Faculty Profile

Dr. Steven A. Porcelli, M.D.

Steven A. Porcelli, M.D.

Professor, Department of Microbiology & Immunology

Professor, Department of Medicine (Rheumatology)

Chair, Department of Microbiology & Immunology

Murray and Evelyne Weinstock Chair in Microbiology & Immunology

Scientific Director, Flow Cytometry Core Facility

Areas of Research: We study many aspects of T cell immunology and antigen presentation, with a particular interest in protective immunity to Mycobacterium tuberculosis. We also study novel vaccine adjuvants and immunotherapy of cancer.

Professional Interests

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, with strong emphasis on the development of immunotherapy for cancer. 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.

Selected Publications

1. Porcelli, SA. Tuberculosis: Shrewd survival strategy. Nature 454:702-3 (2008).

2. 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).

3. 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).

4.  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.

5.  Saini NK, Baena A, Ng TW, Venkataswamy MM, Kennedy SC, Kunnath-Velayudhan S, Carreno L, Xu J, Chan J, Larsen MH, Jacobs Jr. WR, Porcelli SA.  Suppression of autophagy and antigen presentation by Mycobacterium tuberculosis PE_PGRS47.  Nat Microbiol (9):16133 (2016). PMID: 27562263

6.  Johndrow CT, Goldberg, MF, Johnson AJ, Ng TW, Kunnath-Velayudhan, S, Lauvau G,  Gossel GH, Kadolsky UD, Yates AJ, Chan J, Jacobs, Jr. WR, Porcelli SA.  Suppression of Th1 Priming by TLR2 Agonists during Cutaneous Immunization Is Mediated by Recruited CCR2+ Monocytes.  J Immunol,.2018 Dec 15;201(12):3604-3616. doi: 10.4049/jimmunol.1801185. Epub 2018 Nov 19. PMID: 30455402.

7.  Johnson AJ, Kennedy SC, Lindestam Arlehamn CS, Goldberg MF, Saini NK, Xu J, Paul S, Hegde SS, Blanchard JS, Chan J, Jacobs WR Jr., Sette A, Porcelli SA.  Identification of Mycobacterial RplJ/L10 and RpsA/S1 Proteins as Novel Targets for CD4+ T Cells. Infect Immun. 2017;85(4), e01023-16.

8.  Kunnath-Velayudhan S, Goldberg MF, Saini NK, Johndrow CT, Ng TW, Johnson AJ, Xu J, Chan J, Jacobs WR Jr, Porcelli SA. Transcriptome Analysis of Mycobacteria-Specific CD4+ T Cells Identified by Activation-Induced Expression of CD154.  J Immunol. 2017 Oct 1;199(7):2596-2606. doi: 10.4049/jimmunol.1700654. Epub 2017 Aug 18.  PMID: 28821584

9.  Chennamadhavuni D, Saavedra-Avila NA, Carreño LJ, Guberman-Pfeffer MJ, Arora P, Yongqing T, Koay H-F, Godfrey DI, Keshipeddy S, Richardson SK, Sundararaj S, Lo JH, Wen X, Gascón JA, Yuan W, Rossjohn J, Le Nours J*, Porcelli SA* and Howell AR*. (*Joint corresponding authors).  Dual modifications of an α-galactosyl ceramide synergize to promote activation of human invariant natural killer T cells and stimulate anti-tumor immunity.  Cell Chemical Biology, S2451-9456(18)30073-4. (2018).  PMID: 29576533

10. Veerapen N, Kharkwal SS, Jervis P, Bhowruth V, Besra AK, North SJ, Haslam SM, Dell A, Hobrath J, Quaid PJ, Moynihan PJ, Cox LR, Kharkwal H, Zauderer M, Besra GS, Porcelli SA.  Photoactivable Glycolipid Antigens Generate Stable Conjugates with CD1d for Invariant Natural Killer T Cell Activation.  Bioconjug Chem. 2018 Sep 19;29(9):3161-3173. doi: 10.1021/acs.bioconjchem.8b00484. Epub 2018 Aug 23.  PMID: 30085659.

11.  Johnson AJ, Kennedy SC, Ng TW, Porcelli SA.  Identification of Novel Mycobacterial Targets for Murine CD4+ T-Cells by IFNγ ELISPOT.  Methods Mol Biol. 2018;1808:143-150. doi: 10.1007/978-1-4939-8567-8_12.   PMID:  29956180

12.  Kennedy SC, Johnson AJ, Bharrhan S, Lindestam Arlehamn CS, Xu J, Garforth SJ, Chan J, Jacobs WR Jr, Sette A, Almo SC, Porcelli SA.  Identification of Mycobacterial Ribosomal Proteins as Targets for CD4+ T Cells That Enhance Protective Immunity in Tuberculosis.  Infect Immun. 2018 Aug 22;86(9). pii: e00009-18. doi: 10.1128/IAI.00009-18. Print 2018 Sep.  PMID: 29891545. PMCID: PMC6105890

13.  Wang Y, Sedimbi S, Löfbom L, Singh AK, Porcelli SA, Cardell SL.  Unique invariant natural killer T cells promote intestinal polyps by suppressing TH1 immunity and promoting regulatory T cells.  Mucosal Immunol. 2018 Jan;11(1):131-143. doi: 10.1038/mi.2017.34. Epub 2017 Apr 12.  PMID: 28401935.  PMCID: PMC5638666

14.  Wang Y, Sedimbi SK, Löfbom L, Besra GS, Porcelli SA, Cardell SL.  Promotion or Suppression of Murine Intestinal Polyp Development by iNKT Cell Directed Immunotherapy Front Immunol. 2019 Mar 1;10:352. doi: 10.3389/fimmu.2019.00352. eCollection 2019.  PMID: 30881361

15.  Porcelli SA and Jacobs WR Jr.  Exacting Edward Jenner’s Revenge: Progress in TB Vaccine Development.  Science Translational Medicine, 2019 (in press).

 

 

 

 

 

 

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More Information About Dr. Steven Porcelli

Department of Microbiology and Immunology Faculty

Flow Cytometry Shared Resource

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Albert Einstein College of Medicine
Jack and Pearl Resnick Campus
1300 Morris Park Avenue
Forchheimer Building, Room 416
Bronx, NY 10461

Tel: 718.430.3228

Research Information