Research Area
Cell Biology
Research Interests
IIn real estate, the golden rule is “location, location, location". Indeed, the same analogy also applies to our cells, where the proper location of cellular macromolecules, such as proteins, is crucial for the functioning of the smallest unit of life. The primary focus of my research group is to understand mechanisms of protein trafficking to lysosomes, which are compartments that degrade the cellular macromolecules and recycle their constituents. Indeed, lysosomes play a vital role in our survival, as reflected by more than 70 lysosomal storage diseases caused by defects in the functioning of this organelle. Recent findings suggest that lysosome dysfunction is associated with more common human diseases, such as cancer, neurodegenerative disorders, and obesity. Our previous studies have identified the molecular players that mediate fusion of lysosomes with vesicles to deliver the cargo. This molecular machinery involves small GTP binding proteins and their effectors, such as the multisubunit protein complex known as the "HOPS complex". Human patients lacking a functional HOPS complex have a significantly shorter lifespan and exhibit respiratory problems and mental retardation. My research group is also studying how intracellular bacterial pathogens use the host cell transport system to proliferate and survive. For instance, our previous study has shown that Salmonella Typhimurium, the causative agent of Salmonellosis, which is a frequent cause of food-related illness, uses the host cell's lysosomal proteins to promote its intracellular growth and survival. This study has important implications for Salmonellosis treatment as it identifies novel targets for drug development.
2020 - 2023 : Editor, Journal of Cell Science
2019 - 2021 : Board of Reviewing Editors, eLife
2019 - 2022 : Early Career Advisory Board, Journal of Cell Biology
2018 - 2020 : Editorial Board Member, Traffic
Since Jan 2020 : India Alliance DBT/Wellcome Trust Senior Fellow, Department of Biological Sciences, IISER-M (India)
Since Apr 2018 : Associate Professor, Department of Biological Sciences, IISER-M (India)
2012 - 2018 : India Alliance DBT/Wellcome Trust Intermediate Fellow, Department of Biological Sciences, IISER-M (India)
2011 - 2018 : Assistant Professor, Department of Biological Sciences, IISER-M (India)
2009 - 2011 : Postdoctoral Research Fellow, Department of Rheumatology, Immunology and Allergy, Brigham and Women’s Hospital/Harvard Medical School, Boston (USA)
2005 - 2009 : Ph.D., Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, Nebraska (USA)
2000 - 2004 : B.Tech., Biotechnology, School of Biotechnology, Guru Gobind Singh Indraprastha University, New Delhi (India)
National:
2023 Awarded INSA Associate Fellowship
2022 One of the finalists of NASI-Scopus Young Scientist Award
2020 Awarded BM Birla Science Prize in Biology
2019 Awarded Wellcome Trust/DBT-India Alliance Senior Fellowship
2019 Awarded INSA-Professor Har Swarup Memorial Award
2018 Awarded DBT-National Women Bio-scientist Award
2018 Awarded NASI-Young Scientist Platinum Jubilee Award
2018 Awarded INSA Medal for Young Scientist
2018 Selected to Indian National Young Academy of Science (INYAS, INSA)
2017 Awarded SERB-Women Excellence Award
2015 Awarded IISER-Mohali Best Teacher Award
2015 Received Young Associateship of the Indian Academy of Sciences (IASc)
2012 Awarded Wellcome Trust/DBT-India Alliance Intermediate Fellowship
International:
2021 Selected for TWAS Young Affiliateship from the Central and South Asian Region
2019 Profile featured: “People & Ideas” column by Journal of Cell Biology
2019 Profile featured: “Future of Biochemistry: The International Issue” by Biochemistry
2017 Profile featured in “Cell Scientist to Watch” column by the Journal of Cell Science
Kshitiz Walia, Abhishek Sharma, Sankalita Paul, Priya Chouhan, Gaurav Kumar, Rajesh Ringe, Mahak Sharma and Amit Tuli. SARS-CoV-2 virulence factor ORF3a blocks lysosome function by modulating TBC1D5-dependent Rab7 GTPase cycle. Nature Communications 15(1), 2024. URL, DOI
Shalini Rawat, Dhruba Chatterjee, Rituraj Marwaha, Gitanjali Charak, Gaurav Kumar, Shrestha Shaw, Divya Khatter, Sheetal Sharma, Cecilia Heus, Nalan Liv, Judith Klumperman, Amit Tuli and Mahak Sharma. RUFY1 binds Arl8b and mediates endosome-to-TGN CI-M6PR retrieval for cargo sorting to lysosomes. Journal of Cell Biology 222(1), 2022. URL, DOI
A Tuli and M Sharma. How to do business with lysosomes: Salmonella leads the way. Current Opinion in Microbiology 47:1-7, 2019.
Rituraj Marwaha, Subhash B Arya, Divya Jagga, Harmeet Kaur, Amit Tuli and Mahak Sharma. The Rab7 effector PLEKHM1 binds Arl8b to promote cargo traffic to lysosomes. Journal of Cell Biology 216(4):1051–1070, March 2017. URL, DOI
Mahak Sharma. Salmonella exploits the host endolysosomal tethering factor HOPS complex to promote its intravacuolar replication. PLOS Pathogens, 2017.
Mahak Sharma. DQ-Red BSA Trafficking Assay in Cultured Cells to Assess Cargo Delivery to Lysosomes. 2017.
D Khatter, A Sindhwani and M Sharma. Arf-like GTPase Arl8: Moving from the periphery to the center of lysosomal biology. Cellular Logistics 5(3), 2015.
S Garg, M Sharma, C Ung, A Tuli, D Barral, D Hava, N Veerapen, G Besra, N Hacohen and M Brenner. Lysosomal Trafficking, Antigen Presentation, and Microbial Killing Are Controlled by the Arf-like GTPase Arl8b. Immunity 35(2):182-193, 2011.