At the Devreotes lab, we study how cells polarize and migrate, either spontaneously or under external cues. We identify different genetic and biochemical components of signal transduction and cytoskeletal networks and dissect how they coordinate to define the "logic" of the circuitry, which in turn, regulate chemotaxis, random migration, macropinocytosis, and other associated cellular processes. In the past, our studies elucidated the intercellular communication process that Dictyostelium uses to self-organize in response to external cues. We identified family of first chemoattractant receptors that were demonstrated to mediate chemotaxis and cell-cell signaling. We discovered that phosphoinositides play a key role in chemotaxis and in defining the basic strategy that eukaryotic cells use to sense gradients and spatiotemporally organize signaling and cytoskeletal events. We were first to demonstrate that shallow spatial gradients in G-protein activation leads to dramatic amplification of PI3K activity at the leading edge of the migrating cells. We introduced multiple new conceptual advances to cell migration and polarity field, including LEGI or Local Excitation Global Inhibition model of directional sensing and adaptation, biased coupled excitable network model of autonomous signal transduction and chemotaxis, and biophysical models of plasma membrane self-organization that dynamically regulate polarity in migrating cells.
We use Dictyostelium discoideum amoeba, mammalian leukocytes (macrophages and neutrophils), and different cancer cell lines as our model systems. We extensively use cutting-edge cellular engineering approaches, synthetic biological and optogenetic tools, and high-end microscopy techniques, in conjunction with stochastic computational models. In the process, we also developed multiple new tools to perturb specific genetic/biochemical pathways (and even nonspecific biophysical properties), in a spatiotemporally controlled fashion. We are eager to learn all the fundamental aspects of cell migration and polarity. A comprehensive understanding of these fascinating cellular processes would be the key to develop therapies to diverse pathologies such as autoimmune diseases, cardiovascular diseases, cognitive deficits, and cancer metastasis. A few recent areas of interest are shown below.
To learn more about a few of our recent areas of interest, please follow the link below: