Dr. Porcelli's laboratory focuses on the control of acquired immune responses by T cells, which are the master regulatory and key effector cells of host defense and immune tolerance. In broad terms, the research being pursued in the laboratory covers two interrelated areas. The first is to understand the role of regulatory T cells, with particular emphasis on the activities of a specialized T cell subset known as CD1d-restricted NKT cells. These T cells have the highly unusual property of responding to specific glycolipid antigens, which they recognize in combination with a specialized lipid antigen presenting molecule known as CD1d. The laboratory is studying the details of the cellular mechanisms that lead to the uptake and presentation of lipid antigens by CD1d, and is also using synthetic lipid antigens of NKT cells to determine how antigen structure controls the types of immune responses that are stimulated. The ability of lipid antigens that stimulate NKT cells to serve as adjuvants or immune modulators to control the outcome of disease processes is also being studied. The laboratory's second major research area is the study of T cell responses against pathogenic microorganisms, especially Mycobacterium tuberculosis. Work in this area has recently led to significant progress in understanding how mycobacteria block effective host T cell responses, and this information is now being used to further the design of more effective vaccines for prevention of tuberculosis. A major near term goal of this research is to broaden the understanding of how organisms like M. tuberculosis successfully evade eradication by the immune system. The major long term goal is to create a genetically modified live attenuated M. tuberculosis strain that will be safe and effective as a vaccine against tuberculosis.
1. Porcelli SA and Jacobs, WR Jr. Tuberculosis: unsealing the apoptotic envelope (News & Views). Nature Immunol. 9:1101-2 (2008).
2. Porcelli, SA. Tuberculosis: Shrewd survival strategy. Nature 454:702-3 (2008).
3. Im JS, Arora P, Bricard G, Molano A, Venkataswamy MM, Baine I, Jerud ES, Goldberg MF, Yu KOA, Ndonye RM, Howell AR, Yuan W, Cresswell P, Chang YT, Illarionov PA, Besra GS and Porcelli SA. Kinetics and cellular site of glycolipid loading control the outcome of Natural Killer T cell activation. Immunity 30:888-98 (2009).
4.Baena A, Porcelli SA. Evasion and subversion of antigen presentation by Mycobacterium tuberculosis. Tissue Antigens 74:189-204 (2009).
5. Venkataswamy MM, Baena A, Goldberg M, Bricard G, Im JS, Besra GS, Chan J, Jacobs Jr. WR and Porcelli SA. Enhancement of immunogenicity of M. bovis BCG by incorporation of NKT cell activating glycolipids. J Immunol. 183:1644-56 (2009).
6. Sweeney KA, Dao DN, Goldberg MF, Hsu T, Venkataswamy MM, Henao-Tamayo M, Ordway D, Sellers RS, Jain P, Chen B, Chen M, Kim J, Lukose R, Chan J, Orme IM, Porcelli SA and Jacobs WR Jr. A recombinant Mycobacterium smegmatis induces potent bactericidal immunity against Mycobacterium tuberculosis. Nature Medicine 17:1261-8 (2011).
7. Arora P, Venkataswamy MM, Baena A, Bricard G, Li Q, Veerapen N, Ndonye R, Park JJ, Lee JH, Seo KC, Howell AR, Chang YT, Illarionov PA, Besra GS, Chung SK and Porcelli SA. A rapid fluorescence-based assay for classification of iNKT cell activating glycolipids. J Am Chem Soc. 133:5198-201 (2011).
8. Venkataswamy MM, Goldberg MF, Baena A, Chan J, Jacobs WR Jr and Porcelli SA. In vitro culture medium influences the vaccine efficacy of Mycobacterium bovis BCG. Vaccine. 30:1038-49 (2012).
9. Arora P, Baena A, Yu KO, Saini NK, Kharkwal SS, Goldberg MF, Kunnath-Velayudhan S, Carreño LJ, Venkataswamy MM, Kim J, Lazar-Molnar E, Lauvau G, Chang YT, Liu Z, Bittman R, Al-Shamkhani A, Cox LR, Jervis PJ, Veerapen N, Besra GS, Porcelli SA. A single subset of dendritic cells controls the cytokine bias of natural killer T cell responses to diverse glycolipid antigens. Immunity. 40:105-16 (2014).
10. Singh M, Quispe-Tintaya W, Chandra D, Jahangir A, Venkataswamy MM, Ng TW, Sharma S, Carreño LJ, Porcelli SA*, Gravekamp C*. Direct incorporation of the NKT cell activator a-galactosylceramide improves efficacy and safety of a recombinant Listeria monocytogenes breast cancer vaccine. (*Joint senior/corresponding author). Br J Cancer. 2014 Nov 11;111(10):1945-54.
11. Arora, P., Porcelli, S. A. An Efficient and High Yield Method for Isolation of Mouse Dendritic Cell Subsets. J. Vis. Exp. e53824, doi:10.3791/53824 (2016).
Material in this section is provided by individual faculty members who are solely responsible for its accuracy and content.