We study fundamental cell biology questions in the context of human health and disease. To better understand the molecular mechanisms of life processes and how they are corrupted by disease, our work focuses on the conserved pathways that control cellular communication and decision-making processes. The malfunction of these activities underlies a plethora of errors in key physiological events, and strongly contributes to the development of a growing list of metabolic diseases, neurodegenerative disorders, diverse cancers, and age-related illnesses. Although no universal mechanism may exist, our goal is to characterize key inter- and intra-cellular processes to provide a better understanding of precise signatures essential for biological timing and communication.
To achieve this, we aim to develop a cellular and biochemical framework that enables molecular characterization of biomolecular machines and complement this with high-resolution imaging techniques and protein engineering tools to investigate the key interactions facilitating the large remodeling of the cellular landscape. Such analyses are bound to be transformative for our understanding of the essential cellular functions and the roles of specific cells, subcellular regions, proteins, and lipids. These efforts will also help identify the molecular bases of human pathologies associated with the functional decline of cellular activity.
The long-term goal of our laboratory is to develop innovative approaches to decipher the links between cellular dysfunction and human disease and increase the probability of success in developing new therapeutic approaches.
Why do mitochondria matter?
Disease development is associated with a general functional decline in physiological activity, including mitochondrial processes. There is a growing understanding of how metabolic alterations, oxidative stress, DNA damage, inflammation, calcium dyshomeostasis, and several other factors may underlie the decline in cellular dynamics and function. For instance, the progressive deterioration of brain cell structure and function is often accompanied by mitochondrial dysfunction, impacting key cellular processes ranging from metabolism and signaling to differentiation and programmed cell death. Yet, we do not understand the mechanistic links between mitochondrial dysfunction, neurodegeneration, and nervous system pathologies. Investigating the timing, compartmentalization, communication, and localization of mitochondrial processes is critical for advancing our understanding of neuronal physiology, degeneration and regeneration, and may also offer potential intervention strategies.
How do cells communicate to improve health and viability?
The transfer of information between cells has been shown to facilitate metabolic coupling, resolve inflammatory pain, contribute to neuro-recovery mechanisms after stroke, and enhance tumorigenesis. How do cells decide which molecules should be released into the extracellular space? What are their functional roles upon internalization by recipient cells? Although no universal mechanism may exist, our goal is to characterize key intra- and extra-cellular processes to provide a better understanding of precise signatures essential for intercellular communication.
To achieve this, we aim to develop a biochemical framework that enables molecular characterization of cellular machines and complement this with high-resolution imaging techniques to investigate the key interactions facilitating the large remodeling of the cellular landscape. These efforts will help identify the molecular bases of human pathologies associated with cell-cell communication and increase the probability of success in developing new therapeutic approaches.
How do lipids regulate cellular function?
Our lab tackles a central challenge in cell biology: understanding how lipids cooperate with proteins to self-assemble into membranes of mutable shapes that define the organizational principles of cellular systems. Cells orchestrate spatial and temporal organization of critical biochemical processes to enable multiple, often competing, reactions to occur simultaneously. This cellular complexity is driven by lipid and protein catalysts, which play key roles in the modulation of cellular architecture, metabolism, and signaling. Thus, our research is focused on understanding the native principles of membrane dynamics in eukaryotic and bacterial systems. We combine molecular imaging and mechanistic investigations and develop novel approaches, including new visualization tools for monitoring lipid-lipid and lipid-protein interactions and unique in vitro reconstitutions to engineer complex biochemical processes in human and bacterial cells. This combination of experimental methods allows us to overcome the genetic, biochemical, and computational challenges to study dynamic processes in molecular detail and provide a critical foundation for understanding the mechanisms connecting lipids and cellular dynamics and function.