Skip to content

David.Shepherd

Profile

Name: David Shepherd

Title: Associate Professor

Email: david.shepherd@umontana.edu

Phone: 406-243-2224

Office: SB 284

Background

After completing undergraduate work in Molecular Biology at Florida Institute of Technology, Dave Shepherd was trained as a cellular immunologist in the laboratory of Dr. Randolph J. Noelle at Dartmouth Medical School. He earned his Ph.D. in Toxicology at Oregon State University under the supervision of Dr. Nancy I. Kerkvliet. Following postdoctoral training in Molecular Toxicology with Dr. Mark Leid at OSU, he joined the faculty in the Department of Biomedical and Pharmaceutical Sciences at the University of Montana in 2002.

 

Research Statement

Many chemicals are known or suspected to cause deleterious effects on human health. Studies of pharmaceuticals and environmental contaminants indicate that the toxicity of many chemicals is mediated by a mechanism that involves or affects the immune system. Broadly speaking, chemicals can cause two different types of immune dysfunction: immune suppression, leading to an increased susceptibility to infectious diseases and cancer; and immune enhancement, leading to either autoimmune disease or allergy. While many studies indicate that exposure of humans and laboratory animals to chemicals can induce immune disorders, the mechanisms by which they alter immune function are largely unknown.

Dr. Shepherd's research program encompasses two somewhat distinct areas of immunotoxicology. The first focus of his laboratory centers on defining the role of the man-made environmental chemicals such as dioxins and PCBs on dendritic cells (DC), which are considered to be the "professional" antigen presenting cells in the immune system. His research is aimed at elucidating the mechanisms of immune suppression by these toxicants by addressing the role of Aryl hydrocarbon receptor activation in DC and the functional consequences of these alterations. The second area of investigation by this research group aims to define the efficacy and/or toxicity of natural chemicals in the immune system. Specifically, studies are being conducted to define the potential for several nutraceuticals such as notoginseng and thunder god vine to inhibit inflammation and boost adaptive immune responses. These studies utilize both in vitro and in vivo models of innate and adaptive immunity.

 

Publications

Rhule A.G., Rase B., Smith J.R., and SHEPHERD D.M. (2008). Toll-like receptor ligand-induced activation of murine DC2.4 cells is attenuated by Panax Notoginseng. J. Ethnopharm. 116: 179-186.

Rhule A.G., Navarro S., Smith J.R., and SHEPHERD D.M. (2006). Notoginseng Attenuates LPS-Induced Pro-Inflammatory Mediators in RAW264.7 cells. J. Ethnopharm 106: 121-128.

Leid M., Ishmael J.E., Avram D.A., SHEPHERD D.M., Fraulob V., and Dolle P. (2004). CTIP1 and CTIP2 are differentially expressed during mouse embryogenesis. Gene Exp Patterns 4: 733-739.

Funatake C.J., Dearstyne E.A., Steppan L.B., SHEPHERD D.M., Spanjaard E.S., Marshak-Rothstein A., and Kerkvliet N.I. (2004). Early consequences of 2,3,7,8-Tetrachlorodibenzo-p-dioxin exposure on the activation and survival of antigen-specific T cells. Toxicol. Sci. 82: 129-142.

Senawong T., Peterson V.J., Avram D., SHEPHERD D.M., Frye R.A., Minucci S., and Leid M. (2003) Involvement of the histone deacetylase SIRT1 in chicken ovalbumin upstream promoter transcription factor (COUP-TF)-interacting protein 2-mediated transcriptional repression. J. Biol. Chem. 278: 43041-43050.

Kerkvliet N.I., SHEPHERD D.M., and Baecher-Steppan L. (2002). T lymphocytes are direct, aryl hydrocarbon receptor (AhR)-dependent targets of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD): AhR expression in both CD4+ and CD8+ T cells is necessary for full suppression of a cytotoxic T lymphocyte response by TCDD. Toxicol. Appl. Pharmacol. 185: 146-152.

SHEPHERD D.M., Steppan L.B., Hedstrom O.R., and Kerkvliet N.I. (2001). Anti-CD40 treatment of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-exposed C57Bl/6 mice induces activation of antigen presenting cells yet fails to overcome TCDD-induced suppression of allograft immunity. Toxicol. Appl. Pharmacol. 170: 10-22.

SHEPHERD D.M., Dearstyne E.A., and Kerkvliet N.I. (2000). The effects of TCDD on the activation of ovalbumin (OVA)-specific DO11.10 transgenic CD4+T cells in adoptively transferred mice. Toxicol. Sci. 56: 340-350.

SHEPHERD D.M., and Kerkvliet N.I. (1999). Disruption of CD154:CD40 blocks generation of allograft immunity without affecting APC activation. J. Immunol. 163: 2470-2477.

Kerkvliet N.I., Baecher-Steppan L., SHEPHERD D.M., Oughton J.A., Vorderstrasse B.A., and DeKrey G.D. (1996). Inhibition of TC-1 cytokine production, effector cytotoxic T lymphocyte development and alloantibody production by 2,3,7,8-tetrachlorodibenzo-p-dioxin. J. Immunol. 157: 2310-2319.

Marshall L.M., SHEPHERD D.M., Ledbetter J.A., Aruffo A., and Noelle R.J. (1994). Signalling events during helper T cell-dependent B cell activation. I. Analysis of the signal transduction pathways triggered by activated helper T cell in resting B cells. J. Immunol. 152: 4816-4825.

Van den Eertwegh A.J., Noelle R.J., Roy M., SHEPHERD D.M., Aruffo A., Ledbetter J.A., Boersma J.M., and Claassen E. (1993). In vivo CD40-gp39 interactions are essential for thymus-dependent humoral immunity. I. In vivo expression of CD40 ligand, cytokines, and antibody production delineates sites of cognate T-B cell interactions. J. Exp. Med. 178: 1555-1565.

Foy T.M., SHEPHERD D.M., Durie F.H., Aruffo A., Ledbetter J.A., and Noelle R.J. (1993). In vivo CD40-gp39 interactions are essential for thymus-dependent humoral immunity. II. Prolonged suppression of the humoral immune response by an antibody to the ligand for CD40, gp39. J. Exp. Med. 178: 1567-1575.

Daum J.R., SHEPHERD D.M., and Noelle R.J. (1993). Immunotoxicology of cadmium and mercury on B lymphocytes-- I. Effects on lymphocyte function. Int. J. Immunopharmacol. 15: 383-394.

Noelle R.J., Marshall L.M., Roy M., SHEPHERD D.M., Stamenkovic I., Ledbetter J.A., Aruffo A., and Fell H.P. (1992). Role of contact and soluble factors in the growth and differentiation of B cells by helper T cells. Adv. Exp. Med. Biol. 323: 131-138.

Noelle R.J., SHEPHERD D.M., and Fell H.P. (1992). Cognate interaction between T helper cells and B cells. VII. Role of contact and lymphokines in the expression of germline and mature gamma 1 transcripts. J. Immunol. 149: 1164-1169.

Noelle R.J., Roy M., SHEPHERD D.M., Stamenkovic I., Ledbetter J.A., and Aruffo A. (1992). A 39-kDa protein on activated helper T cells binds CD40 and transduces the signal for cognate activation of B cells. Proc. Natl. Acad. Sci. U.S.A. 89: 6550-6554.

Noelle R.J., Daum J.R., Bartlett W.C., McCann J., and SHEPHERD D.M. (1991). Cognate interactions between helper T cells and B cells. V. Reconstitution of T helper cell function using purified plasma membranes from activated Th1 and Th2 T helper cells and lymphokines. J. Immunol. 146: 1118-1124.

SHEPHERD D.M., and Noelle R.J. (1991). The lack of memory B cells in immune bone marrow. Transplantation 52: 97-100.

Bartlett W.C., McCann J., SHEPHERD D.M., Roy M., and Noelle R.J. (1990). Cognate interactions between helper T cells and B cells. IV. Requirements for the expression of effector phase activity by helper T cells. J. Immunol. 145: 3956-3962.


The University of Montana-Missoula
The Department of Biomedical & Pharmaceutical Sciences
32 Campus Drive, Skaggs 395
Missoula, MT 59812-1552
Phone 406.243.4767 Fax: 406.243.5228
Email: biomed@umontana.edu

glqxz9283 sfy39587p06