The role of lipids in different cellular processes
Lipids are a broad class of metabolites with important biological functions. The cellular lipidome (i.e., the totality of lipids in cells) is very diverse. Mammalian cells express tens of thousands of different lipids. This chemical diversity arises from unique backbones that make up major lipid families. In addition to this, different building blocks that can be chemically linked to these backbones contribute to lipid diversity. Traditionally, lipids are recognized as the fundamental components of cellular membranes, separating cells from their surroundings as well as creating micro-compartments within cells. Therefore, the composition of lipids can affect the physical properties of the membranes and, as a consequence, cell function. Recently, new roles of lipids have been discovered, including transmitting key signals within and between cells. Mechanisms of cellular signaling constitute a fundamental area of study in cell biology as it underlies vital processes such as cellular division, death, and migration.
Our approach is to:
(1) study important processes and determine the changes in lipid composition
(2) determine how these lipids are regulated at the biochemical level.
We then carefully perturb these biochemical pathways and investigate to what extent these perturbations affect the biological processes we study. Identification of these pathways allows us to discover novel biochemical mechanisms of lipid regulation and identify new lipid-related pathways that are involved in critical biological processes. Our approach integrates state of the art analytical methods (i.e., methods to identify, quantify and study lipid levels in cellular extracts) and other (bio)chemical ones.
The goal of our research program is to delineate how subtle differences in lipid structure affects their roles in biology in different types of programmed cell death (i.e., apoptosis and necroptosis) and cellular senescence. Cell death and cellular senescence (permanent cessation of cell division) are two natural processes that terminate the proliferative life of cells. These processes play central roles in aging, cancer formation and progression, and response to chemotherapy. We are studying lipid regulation in these processes and identifying new lipid species that play a role in cell death and senescence. For example, we identified very long chain fatty acids that are involved in necroptosis. Our results suggest that these very long chain fatty acids are linked to the inflammation that occurs during necroptosis and necroptosis-linked diseases.
In addition to these primary research directions, we collaborate with other groups to answer questions on the function of lipids and other small molecules based on their precise chemical structure. Recently, we have been interested in how per-and-polyfluoroalkyl substances (PFAS) interact with biological systems.