D., Ph.D.
Associate Professor, Pathobiology

Address: Rm 368E Old Vet Building, 3800 Spruce Street
Office Phone: (215) 573-8218
Lab Phone: (215) 573-8219
Fax: (215) 898-0719
Email: bruce@vet.upenn.edu

Education:
Ph.D., University of Pennsylvania
VMD, University of Pennsylvania
M.S., Pennsylvania State University
B.S., Dickinson College

Research Interests

Signal transduction mechanisms in immune cells

Research Summary

The general focus of the laboratory is physiological processes that regulate lymphocyte and macrophage development and function. We are specifically interested in pathways that regulate calcium signaling in T and B cells and the mechanisms by which diverse and complex inputs (antigen and coactivating and inhibitory stimuli) are encoded as functionally specific Ca2+ signals and translated into appropriate biological responses that regulate lymphocyte development and differentiation. We are also interested in the viral and cellular determinants of viral tropism and pathogenesis. We have focused on the signal transduction pathways activated in human macrophages and T cells by HIV-1 envelope protein (gp120) upon interaction with CD4 and chemokine receptors. Our goal is to understand the functional consequences of signaling on virus entry, post-entry steps of viral replication, and the consequences on target cell functions apart from infection.

Selected Publications

1. Freedman, B.D. , Price, M. and Deutsch C., 1992. Evidence for voltage modulation of IL-2 production in mitogen-stimulated human peripheral blood lymphocytes. Journal of Immunology. 149:3784-3794.

2. Freedman, B.D. , Fleischmann, B.K., Punt, J., Hashimoto, Y., Gaulton, G., and Kotlikoff, M.I., 1995. Identification of Kv1.1 expression by murine CD4 - CD8 - thymocytes: A role for voltage-dependent K + channels in murine thymocyte development. Journal of Biological Chemistry . 270:22406-22411.

3. Freedman, B.D. , Liu Q.H., Gaulton, G., Kotlikoff, M.I., Heschler, J., and Fleischmann, B.K., 1999. ATP-evoked Ca 2+ transients and currents in murine thymocytes: Possible role for P2X receptors in death by neglect. European J.l of Immunol . 29:1635-1646.

4. Freedman, B.D. , Liu, Q.H., Somersan, S., Kotlikoff, M.I., and Punt, J.A., 1999. Receptor avidity and costimulation specify the Ca 2+ i signaling pattern in CD4 + CD8 + thymocytes. Journal of Experimental Medicine . 190:943-953.

5. Liu, Q-H, Williams, D. A., McManus, C., Baribaud, F., Doms, Schols, D., De Clercq, E.R. W., Kotlikoff, M. I., Collman R. G., and Freedman B. D. , 2000. HIV-1 gp120 and chemokines activate ion channels in primary macrophages through CCR5 and CXCR4 stimulation. Proceedings of the National Academy of Sciences . 97:4832-4837.

6. Liu, Q-H, Fleischmann, B.K., Hondowicz, B., Maier, C., Turka, L., Yui, K., Kotlikoff, M.I., Wells, A.D., and Freedman, B.D., 2002. Modulation of Kv channel expression and function by TCR and costimulatory signals during peripheral CD4 + lymphocyte differentiation. J. Experimental Medicine . 196: 897-909.

7. Wells, A.D., Liu, Q-H, Hondowicz, B.H., Zhang, J., Turka, L.A. , and Freedman, B.D., 2003. Regulation of T cell activation and tolerance by PLC g 1-dependent integrin avidity modulation. Journal of Immunology . 170:4127-4133.

8. Liu, Q-H., Liu, X., Wen, Z., Hondowicz, B., King, L.B., Monroe , J., and Freedman, B.D . , 2005. Distinct calcium channels regulate responses of primary B lymphocytes to BCR engagement and mechanical stimuli . Journal of Immunology. 174:68-792.

9. Zhu, P., Liu, X., Labelle, E., Freedman, B.D. ,2005. Mechanisms of hypotonicity-induced calcium signaling and integrin activation by arachidonic acid-derived inflammatory mediators in B cells. Journal of Immunology . 175:4981-4989.

10. Liu, X., Zhu, P., Freedman, B.D., 2005. Multiple eicosanoid-activated non-selective cation channels regulate B cell adhesion to integrin ligands. (in press, American Journal of Physiology, Cell Physiology).

 

 

Biomedical Graduate Studies | University of Pennsylvania | Contact