Profile
Over the past two decades Dr Sharma's laboratory has integrated multi-disciplinary approaches within biochemistry, bioinformatics, cell biology and structural biology to understand eukaryotic parasite proteins. His laboratory has so far determined the crystal structures of nine aminoacyl-tRNA synthetase (ARS) enzymes from parasites and host. His lab pioneered the structural biology of ARS enzymes-inhibitor complexes and was the first to unravel enzyme-drug complexes of lysyl-, prolyl- and phenylalanyl-tRNA synthetases. Over the past decade, his research program on malaria parasite tRNA synthetases has led to >50 publications and three fully validated and druggable enzyme targets. Since then, numerous groups have mushroomed worldwide with a focus on drug target validation of tRNA synthetases, and with many of these he works collaboratively. In addition, his lab is increasingly focussed on malaria epidemiology with emphases on genomics.
Current Focus Areas
Dr. Sharma's lab focuses on structure-based inhibitor development on aminoacyl-tRNA synthetase (ARS) enzymes of parasites, vectors and host. His group has expanded their interests in epidemiology of vector borne diseases, genomics, digitalisation, malnutrition and climate change.
Selected Publications
Yadav CP, Hussain SSA, Mullick R, Rahi M, Sharma A. Climate zones are a key component of the heterogeneous presentation of malaria and should be added as a malariometric for the planning of malaria elimination. PLOS Glob Public Health. 2023 Jun 28;3(6):e0001878. doi: 10.1371/journal.pgph.0001878. eCollection 2023. PMID: 37379340
Yadav CP, Sharma A. National Institute of Malaria Research-Malaria Dashboard (NIMR-MDB): A digital platform for analysis and visualization of epidemiological data. Lancet Reg Health Southeast Asia. 2022 Jul 9;5:100030. doi: 10.1016/j.lansea.2022.100030. eCollection 2022 Oct. PMID: 37383658
Manickam Y, Malhotra N, Mishra S, Babbar P, Dusane A, Laleu B, Bellini V, Hakimi MA, Bougdour A, Sharma A. Double drugging of prolyl-tRNA synthetase provides a new paradigm for anti-infective drug development. PLoS Pathog. 2022 Mar 25;18(3):e1010363. doi: 10.1371/journal.ppat.1010363. eCollection 2022 Mar. PMID: 35333915
Sharma M, Malhotra N, Yogavel M, Harlos K, Melillo B, Comer E, Gonse A, Parvez S, Mitasev B, Fang FG, Schreiber SL, Sharma A. Structural basis of malaria parasite phenylalanine tRNA-synthetase inhibition by bicyclic azetidines. Nat Commun. 2021 Jan 12;12(1):343. doi: 10.1038/s41467-020-20478-5. PMID: 33436639
Jain V, Yogavel M, Kikuchi H, Oshima Y, Hariguchi N, Matsumoto M, Goel P, Touquet B, Jumani RS, Tacchini-Cottier F, Harlos K, Huston CD, Hakimi MA, Sharma A. Targeting Prolyl-tRNA Synthetase to Accelerate Drug Discovery against Malaria, Leishmaniasis, Toxoplasmosis, Cryptosporidiosis, and Coccidiosis. Structure. 2017 Oct 3;25(10):1495-1505.e6. doi: 10.1016/j.str.2017.07.015. Epub 2017 Aug 31. PMID: 28867614