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Karuppiah Muthumani, MS., PhD

Karuppiah Muthumani, MS., PhD

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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
Education:
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

Project I: DNA vaccine development for emerging infectious diseases using consensus vaccine approach

Effective vaccines are still needed to combat a number of deadly diseases including Human immunodeficiency virus (HIV), Flu, Middle Eastern Respiratory Syndrome (MERS) and several emerging mosquito-borne pathogens such as Dengue Virus (DV), West Nile Virus (WNV) and Chikungunya Virus (CHIKV). Over the past 25 years, multiple vaccine platforms have been explored to induce protective viral-specific immunity. DNA is one such platform and has already been studied in numerous clinical protocols. The platform’s safety has been well-documented in the clinic with more than 20,000 persons having received DNA vaccines with no adverse effects. In addition to its enviable safety record, the technology is made attractive by the simplicity of its engineering and production as compared to live attenuated and killed viral vaccines. DNA vaccines are also very stable and, therefore, ideal candidates for third world distribution where an effective vaccine is most needed. We are engineering several vaccines into enhanced consensus DNA constructs using the improvements to second-generation DNA vaccines such as DNA optimization, RNA optimization, and electroporation (EP) have given the platform-increased immunogenicity and comparing their ability to drive immune responses for HIV, DV, RSV, CHIKV and MERS virus.


Project II: Generation of synthetic anti-sera for passive immunity against infectious diseases

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

Selected Publications

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(doi: 10.1038/cgt.2014.56), November 2014.

Shedlock DJ, Tingey C, Mahadevan L, Hutnick N, Reuschel, EL, Kudchodkar S, Flingai S, Yan Y, Kim JJ, Ugen KE, Weiner DB Muthumani K: Co-Administration of Molecular Adjuvants Expressing NF-Kappa B Subunit p65/RelA or Type-1 Transactivator T-bet Enhance Antigen Specific DNA Vaccine-Induced Immunity. Vaccines 2: 196-215, March 2014.

Fagone P, Muthumani K, Mangano K, Magro G, Meroni PL, Kim JJ, Sardesai NY, Weiner DB, Nicoletti F.: VGX-1027 modulates genes involved in the LPS-induced TLR-4 activation and in a murine model of Systemic Lupus Erythematosus. Immunology Feb 2014 Notes: DOI: 10.1111/imm.12267.

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.

Flingai S, Czerwonko M, Goodman J, Kudchodkar SB, Muthumani K, Weiner DB: Synthetic DNA Vaccines: Improved Vaccine Potency by Electroporation and Co-Delivered Genetic Adjuvants. Front Immunology 4: 354, November 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), September 2013.

Ouma GO, Rodriguez E, Muthumani K, Weiner DB, Wilensky RL, Mohler ER 3rd. : In vivo electroporation of constitutively expressed HIF-1α plasmid DNA improves neovascularization in a mouse model of limb ischemia. J Vasc Surg 13(00865-3), July 2013.

Chaaithanya IK, Muruganandam N, Anwesh M, Rajesh R, Ghosal SR, Kartick C, Prasad KN, Muthumani K, Vijayachari P: HLA class II allele polymorphism in an outbreak of Chikungunya fever in Middle Andaman, India. Immunology May 2013 Notes: 10.1111/imm.12128.

Bao H, Ramanathan AA, Kawalakar O, Sundaram SG, Tingey C, Bian CB, Muruganandam N, Vijayachari P, Sardesai NY, Weiner DB, Ugen KE, Muthumani K.: Nonstructural Protein 2 (nsP2) of Chikungunya Virus (CHIKV) Enhances Protective Immunity Mediated by a CHIKV Envelope Protein Expressing DNA Vaccine. Viral Immunology 26(1): 75-83, Feb 2013.

Shedlock DJ, Talbott KT, Wu SJ, Wilson CM, Muthumani K, Boyer JD, Sardesai NY, Awasthi S, Weiner DB.: Vaccination with synthetic constructs expressing cytomegalovirus immunogens is highly T cell immunogenic in mice. Hum Vaccin Immunother 1(8(11)), Nov 2012.

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Last updated: 05/29/2015
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