Research
Currently, my primary focus revolves around studying LACTB, a mitochondrial tumor suppressor protein. This protein is unique in its ability to form filaments and contains a serine protease active site. However, the connection between these characteristics and its role in suppressing tumors remains unclear. My research suggests that LACTB plays a crucial role in maintaining mitochondrial dynamics and function, as well as regulating lipid metabolism. To unravel the molecular mechanisms underlying LACTB's tumor-suppressive effects, I plan to employ a combination of reconstitution, cell culture, and mouse model approaches. By gaining a comprehensive understanding of LACTB's actions, my work aims to contribute to the development of biomarkers and innovative therapeutic strategies for cancer treatment.
Mitochondria
Lipid droplets
Membrane nanotubes
Supported Lipid Bilayer
Before my current focus, I worked as a postdoc with Prof. Roop Mallik's lab at the Tata Institute of Fundamental Research in 2019. The lab's emphasis was on understanding the molecular details of lipid droplet-endoplasmic reticulum (LD-ER) contact sites. Drawing on my prior expertise, I devised a novel assay to reconstitute LD-ER contact sites using rat liver-derived components. My findings revealed the metabolic sensitivity of LD-ER contact formation, with increased interactions observed in LDs and ER from fed rats compared to fasted ones. Additionally, I identified Rab18 and phosphatidic acid as key factors in these contact site formations.
During my doctoral studies under the guidance of Prof. Thomas Pucadyil, my research aimed to refine assays for studying membrane fission. While existing methods such as liposomes and giant unilamellar vesicles could simulate fission reactions, they lacked specificity, hindering our understanding of the molecular mechanisms underlying protein-driven scission in vesicular transport. I developed an innovative assay system involving supported membrane tubes, enabling real-time visualization of dynamin-catalyzed scission. This paved the way for investigating a less-explored dynamin family member, Drp1, which is involved in mitochondrial and peroxisomal processes. My efforts culminated in successfully reconstituting Drp1-mediated membrane fission.
In the future, my focus will be directed towards unraveling the intricate mechanisms through which cells regulate their lipid composition. This endeavor will be bolstered by the unique amalgamation of skills in cell and reconstitution biology that I have cultivated throughout my training. These skills will undoubtedly play a pivotal role in dissecting the multifaceted nature of this complex challenge.
