Cells must rapidly adapt to fluctuating environmental conditions to maintain energy and lipid homeostasis. Altered lipid storage in cells underlies numerous debilitating metabolic diseases (e.g. obesity, diabetes, atherosclerosis) and has been implicated in cancer, aging and viral lifecycle. To understand the aberrant physiology underlying metabolic diseases it is important to determine the mechanisms that cells use to monitor and functionally adapt to their changing environments.

Nearly every cell type stores energy as triacylglycerol in lipid droplets, an endoplasmic reticulum-derived organelle that is conserved from yeast to humans and is composed of a neutral lipid core encircled by a phospholipid monolayer. Proteins decorating the surface of lipid droplets regulate fat storage and mobilization. For example, specialized proteins called lipases localize to lipid droplets and can degrade triacylglycerol. Controlling the activity of these lipases represents an attractive approach for drug development. Despite the inherent relevance to human diseases, lipid droplets are arguably the least studied and most poorly understood organelle. This disparity stems from an enduring dogma that lipid droplets are inert storage compartments. We now know that lipid droplets are actually extremely dynamic, reacting to environmental stimuli and actively controlling fat storage and cellular energy homeostasis. This recognition has led to a revolution in lipid droplet research, and the scientific community is now confronted with many critical questions: How do lipid droplets form? How are the proteins on the surface of lipid droplets controlled? How does the cell detect nutrient status and communicate this to lipid droplets in order to maintain the balance between storage and utilization of fat? Perhaps most importantly, how can we manipulate lipid droplet function to treat disease?

Research in our laboratory seeks to elucidate the mechanisms that regulate lipid droplet biogenesis and functions in response to fluctuating conditions. We are also interested in defining the mechanisms by which cells combat and prevent lipotoxic damage and cell death. To address these complex questions, our laboratory integrates a unique combination of systems biology (proteomic and functional genomic), chemical biology, and mechanistic cell biology strategies. The long-term goal of our research is to discover fundamental cellular mechanisms controlling lipid homeostasis that can be manipulated as novel therapeutic strategies for the treatment of diseases, including metabolic diseases and cancer.

For more information, visit our website – olzmannlab.com.