Faculty

Todd A. Reinhart, ScD Professor, Assistant Chairman, and Director of IDM Graduate Programs E-mail: reinhar@pitt.edu Phone: 412-648-2341 Fax: 412-624-4873 Address: 606 Parran Hall 130 DeSoto Street Pittsburgh, PA 15261

Education

BA; Hamline University; 1986
ScD; Harvard University; School of Public Health, 1992

Research Interests

Role of chemokines in the pathogenesis of HIV-1 and SIV; basic biology and inhibition of chemokines; roles played by lymphatic endothelial cells in infectious diseases and vaccines; emerging infections and biodefense; vaccines for HIV-1, influenza, and cancer.

Research Summary

How HIV-1 causes AIDS remains incompletely understood. We are examining the contributions of the host response during infection to better understand the changes occurring in tissues, which should in turn help to develop strategies to reverse or overcome those changes associated with pathogenesis. Chemokines are small cytokines that recruit cells with the appropriate receptors into local environments, and they play multiple roles in the pathogenesis of HIV-1 and its nonhuman primate counterpart, simian immunodeficiency virus (SIV). Our efforts are heavily focused on understanding chemokines and their contributions to infectious diseases. Through gene expression profiling and histologic approaches, we are defining the effects of SIV on the networks of chemokines in lymphoid tissues, where much of the virus in the body is replicating. We are finding that those chemokines that change in expression are intimately involved in shaping local immune environments that can be advantageous to the virus.

Given the new roles we are defining for chemokines in HIV-1/SIV pathogenesis, we are also studying basic aspects of chemokine biology that could be responsible for their contributions to disease induction in infectious diseases as well as other chronic inflammatory diseases.

The lymphatics drain extracellular fluids and cells from peripheral tissues to lymph nodes and then ultimately into the blood stream. A new direction in the laboratory is focusing on the role that lymphatic endothelial cells (LECs) might play in inflammatory responses to infections, including those by HIV-1/SIV and Mycobacterium tuberculosis. Our studies to date indicate that there are multiple types of LECs in peripheral tissues and lymph nodes and they are exquisitely poised to sense and respond to pathogens.

In the areas of emerging infections and biodefense, we are participating in a new project that seeks to develop a DNA vaccine for seasonal and pandemic influenza and have participated in a collaborative project to determine the effects of anthrax toxins expressed by Bacillis anthracis on the immune and other organ systems.

Recent Publications

• Pegu, A., J.L. Flynn, and T.A. Reinhart. (2007) Afferent and Efferent Interfaces of Lymph Nodes Are Distinguished by Expression of Lymphatic Endothelial Markers and Chemokines. Lymphatic Research and Biology 5(2):91-104.

• Pegu, A., S. Qin, B.A. Fallert Junecko, R.E. Nisato, M.S. Pepper, and T.A. Reinhart. (2008) Human Lymphatic Endothelial Cells Express Multiple Functional Toll-like Receptors. Journal of Immunology 180(5):3399-3405.

• Aujla, S.J., M. Fei, D.A. Pociask, T.A. Reinhart, J. Edeal, K. Gaus, J.L. Kreindler, P.J. Dubin, M. Zheng, J.M. Pilewski, M.M. Myerburg, C.A. Mason, Y. Iwakura, and J. Kolls. (2008) IL-22 Mediates Mucosal Host Defense against Gram Negative Bacterial Pneumonia. Nature Medicine 14(3):275-81.

• Qin†, S., Y. Sui†, A. Soloff, B.A.F. Junecko, S.C. Watkins, D.E. Kirschner, J.E. Pease, M.A. Murphey-Corb, S. Barratt-Boyes, and T.A. Reinhart. (2008) Chemokine and Cytokine Mediated Loss of Regulatory T cells in Lymphoid Tissues during Pathogenic Simian Immunodeficiency Virus Infection. †These authors contributed equally to this work. Journal of Immunology 180:5530-5536.

• Rappocciolo, G.R., H.H. Hensler, M. Jais, T.A. Reinhart, A. Pegu, F.J. Jenkins, and C.R. Rinaldo. (2008) HHV-8 Infects and Replicates in Primary Cultures of Activated B Lymphocytes through DC-SIGN. Journal of Virology 82(10):4793-806.

• Verzijl, D., S,. Storelli, D. Scholten, L. Bosch, T.A. Reinhart, D.N. Streblow, C.P. Tensen, C.P. Fitzsimons, G.J.R. Zaman, J.E. Pease, I.J.P. de Esch, M.J. Smit, and R. Leurs. (2008) Non-competitive Antagonism and Inverse Agonism As A Mechanism of Action of Non-peptidergic Antagonists at Primate And Rodent CXCR3 Chemokine Receptors. The Journal of Pharmacology and Experimental Therapeutics 325(2):544-55.

• Muthuswamy, R., R. Mailliard, J.-J. Lee, T.A. Reinhart, D. Bartlett, and P. Kalinski. (2008) Dendritic Cells Maturing in Different Inflammatory Conditions Preferentially Interact with Effector or Regulatory T Cells. Cancer Research 68:5972-8.

• Reinhart, T.A., S. Qin, and Y. Sui. (2009) Multiple Roles for Chemokines in the Pathogenesis of SIV Infection. Current HIV Research 7:73-82.

Dr. Reinhart's Lab

L – R: Dr. Todd Reinhart, Carissa Flores, Charis Tjoeng, Beth Junecko, Cynthia Klamar, Shulin Qin