Ronald B. Smeltz, Ph.D.
Assistant Professor

Phone: (804) 828-8085
Dept. Fax: (804) 828-9946
e-mail: rbsmeltz@vcu.edu

Address:
Department of Microbiology & Immunology
Virginia Commonwealth University
Molecular Medicine Research Building, Room 4044
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:

2009 American Association of Immunologists (AAI) Junior Faculty Award

2007 American Association of Immunologists (AAI) Junior Faculty Award

Research Interests:

T cells (including CD4⁺ T helper cells and CD8⁺ cytotoxic T cells), cytokines (including IFN-g, IL-17), transcription factors (including T-bet), T cell immunity to infection.

Research Summary:

T cells 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 T cells control/eliminate intracellular pathogens are via secretion of cytokines (ie. gamma interferon, or IFN-g) and cytotoxicity (ie. killing).  Many anti-microbial T cell functions are regulated by T-bet, a T-box family transcription factor expressed primarily in T cells.  Defects and polymorphisms in T-bet expression are linked to an increased susceptibility to intracellular infections including Mycobacterium (causative agent of tuberculosis), Salmonella, and HSV. We recently reported that T-bet is required for host protection against T. cruzi¹ Using T. cruzi infection as our model, our laboratory's mission is to understand the molecular basis of T cell responses to infection. Information gained from such studies will improve future efforts aimed at enhancing T cell immunity to infections through vaccination.

Specific projects:

1. T-bet-dependent regulation of CD4⁺ Th17 cell differentiation

2. Transcriptional regulation of CD8⁺ T cell responses to infection

My laboratory uses state-of-the-art techniques such as MHC tetramers, retroviral-mediated gene delivery, flow cytometry, CFSE dilution and use of congenic T cells for long-term tracking of antigen-specific T cells in vivo, confocal microscopy, and in situ analysis.  Interested students should contact Dr. Smeltz to schedule a laboratory rotation

Laboratory members (above): Ronald Smeltz (left), Siqi Guo (center), and Dustin Cobb (right)

 

Movie (above): extensive parasitemia in Rag-2-deficient host, which has no T cells, on day 21 post-infection with T. cruzi. High numbers of T cruzi trypomastigotes can be seen.  Courtesy of Ana Maria Lara and laboratory of Dr. Gregory Buck.

                       

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

Selected Publications:

1. Cobb, DA, Guo, S., Lara, AM, Manque, P, Buck, G, and Smeltz, R.B.  T-bet-dependent regulation of CD8⁺ T cell expansion during experimental Trypanosoma cruzi infection. Immunology, 2009 (in press).

2. Guo, S., Cobb, DA, and Smeltz, R.B. T-bet inhibits the in vivo differentiation of parasite-specific CD4⁺ Th17 cells in a T cell-intrinsic manner. The Journal of Immunology 182:6179–6186, 2009.

3. 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.

4. 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. 

(Additional publications can be found on Pub Med)

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Date Last Modified: 09/03/2009
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