Medical Microbiology and Immunology : Z. Kevin Pan, M.D., Ph.D.

Professor
Director of IIT Graduate Track (Infection, Immunity & Transplantation)

Molecular mechanisms of host-pathogen interactions

E-mail Address: kevin.pan@utoledo.edu
Office Phone Number: (419) 383-5466
Fax:  (419) 383-3002

- The structural features of the Toll-like receptors (TLRs) and the structural changes by which binding of a microbial ligand to the receptor leads to intracellular signaling cascades.

- Involvement of TLRs for microbial pathogens in several inflammatory diseases, including asthma and acute lung injury.

- G protein-coupled chemoattrant receptors function and biology.

Dr. Pan's laboratory is interested in molecular mechanisms by which cells use the innate immune system to detect microbes and initiate defensive inflammatory responses. A major focus of the work is the mechanisms that underlie receptor-mediated signaling events leading to activation of inflammatory cells.

Dr. Pan received his M.D. and Ph.D. in 1991 at the Shanghai Medical University II. After postdoctoral work at The Scripps Research Institute (La Jolla, CA) for immunology, he was appointed to the faculty of the Molecular and Experimental Medicine Department at The Scripps Research Institute in 2000. Dr. Pan joined the Department of Medical Microbiology and Immunology in 2003 and he is currently an Adjunct Associate Professor in the Department of Molecular and Experimental Medicine at The Scripps Research Institute.

Representative Publications:

Mukherjee, S, Chen, L-Y, Papadimos, TJ, Zuraw BL, and Pan, ZK  (2009)  LPS driven Th2 cytokine production in monocytes/macrophages is regulated by MyD88 and TRAM.  J. Biol. Chem.
In Press.
 
Su S, Li Y, Luo Y, Sheng Y, Su Y, Padia RN, Pan ZK, Dong Z, Huang S.  (2009)  Proteinase-activated receptor 2 expression in breast cancer and its role in breast cancer cell migration.
Oncogene.   In Press.

Chen, L-Y, Pan, ZK  (2009) Synergistic Activation of Leukocytes by Bacterial Chemoattractants:Potential Drug Targets.     Endocr Metab Immune Disord Drug Targets.  In Press .
 
Bohman, KD, Papadimos, TJ, Gottwald, LD, and Pan, ZK (2009) Perniosis (chilblains) masquerading as CA-MRSA: a case report. CASES J. 6500, //casesjournal.com/casesjournal/article/view/6500

XS Huang, L-Y Chen, AM Doerner, WW Pan, S Huang, TJ Papadimos, and ZK Pan.  (2009) An atypical protein kinase C (PKCzeta) plays a critical role in LPS-activated NF-kappaB in human peripheral blood monocytes and macrophages.  J. Immunol. May 182(9):5810-5.

L-Y Chen, WW Pan, M. Chen, J-D Li, W Liu, G Chen, S Huang, TJ Papadimos, and ZK Pan.  (2009) Synergistic induction of inflammation by bacterial products LPS and fMLP: An importanat microbial pathogenic mechanism.  J. Immunol.  182(4):2518-2524. 

Neeson, P, Pan, ZK, and Paterson, Y   (2009) Listeriolysin O is an improved protein carrier for lymphoma immunoglobulin idiotype and provides systemic protection against 38C13 lymphoma.  Cancer Immunol. Immunother. 57(4):493-505.

Mahanivong C, Chen HM, Yee SW, Pan ZK, Dong Z and Huang S.  (2008) Protein kinase C-CARMA3 signaling axis links Ras to NF-kB for lysophosphatidic acid-induced urokinase plasminogen activator expression in ovarian cancer cells.  Oncogene.  27(9):1273-1280.

Souders NC, Sewell DA, Pan ZK, Hussain SF, Rodriguez A, Wallecha A, Paterson Y.  (2007) Listeria-based vaccines can overcome tolerance by expanding low avidity CD8+ T cells capable of eradicating a solid tumor in a transgenic mouse model of cancer.  Cancer Immun. Feb 6; 7:2.

He R, Shepard LW, Chen J, Pan Z.K, Ye RD. (2006) Serum amyloid A is an endogenous ligand that differentially induces IL-12 and IL-23.  J Immunol. 177(6):4072-4079.

Papadimos TJ, Smith L, Mukherjee S, Popovic D, Chen LY, Pan Z.K. (2006)  A lack of toll-like receptor 4 expression variability in the immediate preoperative period: a pilot study of elective surgical patients. Eur J Anaesthesiol.   23(10):892-3.

Pirbhai M, Dong F, Zhong Y, Pan ZK, Zhong G.  (2006) The secreted protease factor CPAF is responsible for degrading pro-apoptotic BH3-only proteins in Chlamydia trachomatis-infected cells.  J Biol Chem.   281(42):31495-501.

Bian D, Mahanivong C, Yu J, Frisch SM, Pan ZK, Ye RD, Huang S. (2006)  The G(12/13)-RhoA signaling pathway contributes to efficient lysophosphatidic acid-stimulated cell migration. Oncogene.   25:2234-2244.

Chen L-Y, Doerner A., Lehmann P.F., Huang S., Zhong G., and Pan ZK (2005) A Novel Protein Kinase C  Is a Signaling Component Downstream of GTPase RhoA and Mediates Chemoattractant-induced NF-kB Activation in Human Blood Monocytes.  J. Biol. Chem. 280:22497-22501.

Joko H., Lim, J.H., Chen, L-F., Xu, H., Trompouki, E., Pan, Z.K., Mosialos, G., Li, J. (2004) NF-kB is essential for induction of CYLD, the negative regulator of NF-kB: evidence for a novel inducible auto-regulatory feedback pathway. J. Biol. Chem.  279:36171-36174.

Chen, L-Y., Ptasznik, A., and Pan, Z.K. (2004) RhoA and Rac1 signals in fMLP-induced NF-kB activation in human blood monocytes. Biochem. Biophys. Res. Commun. 319:629-635.

Bian, D., Su, S., Mahanivong, C., Cheng, R.K., Han, Q., Pan, Z.K., Sun, P., and Huang, S. (2004) Lysophosphatidic acid stimulates ovarian cancer cell migration via a Ras-MEK kinase 1 pathway. Cancer Res., 64:4209-4217.

Chen, L-Y., Zuraw, B.L., Ye, R.D. and Pan, Z.K. (2004) A Rho exchange factor mediates fMet-Leu-Phe-induced NF-kB activation in human peripheral blood monocytes. J. Biol. Chem. 279:7208-7212.

Su, H., McClarty, G., Dong, F., Hatch, G., Pan, Z., and Zhong, G. (2004) Activation of Raf/MEK/ERK/cPLA2 signaling pathway is essential for chlamydial acquisition of host glycerophospholipids. J. Biol. Chem. 279:9409-9416.

Pan, Z.K. (2004) Toll-like receptors (TLRs) and TLR-mediated signaling: more questions than answers. Am. J. Physiol. 286:L918-920.

Chen, L-Y., Zuraw, B.L., Zhao, M., Liu, F-T., Huang, S., and Pan, Z.K. (2003) Involvement of protein tyrosine kinase in Toll-like receptor 4 (TLR4)-mediated NF-kB activation in human peripheral blood monocytes. Am. J. Physiol., 284:L607-L613.

Chen, L-Y., Zuraw, B.L., Liu, F-T., Huang S., and Pan, Z.K. (2002) IL-1 Receptor-associated kinase and GTPase RhoA signal molecules are required for bacterial lipopolysaccharide (LPS)-induced cytokine gene transcription. J. Immunol., 169:3934-3939.

Ptasznik, A., Chinta, S., Costa, M.A., Kalota, A., Swider, C.R., Katz, B.A., Demir, G., Pan, Z.K., and Gewirtz, A.M. (2002) Crosstalk between BCR/ABL oncoprotein and CXCR4 signaling through a Src family kinase in human leukemia cells. J. Exp. Med., 196:667-678.

Han, Q., Leng, J., Bian, D., Mahanivong, C., Carpenter K.A., Pan, Z.K., Han, J., and Huang S. (2002) Rac1-MKK3-p38-MAPKAKPK2 pathway promotes urokinase plaminogen activator mRNA stability in invasive breast cancer cells. J. Biol. Chem., 277:48379-48385.

Christiansen, S., Eddleston, J., Woessner, K., Chambers, S., Ye, R.D., Pan, Z.K., and Zuraw, B.L. (2002) Upregulation of functional B1 bradykinin receptors in allergic airway inflammation. J. Immunol., 169:2054-2060.

Chen, S., Bacon, K.B., Garcia, G., Liao, R., Pan, Z.K., Sullivan, S.K., Nakano, H., Matsuzawa, A., Brinkmann, V., Feng, L. (2001) FTY720, a novel transplantation drug, modulates lymphocyte migratory responses to chemokines. Transplant. Proc., 33:3057-63.

Chen, J., Bakersville, C., Han, Q., Pan, Z.K., and Huang, S. (2001) av integrin, p38 mitogen-activated protein kinase and urokinase plasminogen activator are functionally linked in invasive breast cancer cells. J. Biol. Chem., 276:47901-47905.

Ratajczak, J., Majka, M., Kijowski, J., Baj, M., Pan, Z.K., Marquez, L.A., Janowska-Wieczorek, A., Ratajczak, M.Z. (2001) Biological significance of MAPK, AKT and JAK-STAT protein activation by various erythropoietic factors in normal human early erythroid cells. Br. J. Haematol., 115:195-204.

Huang, S., Chen, L-Y., Zuraw, B.L., Ye, R.D., and Pan, Z.K. (2001) Chemoattractant-stimulated NF-kB activation is dependent on the low molecular weight GTPase RhoA. J. Biol. Chem., 276:40977-40981.

Pan, Z.K., Chen, L.Y., Cochrane, C.G., Zuraw, B.L. (2000) fMet-Leu-Phe stimulates proinflammatory cytokine gene expression in Human Peripheral Blood Monocytes: the Role of Phosphatidylinositol 3-kinase. J. Immunol., 164:404-411.

Huang, S., New, L., Pan, Z.K., Han, J., Nemerow, G.R. (2000) Urokinase Plasminogen Activator/Urokinase-specific surface receptor expression and matrix invasion by breast cancer cells requires constitutive p38a mitogen-activated protein kinase activity. J. Biol. Chem., 275:12266-12272.

Majka, M., Janowska-Wieczorek, A., Ratajczak, J., Kowalska, M.A., Vilaire, G., Pan, Z.K., Honczarenko, M., Marquez, L.A., Poncz, M., Ratajczak, M.Z. (2000) Stromal-derived factor 1 and thrombopoietin regulate distinct aspects of human megakaryopoiesis. Blood, 96:4142-51.

Hsu, D.K., Yang, R-Y., Pan, Z.K., Salomon, D.R., Fung-Leung, W-P., Liu, F.T. (2000) Targeted disruption of the galectin-3 gene results in attenuated peritoneal inflammatory responses. Am. J. Pathol., 156:1073-1083.

Pan, Z.K., Christiansen, S., Ptasznik, A., Zuraw, B.L. (1999) Requirement of PI 3-kinase activity for bradykinin stimulation of NF-B activation in cultured human epithelial cells. J. Biol. Chem., 274:9918-9922.

Pan, Z.K. (1998) Anaphylatoxin C5a and C3a Induce NF-B activation in Human Peripheral Blood Monocytes. Biochem. Biophys. Acta., 1443:90-98.

Pan, Z.K., Ye, R.D., Christiansen, S.C., Jagels, M.K., Bokoch, G.M., Zuraw, B.L. (1998) Role of the Rho GTPase in bradykinin stimulated NF-B activation and interleukin-1 gene expression in cultured human epithelial cells. J. Immunol., 160:3038-3045.

Browning, D.D., Pan, Z.K., Prossnitz, E.R., Ye, R.D. (1997) Cell type and developmental stage-specific activation of NF-B by fMet-Leu-Phe in myeloid cells. J. Biol. Chem., 272:7995-8001.

Quehenberger, O., Pan, Z.K., Prossnitz, E.R., Cochrance, C.G., Ye, R.D. (1997) Identification of an N-formyl peptide receptor ligand binding domain by a gain-of-function approach. Biochem. Biophys. Res. Commun., 238(2):377-381.

Roglic, A., Prossnitz, E.R., Pan, Z.K., Ye, R.D. (1996) cDNA cloning of a novel G protein-coupled receptor with a large extracellular loop structure. Biochem. Biophys. Acta., 1305:39-43.