How do cells “decide” to change their shape and/or move and what happens once such decision has taken?
Cells integrate the various signals that are transduced from their microenvironment and respond to it by remodeling their cytoskeleton, a highly dynamic complex network of protein filaments that reorganizes continuously to enable changes of cell shape and movement. From bacteria searching for nutrients to neurons searching for synaptic partners, at some point in their life cycle most cells must remodel their cytoskeleton in order to change their shape and/or move.
In recent years, several important players were discovered that affect cell shape and movement. Among them, manipulation of Pyk2, a protein tyrosin kinase, leads to drastic phenotype at the cellular and organism levels. So far we were able to show that Pyk2 localize with cortactin and Vinculin at the sites where cells invade extracellular matrix.
Our labs long-term goal is to understand how cells encounter these multiple signals in their complex extracellular environment and translate those signals into the component processes that dictate whether a cell changes its shape or moves toward or away from a signal. Dysregulation of this fundamental process is at the heart of numerous physiological disorders, including developmental,neurological, immune diseases, cardiovascular diseases, and cancer. As such, it is imperative to gather a better understanding of how cells move normally, why they move aberrantly in the context of various diseases, and importantly, how we can modulate these processes when treating disease. Research in the lab is focused on addressing these fundamental questions. Using a multidisciplinary approach, which combines advanced molecular and cellular biology methods, nano-scale micropatterned array analysis, RNAi-mediated genetic manipulations, phosphoproteomics analysis, transgenic and knockout mice models and cutting edge high-resolution in vitro and in vivo imaging, we try to understand and characterize, at the molecular, cellular, and whole organism levels, the cytoskeletal signaling networks that regulate cell migration and invasion.
A better understanding of the molecular mechanisms that regulate and execute these processes would suggest novel clinical targets for treating various human disorders and diseases and is the fundamental goal of our research.