Research being conducted in my laboratory is in the general areas of immunopharmacology and immunotoxicology and encompasses a number of extramurally funded projects. A major emphasis of all of the projects is the elucidation of the molecular mechanisms for impairment of signal transduction cascades and gene expression during lymphocyte activation by drugs and chemicals. One major research focus is to characterize the mechanism for immune modulation by cannabinoid compounds. This effort has led to the first characterization of cannabinoid receptors within the immune system. Current goals include elucidation of signal transduction events initiated through as well as independently of cannabinoid receptors, including the peroxisome proliferator activated receptor (PPARy), leading to aberrant cytokine gene expression by T lymphocytes. A second major research focus is the characterization of the molecular mechanism responsible for altered B cell function produced by halogenated aromatic hydrocarbons, including dioxins and polychlorinated biphenols. This research, which resulted in the first characterization of the aryl hydrocarbon (AH) receptor and aryl hydrocarbon receptor nuclear translocator in B cells, has lead us to test the hypothesis that dioxin and dioxin-like compounds suppress antibody responses by impairing B cell differentiation in an AH receptor-dependent manner. A third area of research concerns studies aimed at characterizing the role of cytokines expression patterns in airway remodeling induced by chemical and protein respiratory allergens as well as by respiratory pathogens.

Selected Achievements since 2001

Appointments
Director, Center for Integrative Toxicology, Michigan State University, 2004-present

Editorial Boards
Associate Editor, Journal of Pharmacology and Experimental Therapeutics
Editorial board for Toxicological Sciences
Editorial board for International Immunopharmacology
Editorial Board for Journal of Immunotoxicology
Founding Member, Editorial Board for Nonlinearity in Biology, Toxicology and Medicine

Scientific Societies
Society of Toxicology: Member of Council 2004-2007, Treasurer 2005-2007
Society on Neuroimmune Pharmacology, Council, Chair of Membership Committee,
American Association of Immunologists
American Society of Pharmacology and Experimental Therapeutics
International Cannabinoid Research Society

Scientific Advisory Committees
National Academy of Sciences Committee to Review the Health Effects in Vietnam Veterans of Exposure to Herbicides
U.S. Environmental Protection Agency (US-EPA) Science Advisory Board for the Dioxin Reassessment Review
National Academy of Sciences Committee to review EPA’s Exposure and Human Health Reassessment of TCDD and Related Compounds

Other Service
Board of Trustees, Vice Chair of Communication Committee, International Life Sciences Institute, Health and Environmental Sciences Institute, 2003-present
Member for the Environmental Protection Agency Science Review Panel for Health Research
Member of Peer Review Committee, Experimental Toxicology Division, NHEERL, US-EPA, Research Triangle Park, NC
Member of Peer Review Committee for the American Chemistry Council on the Susceptibility of the Developing Immune System to Immunosuppressive Agents
Member, NIH Clinical Sciences Special Emphasis Panel (ZRG1-ALTX-4) 1999-2004
Ad Hoc Reviewer, NIH Hepatobiliary Pathophysiology Study Section; NTP Contract for Immunotoxicology; NIDA Sciences Special Emphasis Panel ZRG4-SSS-G 03

Selected Samples of Publications Since 2001

Jan, T.R., and Kaminski, N.E.: Role of mitogen-activated protein kinases in the differential regulation of interleukin-2 by cannabinol. J. Leuk. Biol. 69:841-849, 2001.

Jan, T.R., Rao, G.K. and Kaminski, N.E.,: Cannabinol enhancement of interleukin (IL)-2 by T cells is associated with an increase in IL-2 distal NF-AT activity. Mol. Pharmacol. 61:446-454, 2002.

Suh, J., Jeon, Y.J., Kim, H.M., Kang, J.S., Kaminski, N.E., Yang, K.H.: Aryl hydrocarbon receptor-dependent inhibition of AP-1 activity by 2,3,7,8-tetrachlorodibenzo-p-dioxin-mediated B cell dysfunction. Toxicol. Appl. Pharmacol. 181: 116-123, 2002.

Suh, J., Kang, J., Yang, K.H., and Kaminski, N.E.: Antagonism of aryl hydrocarbon receptor-dependent induction of CYP1A1 and inhibition of IgM expression by di-ortho-substituted polychlorinated biphenyls. Toxicol. Appl. Pharmacol. 187:11-21, 2003

Jan, T.R., Farraj, A.K., Harkema, J.R., and Kaminski, N.E.: Attenuation of the ovalbumin-induced allergic airway response by cannabinoid treatments in A/J mice. Toxicol. Appl. Pharmacol. 188:24-35, 2003.

Li, J., Kaminski, N.E., and Wang, D.H.: Anandamide-induced depressor effect in spontaneously hypertensive rats: Role of the vanilloid receptor (VR1). Hypertension 41:757-6, 2003.

Crawford R.B., Sulentic, C.E.W., Yoo, B.S., and Kaminski, N.E.: 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) alters the regulation and posttranslational modification of p27kip1 in lipopolyssacharide-activated B cells. Toxicol. Sci. 75: 333-342, 2003.

Farraj, A.K., Harkema, J.R., Jan, T.R., and Kaminski, N.E.: Immune responses in the lung and local lymph node of A/J mice to intranasal sensitization and challenge with adjuvant-free ovalbumin. Toxicol. Pathol. 31:432-447, 2003.

Faubert Kaplan, B.L., Rockwell, C.E. and Kaminski, N.E.::Evidence for cannabinoid receptor-dependent and –independent mechanisms of action in leukocytes. J. Pharmacol. Exp. Ther. 306:1077-1085, 2003.

Faubert Kaplan, B.L. and Kaminski, N.E.: Inhibition of ERK MAPK by Cannabinoids in PMA/Io-Stimulated Mouse Splenocytes. Intl. Immunopharmacol. 3/10-11:1503-1510, 2003.

McKarns, S.C., Letterio, J.J. and Kaminski, N.E.: Concentration-Dependent Bifunctional Effect of TGF-b1 on Immunoglobulin Production: A Role for Smad3 in IgA Production In Vitro. Intl. Immunopharmacol.3:1761-1774, 2003.

Yoo, B.S., Boverhoff, D.R., Shnaider, D., Crawford R.B., Zacharewski, T.R. and Kaminski, N.E.: 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) alters the regulation of Pax5 in lipopolysaccharide –activated B cells. Toxicol. Sci. 77 (2):272-279, 2004.

Sulentic, C.E.W., Zhang, W., Na, Y.J and Kaminski, N.E.: 2,3,7,8-tetrachlorodibenzo-p-dioxin, an exogenous modulator of the 3’a immunoglobulin heavy chain enhancer. J. Pharmacol. Exp. Ther. 309:71-78, 2004.

McKarns, S.C., Schwartz, R.H. and Kaminski, N.E.: Smad3 is essential for TGF-b1 to suppress IL-2 production and T cell receptor-induced proliferation, but not IL-2-induced proliferation. J. Immunol. 172:4275-4284, 2004.

Farraj, A.K., Harkema, J.R., and Kaminski, N.E.: Allergic rhinitis induced by intranasal sensitization and challenge with trimellitic anhydride but not dinitrochlorobenzene or oxazolone in A/J mice. Toxicol. Sci. 79:315-325, 2004.

Wang, Y., Kaminski, N.E. and Wang, D.H.: VR1-mediated depressor effects during high-salt intake role of anandamide. Hypertension 46: 986-991, 2005.

Rao, G.R., and Kaminski, N.E.: Induction of intracellular calcium elevation by D9-Tetrahydrocannabinol in T cells involves TRPC1 channels. J. Leuk. Biol. 79(1): 202-213, 2006.

Rao, G.R. and Kaminski, N.E.: Cannabinoid-mediated elevation of intracellular
calcium: A structure-activity relationship J. Pharmacol. Exp. Therap. 317(2):820-829, 2006.

Farraj, A.K., Harkema, J.R., and Kaminski, N.E.: Topical application versus intranasal
instillation: A qualitative comparison of the effect of the route of sensitization on Trimellitic Anhydride induced allergic rhinitis in A/J Mice. Toxicol. Sci.92:321-328, 2006.

Rao, G.K., Zhang, W. and Kaminski, N.E.: Cannabinoid receptor-mediated regulation of intracellular calcium by D9-tetrahydrocannabinol in T cells. J. Leuk. Biol. 75:884-882, 2004.

Sulentic, C.E.W., Kang, J.S., Na, Y.J. and Kaminski, N.E.: Interactions at a dioxin responsive Element (DRE) and an overlapping kB site within the hs4 domain of the 3’a immunoglobulin heavy chain enhancer. Toxicology. 200: 235-246, 2004.

Rockwell, C.E. and Kaminski, N.E.: A cyclooxygenase metabolite of anandamide causes inhibition of interleukin-2 secretion in murine splenocytes. J. Pharmacol. Exp. Therap. 311: 683-690, 2004.

Boverhof, D.R., Tam, E., Harney, A.S., Crawford, R.B., Kaminski, N.E and Zacharewski, T.R.: 2,3,7,8-tetrachlorodibenzo-p-dioxin induces suppressor of cytokine signaling-2 in murine B-cells. Mol. Pharmacol. 66(6): 1662-1667, 2004.

Kaplan, B.L.F., Ouyang, Y., Rockwell, C.E., Rao, G.K. and Kaminski, N.E.: 2-Arachidonoyl-glycerol suppresses interferon-gamma production in phorbol ester/ionomycin-activated mouse splenocytes independent of CB1 or CB2. J. Leuk. Biol. 77(6):966-974, 2005.

Kaplan, B.L.F., Ouyang, Y., Herring, A., Yea, S.S., Razdan, R. and Kaminski, N.E.: Inhibition of leukocyte function and interleukin-2 (IL-2) gene expression by 2-methylarachidonyl- (2’-fluoroethyl) amide, a stable congener of the endogenous cannabinoid receptor ligand anandamine. Toxicol. Appl. Pharmacol. 205(2): 107-115, 2005.

Wang, Y., Kaminski, N.E. and Wang, D.H.: VR1-mediated depressor effects during high-salt intake role of anandamide. Hypertension 46: 986-991, 2005.

Rao, G.R., and Kaminski, N.E.: Induction of intracellular calcium elevation by D9-Tetrahydrocannabinol in T cells involves TRPC1 channels. J. Leuk. Biol. 79(1): 202-213, 2006.

Rao, G.R. and Kaminski, N.E.: Cannabinoid-mediated elevation of intracellular calcium: A structure-activity relationship J. Pharmacol. Exper. Therap. 317(2):820-829, 2006.

Farraj, A.K., Harkema, J.R., and Kaminski, N.E.: Topical application versus intranasal
instillation: A qualitative comparison of the effect of the route of sensitization on Trimellitic Anhydride induced allergic rhinitis in A/J Mice. Toxicol. Sci.92:321-328, 2006.

Rockwell, C.E. and Kaminski, N.E.: Interleukin-2 suppression by 2-arachidonyl glycerol is mediated through peroxisome proliferator activated receptor gamma independently of cannabinoid receptors 1 and 2. Mol. Pharmacol. 70:101-111, 2006.

Buchweitz, J.P., Harkema, J.R. and Kaminski, N.E.: Time-dependent Airway Epithelial and Inflammatory Cell Responses Induced By Influenza Virus A/PR/8/34 In C57BL/6 Mice. Toxicol. Pathol. (in press).