…We are a Team of Lipid Enthusiasts…
The role of lipids in different cellular processes
The focus of our research group is to elucidate the role of a subset of small molecule metabolites, lipids (also known as fats), in different cellular fates. Our approach is to: (1) study important processes and determine the changes in lipid composition and (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. My broad training in chemistry and cell biology puts me in a unique position to integrate and exploit these approaches.
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 surrounding 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.
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 another project, we identified a lipid family that is mostly known for storing excess fats in our cells (i.e., triacylglycerols) to play an essential role in apoptosis and senescence. We have shown that the formation of triacylglycerols that have many double bonds can limit the toxic effects of cell death and senescence. Within this framework, we have also identified a lipid-related protein called CD36, thought to help cells import and use lipids, as central to senescence.
The knowledge we have gained from our research has helped to identify new lipid players and lipid-related pathways in cell death and cellular senescence and enables a better understanding of these processes at the fundamental level.
In addition to these primary research directions, we have collaborated with other groups to answer questions on lipids’ function based on their precise chemical structure. High-resolution mass spectrometry-based detection methods now enable us elucidate the role of biomolecules in different cellular processes. One of the focuses of my laboratory is to develop methods and apply global metabolomics and proteomics approaches to different questions that are related to environmental and human health. For example, using specifically designed methods, we recently elucidated the biochemical regulation of value-added biochemicals in non-model green algae and the effect of sub-lethal exposure of silver nanoparticles on plant growth.