Research & Publications
Extensive Research Description
Dr. Kumar's training in virology and immunology and her dissertation identified the non-structural protein 3 of the Japanese encephalitis virus (JEV) as an important vaccine candidate through the protective immune response this protein elicited in asymptomatically-infected individuals, which also reduced neurological symptoms in symptomatically-ill cohorts in the JEV-endemic regions in South India. Her thesis work was published as 6 first-authored papers in international, well-recognized peer-reviewed journals. For her post-doctoral studies, she pioneered the use of siRNAs for treating flaviviral infections and developed a platform for the transvascular delivery of siRNA into the CNS using a peptide from the Rabies virus (PLOS Medicine, 2006; Nature, 2007). Continuance of this research interested at Yale has continued to be the advancement of novel therapeutic strategies for acute infections caused by Zika and West Nile virus. Work from the laboratory has demonstrated that intranasal administration of siRNAs with RVG at late stages of West Nile virus encephalitis can prevent a fatal outcome while promoting long-term immunity (Cell Host and Microbe, 2018).
Kumar P, Sulochana P, Nirmala G, Chandrashekar R, Haridattatreya M, Satchidanandam V. Impaired T helper 1 function of nonstructural protein 3-specific T cells in Japanese patients with encephalitis with neurological sequelae. J Infect Dis. 2004 189(5):880-91.
Kumar P, Lee SK, Shankar P and Manjunath N. A single siRNA suppresses fatal encephalitis induced by two different flaviviruses. PLOS Medicine 2006 3(4):e96.
Kumar P, Wu H, McBride JL, Jung KE, Moon Hee Kim, Davidson BL, Lee SK, Shankar P and Manjunath N. Transvascular delivery of small interfering RNA to the central nervous system. Nature 2007. 448(7149):39-43.
Beloor J, Maes N, Ullah I, Uchil P, Jackson A, Fikrig E, Lee, SK and Kumar P*. Small interfering RNA-mediated control of virus replication in the CNS is therapeutic and enables natural immunity to West Nile virus. Cell Host and Microbe 2018. 23(4):549-556. PMC6074029.
See Also: Comment Barouch-Bentov R, Einav S. Turning Up Your Nose for a Flaviviral Encephalitis Cure. Cell Host Microbe. 2018; 23(4):427-429. PMID: 29649437; PMC7104965.
A major strength of the Kumar laboratory is expertise in humanized mouse models for HIV infection. This has resulted in many successful collaborations and co-authored manuscriptsas well as consultations for opinion and work shops at the NIH in advancing humanized mouse models for the study of HIV-1. In collaboration with the Mothes laboratory at Yale, the Kumar lab identified a critical role for macrophages expressing CD169 in the in vivo capture of retroviruses at lymphoid organs for transinfecting virus-susceptible target cells. The mechanism appears to be a common route for transmission of both murine (MLV) and human (HIV) retroviruses in animal models of infection (Science, 2015). Along the lines of treatment with the Anderson and Saltzman laboratories at Yale, the Kumar lab has been investigating the potency of novel picomolar NNRTIs as a treatment for HIV-AIDS as long-acting formulations (Mol. Pharmacology, 2017; PNAS USA, 2018, ).
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, and 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. PMCID: PMC4761823.
Sewald X, Ladinsky MS, Uchil1 PD, Beloor J, Pi R, Herrmann1C, Motamedi N, Murooka TT, Brehm MA, Greiner DL, Shultz LD, Mempel TR, Bjorkman PJ, Kumar P*, and Mothes W. Retroviruses use CD169-mediated trans-infection of permissive lymphocytes to establish infection. Science. 2015, Oct 30;350(6260):563-7. PMC4651917
Kudalkar SN, Beloor J, Quijano E, Spasov KA, Lee WG, Cisneros JA, Saltzman WM, Kumar P*, Jorgensen WL, Anderson KS. From in silico hit to long-acting late-stage preclinical candidate to combat HIV-1 infection. Proc Natl Acad Sci U S A. 2018 ;115(4):E802-E811. PMC5789948
Ventura JD, Beloor J, Allen E, Zhang T, Haugh KA, Uchil PD, Ochsenbauer C, Kieffer C, Kumar P*, Hope TJ, Mothes W. Longitudinal bioluminescent imaging of HIV-1 infection during antiretroviral therapy and treatment interruption in humanized mice. PLoS Pathog. 2019; 15(12):e1008161. PMCID: PMC6917343.
An important focus of my research is in vivo gene-therapy. My laboratory develops gene delivery platforms to enable gene and oligonucleotide delivery in a highly targeted manner to specific cell types in vivo. This is of immense significance as it obviates the need for ex-vivo manipulation of cells and transplantation protocols. The advantage of these systems is that they enable delivery to cells like neurons, human T cells and hematopoietic stem cells that are extremely resilient to nucleic acid uptake. We have contributed to the field of gene delivery by studying mechanisms for direct delivery of nucleic acids into the cytoplasm (eg: Chemistry and Biology, 2015); developing delivery systems for efficient nucleic acid delivery to hard-to-transfect cells like embryonic stem cells, neurons and T cells (eg: Small, 2015; Cell, 2008) and adapting these delivery systems for the treatment of viral and metabolic diseases in preclinical animal models (Nature 2007; Molecular Therapy Nucleic Acids, 2016).
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. Chemistry & Biology. 2015; 22(1):50-62. PMC4320807
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. 2015; 11(17):2069-79.
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. Molecular Therapy Nucleic acids. 2016; 5:e280. PMC5012549
Ullah I, Chung K, Beloor J, Kim J, Cho M, Kim N, Lee KY, Kumar P*, Lee SK. Trileucine residues in a ligand-CPP-based siRNA delivery platform improve endosomal escape of siRNA. J Drug Target. 2017; 25(4):320-329. PMID: 27820977.
T-Lymphocytes; RNA Interference; Infectious Disease Medicine; Molecular Targeted Therapy