Ph.D. in Cell Biology, Institute of Cell Biology, NAS of Ukraine, 2005
Postdoctoral Scholar, University of California, San Diego, 2006-2010
Cell and Molecular Biology and Physiology (CMBP)
My lab is studying lipophagy, the selective autophagy of lipid droplets (LDs), which regulates lipid metabolism in most eukaryotic cells. Lipophagy is accomplished by delivery of the intracellular LDs from the cytosol to the lysosomes (animals) or vacuoles (yeast). As in other autophagic pathways, the core autophagic machinery is essential for lipophagy. However, how it recognizes the LDs when lipophagy is induced is unknown. Also, it is not clear how lipophagy is kept in check the rest of the time. Therefore, lipophagy selectivity and regulation are the key gaps in this field and a research focus of our lab. The mechanistic understanding in these areas is critical for the precise control of lipophagy in humans for the prevention and treatment of a whole plethora of lipid accumulation diseases, including atherosclerosis, fatty liver, metabolic syndrome of aging and obesity.
Recently, we discovered a novel Negative regulator of lipophagy 1 (Nrl1) that specifically represses lipophagy but not non-selective autophagy in yeast. Our data suggest that the function of Nrl1 is conserved across the species and that it promotes the accumulation of LDs in zebrafish and murine macrophages. Since a specific suppressor of lipophagy would be such a good therapeutic target for upregulation of the pathway in so many disease states, the first project of our research program is dedicated to the regulation of lipophagy by Nrl1. We study the molecular mechanism of lipophagy repression by Nrl1, how specific it is for the lipophagy pathway and the impact of Nrl1 on lipid metabolism at both the cellular (yeast and macrophages) and organismal (zebrafish and mouse) levels.
The second project of our research program is focused on the selectivity mechanisms of lipophagy. By tracking down the regulatory effects of Nrl1, we will identify its effectors, the lipophagy-specific selectivity factors. We will also extend the selectivity studies to the LD proteome and identify selectivity factors that might be regulated in an Nrl1-independent fashion. Comprehensive analyses of the lipophagy-specific factors is an important challenge to be addressed, since such factors define the lipophagy pathway, can be used to control it and are expected to be the new autophagic proteins. The evolutionary conserved lipophagy factors will be studied further at both the cellular (yeast and macrophages) and organismal (zebrafish and mouse) levels.
Lab Members Position Devesh Pant Post Doctoral Associate firstname.lastname@example.org Muhammad Rahman Post Doctoral Associate email@example.com Ankit Shroff Post Doctoral Associate firstname.lastname@example.org Nimna Wijewantha PhD Student email@example.com Akshara Erasani Undergraduate Student firstname.lastname@example.org Chetna Batra UAP Student email@example.com Victoria Carlino UAP Student firstname.lastname@example.org Makayla Nudo UAP Student email@example.com
Lab Phone Number: 404-413-5348