Hao Shen, Ph.D.

Associate Professor of Microbiology

Office Address:
University of Pennsylvania School of Medicine
303C Johnson Pavilion
3610 Hamilton Walk
Philadelphia, PA 19104-6076

TEL 215-573-5259
LAB 215-898-6586;
Admin Asst: 215-573-2890
FAX 215-573-9068
hshen@mail.med.upenn.edu

RESEARCH SUMMARY

We are interested in understanding how the microbial virulence strategies affect the nature and magnitude of the host response and how the resulting immune response influences the course of infection. We use the intracellular bacterium Listeria monocytogenes as a model and employ a multidisciplinary approach that combines recent technical and conceptual advances in molecular genetics, microbial pathogenesis, cell biology and immunology. By genetic manipulation of both the microbe and the murine host, we are investigating how various immune effectors counter different microbial virulence factors. We are studying the mechanisms by which bacterial virulence factors down-modulate the immune response. We are also identifying different aspects of bacterial antigens that influence their ability to induce a T cell response and to serve as a protective target. Through these studies, we hope to identify new immune correlates of protection and understand the mechanisms that help establishing or disturbing the immunological memory.

We are also applying our expertise in cellular immunology and microbial pathogenesis to study emerging pathogens and bioterror agents. We are identifying T cell epitopes in Ebola and examining how the soluble glycoprotein (sGP) of Ebola may interfere with the ability of dendritic cells to prime T cell responses. We are studying the early immune response to the pulmonary form of anthrax infection and investigating the role of microbial phospholipases and hemolysin in modulating the host response. The long-term objective of our studies is to provide a platform for rational design of effective vaccines to combat today’s complex infectious diseases and potential bioterror threats.

SELECTED RECENT PUBLICATIONS

1. Northrop JK, Shen H.CD8+ T-cell memory: only the good ones last. Curr Opin Immunol. 2004;16(4):451-5.

2. Zenewicz LA, Skinner JA, Goldfine H, Shen H. Listeria monocytogenes Virulence Proteins Induce Surface Expression of Fas Ligand on T lymphocytes. Mol Microbiol 2004;51(5):1483-92.

3. Simmons G, Lee A, Rennekamp AJ, Fan X, Bates P, Shen H. Identification of murine T cell epitopes in Ebola virus nucleoprotein. Virology 2004;318(1):224-30.

4. Zheng SJ, Jiang J, Shen H. Chen YH. Reduced apoptosis and listeriosis in TRAIL-null mice. J. Immunol. 2004;173(9):5652-8.

5. Skinner JA, Reissinger A, Shen H, Yuk MH. Bordetella type III secretion and adenylate cyclase toxin synergize to drive dendritic cells into a semi-mature state. J. Immunol. 2004;173(3):1934-40.

6. Chua MM, MacNamara K, San Mateo LR, Shen H, Weiss SR. Effects of an epitope specific CD8+ T cell response on murine coronavirus CNS disease: protection from virus replication and antigen spread and selection of epitope escape mutants. J Virol 2004;78(3):1150-9).

7. Pearce EL, Shedlock DJ, Shen H. Functional Characterization of MHC Class II-Restricted CD8+CD4- and CD8-CD4- T Cell Responses to Infection in CD4-/- Mice. J Immunol. 2004;173(4):2494-9.

8. Pearce EL, Mullen AC, Martins GA, Krawczyk CM, Hutchins AS, Zediak VP, Banica M, DiCioccio CB, Gross DA, Mao C, Shen H, Cereb N, Yang SY, Lindsten T, Rossant J, Hunter CA, Reiner S. Control of effector CD8+ T cell function by the transcriptional factor Ecomesodermin. Science 2003 Nov 7;302(5647):1041-3.

9. Jiang J, Zenewicz LA, San Mateo LR, Lau LL, Shen H. Activation of antigen-specific CD8 T cells results in minimal killing of bystander bacteria. J Immunol. 2003;171(11):6032-8.

10. Jiang J, Lau LL, Shen H. Selective depletion of nonspecific T cells during the early stage of immune responses to infection. J Immunol. 2003 Oct 15;171(8):4352-8.

11. Shen H, Whitmire JK, Fan X, Shedlock DJ, Kaech SM, Ahmed R. A specific role for B cells in the generation of CD8 T cell memory by recombinant Listeria monocytogenes. J Immunol. 2003;170(3):1443-51.

12. Shedlock DJ, Whitmire JK, Tan J, MacDonald AS, Ahmed R, Shen H. Role of CD4 T cell help and costimulation in CD8 T cell responses during Listeria monocytogenes infection. J Immunol. 2003;170(4):2053-63.

13. Shedlock DJ, Shen H. Requirement for CD4 T cell help in generating
functional CD8 T cell memory. Science. 2003 Apr 11;300(5617):337-9.
[Abstract] [Full Text]

14. Zhong XP, Hainey EA, Olenchock BA, Jordan MS, Maltzman JS, Nichols KE, Shen H, Koretzky GA. Enhanced T cell responses due to diacylglycerol kinase zeta deficiency. Nat Immunol. 2003;4(9):882-90.

15. Troy AE, Shen H. Cutting edge: homeostatic proliferation of peripheral T lymphocytes is regulated by clonal competition. J Immunol. 2003;170(2):672-6.

16. Shen H, Miller JF, Fan X, Kolwyck D, Ahmed R, Harty JT. Compartmentalization of bacterial antigens: differential effects on priming of CD8 T cells and protective immunity. Cell. 1998 Feb 20;92(4):535-45.