Kar Muthumani, M.Sc., Ph.D.

Kar Muthumani, M.Sc., Ph.D.

  • Assistant Professor, Immunology, Microenvironment and Metastasis Program
  • Assistant Professor, Vaccine & Immunotherapy Center
  • 215-898-3710, kmuthumani@wistar.org

Kar Muthumani received his B.S., M.S. with honors and his Ph.D. from the Madurai Kamaraj University, India. He completed his postdoctoral training and Research Assistant Professorship at the University of Pennsylvania School of Medicine. He joined the Wistar Institute in 2016 as an Assistant Professor. His research interest is in the area of immune approaches to emerging infectious diseases and immune therapy approaches for the treatment cancer.  He has made several important contributions in this area including identifying a new strain of CHIKV virus, identification of host cellular targets of HIV accessory genes, new novel DNA vaccine approaches for HIV, CHIKV, RSV, Dengue, MERS and Zika among others.

Directing immune responses against emerging infectious diseases. We specialize in the development of novel DNA vaccines and therapeutics that target emerging infectious diseases. Using enhanced DNA technology, we have designed DNA vaccines that drive immune responses in prophylactic or therapeutic settings against Human Immunodeficiency Virus (HIV), Dengue (DV), Chikungunya virus (CHIKV), Middle Eastern Respiratory Syndrome (MERS) virus, and Zika Virus (ZV). We are characterizing the quantity and quality (i.e. B and T cell) of the immune responses induced or generated by these DNA plasmids in order to improve their ability to mediate virus neutralization and clearance.

Development of a novel plasmid-encoded IgG immunotherapeutic platform as a new tool for cancer treatment. We are developing a novel gene delivery system to produce anti-tumor and immunomodulatory antibodies in vivo for cancer treatment. This approach may be less expensive than existing anti-tumor monoclonal antibody delivery methods. Additionally, delivering these antibodies with DNA plasmid technology may increase duration of antibody expression in vivo and allowing for simple combination formulations in the absence of a host anti-vector immune response. Some targets of interest include the tumor antigens HER2 and PSMA, as well as the immune checkpoint proteins PD-1 and Lag3.

Selected Publications

1. Muthumani K*, Griffin B*, Agarwal S, Kudchodkar S, Reuschel E, Choi H, Kraynyak K, Duperret E, Keaton A, Chung C, Booth S, Racine T, Yan J, Morrow M, Jiang J, Lee B, Ramos S, Broderick K, Reed C, Khan A, Humeau L, Ugen K, Park Y, Maslow J, Sardesai N, Kim J, Kobinger G, Weiner DB. In vivo protection against ZIKV infection and pathogenesis through passive antibody transfer and active immunization with a prMEnv DNA vaccine. Npj Vaccines (2016) 1, 16021; doi:10.1038/ npjvaccines. 2016.21. (* Co-first authors).

2. Muthumani K, Block P, Flingai S, Muruganantham N, Chaaithanya IK, Tingey C, Wise M, Reuschel EL, Chung C, Muthumani A, Sarangan G, Srikanth P, Khan AS, Vijayachari P, Sardesai NY, Kim JJ, Ugen KE, Weiner DB (2016). Rapid and long-term immunity elicited by DNA encoded antibody prophylaxis and DNA vaccination against Chikungunya virus. The Journal of Infectious Diseases. 2016 Mar 21.

3. Muthumani K, Falzarano D, Reuschel EL, Tingey C, Flingai S, Villarreal DO, Wise M, Patel A, Izmirly A, Aljuaid A, Seliga AM, Soule G, Morrow M, Kraynyak KA, Khan AS, Scott DP, Feldmann F, LaCasse R, Meade-White K, Okumura A, Ugen KE, Sardesai NY, Kim JJ, Kobinger G, Feldmann H, Weiner DB (2015).  A synthetic consensus anti-spike protein DNA vaccine induces protective immunity against Middle East respiratory syndrome coronavirus in nonhuman primates. Science Translational Medicine. 19;7(301):301ra132.

4. Muthumani K, Flingai S, Wise M, Tingey C, Ugen KE, Weiner DB (2013). Optimized and enhanced DNA plasmid vector based in vivo construction of a neutralizing anti-HIV-1 envelope glycoprotein Fab. Human Vaccine and Immunotherapeutics. 9(10):2253-62.

5. Muthumani K, Shedlock DJ, Choo DK, Fagone P, Kawalekar OU, Goodman J, Bian CB, Ramanathan AA, Atman P, Tebas P, Chattergoon MA, Choo AY, and Weiner DB (2011). HIV-Mediated Phosphatidylinositol 3-Kinase/Serine-Threonine Kinase Activation in APCs Leads to Programmed Death-1 Ligand Upregulation and Suppression of HIV-Specific CD8 T Cells. Journal of Immunology 187(6): 2932-2943.

6. Mallilankaraman K, Shedlock DJ, Bao H, Kawalekar OU, Fagone P, Ramanathan AR, Ferraro B, Stabenow J, Vijayachari P, Sundaram SG, Muruganandam N, Sarangan G, Srikanth P, Khan AS, Lewis MG, Kim JJ, Sardesai NY, Muthumani K and Weiner DB (2011). A DNA vaccine against Chikungunya virus is protective in mice and induces neutralizing antibodies in mice and nonhuman primates. PLOS Neglected Tropical Diseases 11(5(1)): e928.

7. Muthumani K, Choo AY, Zong WX, Madesh M, Hwang DS, Premkumar A, Thieu KP, Emmanuel J, Kumar S, Thompson CB, Weiner DB (2006). The HIV-1 Vpr and glucocorticoid receptor complex is a gain-of-function interaction that prevents the nuclear localization of PARP-1. Nature Cell Biology 8(2): 170-179.

8. Muthumani K, Choo AY, Hwang DS, Premkumar A, Dayes NS, Harris C, Green DR, Wadsworth SA, Siekierka JJ, Weiner DB (2005). HIV-1 Nef-induced FasL induction and bystander killing requires p38 MAPK activation. Blood 106(6): 2059-2068.