Karuppiah Muthumani

faculty photo
Research Assistant Professor of Pathology and Laboratory Medicine
Department: Pathology and Laboratory Medicine

Contact information
Dept of Pathology and Lab. Medicine
505 Stellar-Chance Labs
422 Curie Blvd
Philadelphia, PA 19104
Office: 215-746-8217
Fax: 215-573-9436
B.S. (Biology)
Madurai-Kamaraj University, India, 1985.
M.S. (Biology)
Madurai-Kamaraj University, India, 1989.
Ph.D. (Biology)
Madurai-Kamaraj University, India, 1996.
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Description of Research Expertise

DNA vaccine and post-exposure prophylaxis development for emerging infectious diseases

Effective vaccines are still needed to combat a number of deadly diseases. Over the past 25 years, multiple vaccine platforms have been developed to induce protective viral-specific immunity. DNA vaccination is one such platform. The platform’s safety has been well documented in numerous clinical protocols clinic, showing no adverse effects. Furthermore, the simplicity of DNA plasmid engineering and production as compared to live attenuated and killed viral vaccines makes it an attractive technology. DNA vaccines are also very stable and, therefore, ideal candidates for distribution in resource-poor communities where serious infectious pathogens remain endemic. It is anticipated that this effort will yield synthetic DNA constructs that can be administered alone as a prophylactic vaccine or in combination with biological monoclonal antibodies (mAbs) to offer broad, rapid, and sustained protection against emerging infections.

1) Develop and characterize the efficacy of novel synthetic DNA vaccines for emerging infectious diseases

We are engineering enhanced consensus sequence DNA vaccines for use against a range of emerging infectious pathogens, including Dengue virus (DV), Chikungunya virus (CHIKV), Respiratory syncytial virus (RSV) and Middle Eastern Respiratory Syndrome virus (MERS). Our DNA constructs incorporate numerous improvements indicative of second-generation DNA vaccine technology, such as DNA optimization, RNA optimization, and electroporation (EP). We aim to ultimately measure the in vivo efficacy of these DNA plasmids in driving protective immune responses from various emerging infectious viruses. This will also include characterizing B and T cells immune responses involved in virus neutralization and clearance.

2) Generation of synthetic anti-sera for passive immunity against emerging infectious diseases

We are pioneering the use of antibody-encoding DNA plasmids as a novel prophylactic or therapeutic treatment. We characterize and purify neutralizing antibodies from infected sera, and then use novel technology to identify, isolate, and ultimately clone relevant mAbs into DNA vectors to generate full human IgG expression vectors. We are currently evaluating antibody-encoding DNA plasmids as prophylactic or therapeutic treatments for DV, CHIKV, RSV, MERS and other pathogens of interest. These antibody-encoding DNA plasmids have the potential to generate therapeutic levels of mAb in vivo through more cost-effective and simplified treatment regimens. Moreover, such plasmids provide a safe, non-live, and non-viral approach to deliver antibody-mediated immunity against pathogens within 1-2 days of delivery.

Selected Publications

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: 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, August 2015.

J Yan, C Tingey, R Lyde, T C Gorham, D K Choo, A Muthumani, D Myles, L P Weiner, K A Kraynyak, E L Reuschel, T H Finkel, J J Kim, N Y Sardesai, K E Ugen, K Muthumani and D B Weiner: Novel and enhanced anti-melanoma DNA vaccine targeting the tyrosinase protein inhibits myeloid-derived suppressor cells and tumor growth in a syngeneic prophylactic and therapeutic murine model. Cancer Gene Therapy 21(12)(507-517), December 2014.

Muthumani K, Wise MC, Broderick KE, Hutnick N, Goodman J, Flingai S, Yan J, Bian CB, Mendoza J, Tingey C, Wilson C, Wojtak K, Sardesai NY, Weiner DB.: HIV-1 Env DNA vaccine plus protein boost delivered by EP expands B- and T-cell responses and neutralizing phenotype in vivo. PLoS One 8(12): e84234, December 2013.

Muthumani K, Flingai S, Wise M, Tingey C, Ugen KE, Weiner DB: Optimized and enhanced DNA plasmid vector based in vivo construction of a neutralizing anti-HIV-1 envelope glycoprotein Fab. Hum Vaccin Immunother 9(10): 2253-2262, Oct 2013.

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.: 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, August 2011.

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: 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, January 2011.

Muthumani K, Choo AY, Zong WX, Madesh M, Hwang DS, Premkumar A, Thieu KP, Emmanuel J, Kumar S, Thompson CB, Weiner DB.: 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, February 2006.

Muthumani K, Hwang DS, Desai BM, Zhang D, Dayes N, Green DR, Weiner DB.: HIV-1 Vpr induces apoptosis through caspase 9 in T cells and peripheral blood mononuclear cells. J Biol Chem. 277(40): 37820-37831, October 2002.

Muthumani K,Choo AY, Shedlock DJ, Laddy DJ, Sundaram SG, Hirao L, Wu L, Thieu KP,Chung CW, Lankaram KM, Tebas P, Silvestri G, and Weiner DB: Human immunodeficiency virus type 1 Nef induces programmed death 1 expression through a p38 mitogen-activated protein kinase-dependent mechanism. J. Virol. 82(23): 11536-44, December 2008.

Muthumani K, Choo AY, Hwang DS, Premkumar A, Dayes NS, Harris C, Green DR, Wadsworth SA, Siekierka JJ, Weiner DB.: HIV-1 Nef-induced FasL induction and bystander killing requires p38 MAPK activation. Blood 106(6): 2059-68, September 2005.

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Last updated: 10/06/2015
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