Ronald B. Smeltz, Ph.D.
Assistant Professor

Phone: (804) 828-8085 (office), (804) 826-3665 (lab)
Dept. Fax: (804) 828-9946
e-mail: rbsmeltz@vcu.edu

Address:
Department of Microbiology & Immunology
Virginia Commonwealth University
P.O. Box 980678
1217 East Marshall Street, Medical Sciences Building Room 323/325
Richmond, VA 23298-0678

Professional Experience

• B.S., 1993, The University of Akron
• M.S., 1995, The University of Akron
• Ph.D., 1999, Wayne State University
• Postdoctoral Fellow, 1999-2002, National Institutes of Health
• Research Scientist, 2002-2005, Aventis Pharmaceuticals

Recent Awards:

AD Williams research grant. “Maintaining protective immunity to Trypanosoma cruzi”.

Massey Cancer Center pilot grant program. “In vivo efficacy of IL-15/IL-15Ra complexes in abrogating immune tolerance to a breast carcinoma antigen”.

The Jeffress Memorial Trust.  “Synergy of inflammation and Interleukin-15 in development of effector cytotoxic T cells”.

Research Interests:

CD8⁺ cytotoxic T cells, or CTL, are critical to the body’s immune defense against infection, especially in the control of intracellular pathogens such as Trypanosoma cruzi (T. cruzi), the etiologic agent of Chagas disease.  Without T cells, immunodeficient hosts rapidly succumb to T. cruzi infection. Two primary means by which CTL control/eliminate intracellular pathogens are via secretion of cytokines (ie. gamma interferon, or IFN-g) and cytotoxicity (ie. killing).  Many of these T cell functions are regulated by T-bet, a transcription factor expressed primarily in T cells.  Hosts that do not express T-bet have an increased susceptibility to several intracellular infections (including Mycobacterium, the causative agent of tuberculosis), and we recently observed that T-bet is required for host survival after T. cruzi infection.

Using T. cruzi infection as our model, the first goal is to understand how T-bet regulates T cell responses to persistent infection.  T. cruzi poses significant challenges to the host immune system, including its ability to infect a wide range of host cells.  By understanding the role of T-bet in development and maintenance of T cell responses to an intracellular pathogen, we can improve our ability to enhance T cell responses with vaccination. 

A second area of interest is the interactions between T. cruzi-specific CTL and CD4⁺ T “helper” cells during infection.  These interactions are important for the survival, maintenance, and long-term function of CTL, and by identifying these interactions we can begin to understand what is required to generate (ie. via vaccination) stable populations of CTL that can provide long-term immunity to intracellular pathogens.

Several laboratory projects are available, which use state-of-the-art techniques such as CFSE dilution, MHC tetramers, confocal microscopy, in situ analysis, flow cytometry, and use of congenic T cells for long-term tracking of memory T cells in vivo.  Interested students should contact Dr. Smeltz to schedule a laboratory rotation.

Video (above): extensive parasitemia in Rag-2-deficient host, which has no T cells, on day 21 post-infection with the CL strain of T. cruzi.  The high numbers of T cruzi trypomastigotes, and their increased motility can be seen.

Images: Confocal analysis and immunofluorescent detection of T. cruzi amastigotes in skeletal muscle using serum from mice chronically infected with T. cruzi (Left: 100x magnification, Middle: 100x DIC image, Right: 10x magnification.  Blue = DAPI, Green = anti-mouse IgG FITC).                  

Selected Publications:

Guo, S., Lara, A.M., Manque, P. Buck, G.A., and Ronald B. Smeltz. T-bet is required for survival and immunity to the intracellular pathogen T. cruzi. 2008 (submitted).

Guo, S. and Smeltz, R.B. IL-15 synergizes with IL-12 to abrogate regulatory T cell-mediated suppression of CD8⁺ T cell responses in a T-bet-independent fashion. 2008 (submitted).

Smeltz, R.B.  Profound enhancement of the IL-12/IL-18 pathway of IFN-g secretion in human CD8+ memory T cell subsets via IL-15. The Journal of Immunology 178:4786-4792, 2007.

Smeltz, R.B., Chen, J., and E.M. Shevach.  TGF-b1 enhances the IFN-g-dependent, IL-12/STAT-4-independent pathway of Th1 cell differentiation. Immunology 114(4):484-92, 2005.

Smeltz, R.B., Chen, J., Erhardt, R., Shevach, E.M. Role of IFN-g in Th1 differentiation: IFN-g regulates IL-18Ra expression by preventing the negative effects of IL-4 and by inducing/maintaining IL-12Rb2 expression.  The Journal of Immunology 168:6165-6172, 2002.

Smeltz, R. B., Hu-Li, J., & Shevach, E. M. Regulation of interleukin-18 (IL-18) receptor expression during CD4⁺ T cell differentiation.  The Journal of Experimental Medicine 194(2):143-153, 2001.

Ortmann, R., Smeltz, R., Yap. G., Sher, A., & Shevach, E. M.  A heritable defect in IL-12-dependent signaling in B10.Q/J mice. I. In vitro analysis. The Journal of Immunology 166:5712-5719, 2001.

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Date Last Modified: 07/10/2008
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