T-Lymphocytes; RNA Interference; Infectious Disease Medicine; Molecular Targeted Therapy
Molecular Virology: Virology laboratories
The Kumar laboratory conducts translational research with a main focus on the development of novel gene therapies for viral infections. Over the last 7 years as faculty at Yale, Dr. Kumar’s laboratory has been involved in understanding pathogenesis of RNA viruses like HIV and West Nile virus in relevant small animal models and expanding research efforts for prevention and treatment of infections caused by these viruses. Notable advances from the group have been the development and testing of novel gene therapeutic strategies for HIV in humanized mice, with the goal of enabling in vivo gene therapy in humans.
Extensive Research Description
The current focus of my lab is to refine the above methods and use them to investigate key aspects of HIV immunopathogenesis and AIDS-associated T cell loss. In addition we have also developed a novel method for the specific delivery of nucleic acids into neuronal cells and used this to treat flaviviral infections like West Nile and Zika viruses in mouse models.
- Akkina R, Allam A, Balazs AB, Blankson JN, Burnett JC, Casares S, Garcia JV, Hasenkrug KJ, Kashanchi F, Kitchen SG, Klein F, Kumar P, Luster AD, Poluektova LY, Rao M, Sanders-Beer BE, Shultz LD, Zack JA. Improvements and Limitations of Humanized Mouse Models for HIV Research: NIH/NIAID "Meet the Experts" 2015 Workshop Summary. AIDS Res Hum Retroviruses. 2016 32(2):109-19.
- Kim J, Chung K, Choi C, Beloor J, Ullah I, Kim N, Lee KY, Lee SK, Kumar P**. Silencing CCR2 in Macrophages Alleviates Adipose Tissue Inflammation and the Associated Metabolic Syndrome in Dietary Obese Mice. Mol Ther Nucleic Acids. 2016 5:e280.
- Sewald X, Ladinsky MS, Uchil PD, Beloor J, Pi R, Herrmann C, Motamedi N, Murooka TT, Brehm MA, Greiner DL, Shultz LD, Mempel TR, Bjorkman PJ, Kumar P**, Mothes W. Retroviruses use CD169-mediated trans-infection of permissive lymphocytes to establish infection. Science. 2015 350(6260):563-7.
- Liu S, Jackson A, Beloor J, Kumar P**, Sutton RE. Adenovirus-Vectored Broadly Neutralizing Antibodies Directed Against gp120 Prevent Human Immunodeficiency Virus Type 1 Acquisition in Humanized Mice. Hum Gene Ther. 2015 26(9):622-34.
- Zeller S, Choi CS, Uchil PD, Ban HS, Siefert A, Fahmy TM, Mothes W, Lee SK, Kumar P**. Attachment of cell-binding ligands to arginine-rich cell-penetrating peptides enables cytosolic translocation of complexed siRNA. Chem Biol. 2015 22(1):50-62.
- Beloor J, Ramakrishna S, Nam K, Seon Choi C, Kim J, Kim SH, Cho HJ, Shin H, Kim H, Kim SW, Lee SK, Kumar P**. Effective gene delivery into human stem cells with a cell-targeting Peptide-modified bioreducible polymer. Small. 2015 11(17):2069-79.
- Schleifman EB, McNeer NA, Jackson A, Yamtich J, Brehm MA, Shultz LD, Greiner DL, Kumar P**, Saltzman WM, Glazer PM. Site-specific Genome Editing in PBMCs With PLGA Nanoparticle-delivered PNAs Confers HIV-1 Resistance in Humanized Mice. Mol Ther Nucleic Acids. 2013 2:e135.
- Kumar P*, Ban HS, Kim SS, Wu H, Pearson T, Greiner D, Laouar A, Yao J, Haridas V, Habiro K, Yang YG, Jeong JH, Lee KY, Kim YK, Kim SW, Peipp M, Fey GH, Manjunath N, Shultz LN, Lee SK and Shankar P. (2008). T cell-specific siRNA delivery suppresses HIV-1 infection in humanized mice. Cell. 134(4):577-86.
- Kumar P*, Wu H, McBride JL, Jung KE, Moon Hee Kim, Davidson BL, Lee SK, Shankar P and Manjunath N. (2007). Transvascular delivery of small interfering RNA to the central nervous system. Nature. 448(7149):39-43.
- Kumar P*, Lee SK, Shankar P and Manjunath N. A single siRNA suppresses fatal encephalitis induced by two different flaviviruses. PLOS Medicine 2006 Feb 14;3(4):e96. PMCID: PMC1361782