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BRUCE D. FREEDMAN, V.M.D., Ph.D., M.S., B.S.
Associate Professor (with Tenure), Veterinary School University of Pennsylvania

Director, PennVet Imaging Core Facility, University of Pennsylvania School of Veterinary Medicine

Immunology graduate group, University of Pennsylvania

Research Areas: Calcium, Calcium channels, Calcium Signaling, Signal transduction,
PubMed Link
Contact Information:
368E Old Vet Bldg.
3800 Spruce Street
 Phone (215) 573-8218
 Fax (215) 898-0719
 Email bruce@vet.upenn.edu

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.

Myung, P.S., Jordan, M.S., Punt, J.A., Liu, Q-H, Judd, B.A., Sigmund, C.D., Freedman, B.D., Koretzky, G.A. Differential requirements for SLP-76 domains in T cell development and function Immunity 15: 1011-26, 2001.

Collman, R.G., Yi, Y., Liu, Q-H, and Freedman, B.D. Chemokine signaling and HIV-1 fusion mediated by macrophage CXCR4: Implications for target cell tropism Journal of Leukocyte Biology 68: 318-23, 2000.

Freedman, B.D., Liu Q.H., Gaulton, G., Kotlikoff, M.I., Heschler, J., and Fleischmann, B.K. ATP-evoked Ca2+ transients and currents in murine thymocytes: Possible role for P2X receptors in death by neglect European Journal of Immunology 29: 1635-1646, 1999.

Masek, Katherine S. Fiore, Jim. Leitges, Michael. Yan, Shi-Fang. Freedman, Bruce D. Hunter, Christopher A. Host cell Ca2+ and protein kinase C regulate innate recognition of Toxoplasma gondii. Journal of Cell Science 119: 4565-73, 2006.

Gomez, Timothy S. McCarney, Sean D. Carrizosa, Esteban. Labno, Christine M. Comiskey, Erin O. Nolz, Jeffrey C. Zhu, Peimin. Freedman, Bruce D. Clark, Marcus R. Rawlings, David J. Billadeau, Daniel D. Burkhardt, Janis K. HS1 functions as an essential actin-regulatory adaptor protein at the immune synapse. Immunity 24: 741-52, 2006.

Wu, Jennifer N. Gheith, Shereen. Bezman, Natalie A. Liu, Qing-Hua. Fostel, Lindsey V. Swanson, Andrew M. Freedman, Bruce D. Koretzky, Gary A. Peterson, Erik J. Adhesion- and degranulation-promoting adapter protein is required for efficient thymocyte development and selection. Journal of Immunology 176: 6681-9, 2006.

Freedman, Bruce D. Mechanisms of calcium signaling and function in lymphocytes. [Review] [123 refs] Critical Reviews in Immunology 26: 97-111, 2006.

Liu, Xiaohong. Zhu, Peimin. Freedman, Bruce D. Multiple eicosanoid-activated nonselective cation channels regulate B-lymphocyte adhesion to integrin ligands. American Journal of Physiology - Cell Physiology 290: C873-82, 2006.

Nolz, Jeffrey C. Gomez, Timothy S. Zhu, Peimin. Li, Shuixing. Medeiros, Ricardo B. Shimizu, Yoji. Burkhardt, Janis K. Freedman, Bruce D. Billadeau, Daniel D. The WAVE2 complex regulates actin cytoskeletal reorganization and CRAC-mediated calcium entry during T cell activation. Current Biology 16: 24-34, 2006.

Liu, Qing-Hua. Liu, Xiaohong. Wen, Zhiyun. Hondowicz, Brian. King, Leslie. Monroe, John. Freedman, Bruce D. Distinct calcium channels regulate responses of primary B lymphocytes to B cell receptor engagement and mechanical stimuli. Journal of Immunology 174: 68-79, 2005.

Liu, Q H. Williams, D A. McManus, C. Baribaud, F. Doms, R W. Schols, D. De Clercq, E. Kotlikoff, M I. Collman, R G. Freedman, B D. HIV-1 gp120 and chemokines activate ion channels in primary macrophages through CCR5 and CXCR4 stimulation. Proceedings of the National Academy of Sciences of the United States of America 97: 4832-7, 2000.

Freedman, B D. Liu, Q H. Somersan, S. Kotlikoff, M I. Punt, J A. Receptor avidity and costimulation specify the intracellular Ca2+ signaling pattern in CD4(+)CD8(+) thymocytes. Journal of Experimental Medicine 190: 943-52, 1999.

Biswas, G. Adebanjo, O A. Freedman, B D. Anandatheerthavarada, H K. Vijayasarathy, C. Zaidi, M. Kotlikoff, M. Avadhani, N G. Retrograde Ca2+ signaling in C2C12 skeletal myocytes in response to mitochondrial genetic and metabolic stress: a novel mode of inter-organelle crosstalk. EMBO Journal 18: 522-33, 1999.

Adda, S. Fleischmann, B K. Freedman, B D. Yu, M. Hay, D W. Kotlikoff, M I. Expression and function of voltage-dependent potassium channel genes in human airway smooth muscle. Journal of Biological Chemistry 271: 13239-43, 1996.

Freedman, B D. Fleischmann, B K. Punt, J A. Gaulton, G. Hashimoto, Y. Kotlikoff, M I. 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: 22406-11, 1995.

Freedman, B D. Price, M A. Deutsch, C J. Evidence for voltage modulation of IL-2 production in mitogen-stimulated human peripheral blood lymphocytes. Journal of Immunology 149: 3784-94, 1992.

Nolz, Jeffrey C. Medeiros, Ricardo B. Mitchell, Jason S. Zhu, Peimin. Freedman, Bruce D. Shimizu, Yoji. Billadeau, Daniel D. WAVE2 regulates high-affinity integrin binding by recruiting vinculin and talin to the immunological synapse. Molecular & Cellular Biology 27: 5986-6000, 2007.

Babich Alexander, Li Shuixing, O'Connor Roddy S, Milone Michael C, Freedman Bruce D, Burkhardt Janis K F-actin polymerization and retrograde flow drive sustained PLC?1 signaling during T cell activation. The Journal of cell biology 197: 775-87, 2012.

Carrizosa Esteban, Gomez Timothy S, Labno Christine M, Klos Dehring Deborah A, Liu Xiaohong, Freedman Bruce D, Billadeau Daniel D, Burkhardt Janis K Hematopoietic lineage cell-specific protein 1 is recruited to the immunological synapse by IL-2-inducible T cell kinase and regulates phospholipase Cgamma1 Microcluster dynamics during T cell spreading. Journal of immunology (Baltimore, Md. : 1950) 183: 7352-61, 2009.

Zhu Peimin, Liu Xiaohong, Treml Laura S, Cancro Michael P, Freedman Bruce D Mechanism and regulatory function of CpG signaling via scavenger receptor B1 in primary B cells. The Journal of biological chemistry 284: 22878-87, 2009.

Shaffer Meredith H, Dupree Renell S, Zhu Peimin, Saotome Ichiko, Schmidt Richard F, McClatchey Andrea I, Freedman Bruce D, Burkhardt Janis K Ezrin and moesin function together to promote T cell activation. Journal of immunology (Baltimore, Md. : 1950) 182: 1021-32, 2009.

Masek K S, Zhu P, Freedman B D, Hunter C A Toxoplasma gondii induces changes in intracellular calcium in macrophages. Parasitology 134: 1973-9, 2007.

V.M.D. University of Pennsylvania, 1987

Ph.D. University of Pennsylvania, 1992

M.S. Pennsylvania State University, 1983

B.S. Dickinson College, 1980