Research Areas

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, regulates 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 the first family of 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 the 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 developing therapies for diverse pathologies such as autoimmune diseases, cardiovascular diseases, cognitive deficits, and cancer metastasis. Please visit our research page to learn more. The recent areas of interest are provided below.

Genetic and Systemic Dissection of Signaling Network

Which genetic components are involved in specific signal transduction cascades? How do cells coordinate numerous signaling and cytoskeletal events via internal feedback loops? How do cells decide when and where to activate a specific signaling event so that they can polarize and migrate correctly? How do cells resolve different conflicting environmental cues and determine how to spatiotemporally regulate stochastic activities? These are some questions we are focused on.

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Membrane Biophysics and Lipid Biology of Migrating Cell

How does the plasma membrane acts as the hub of signal transduction during cell migration and polarity? How do different classes of membrane proteins dynamically compartmentalize into specific membrane regions? How is the symmetry breaking process initiated in plasma membrane? How do different lipid compositions and biophysical properties of membrane domains define the signaling state? How does the plasma membrane integrate information to encode templates for self-organization? Our research aims to address these questions.

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Cell Biology of Oncogenesis and Cancer metastasis

Which alterations in polarity signaling pathways result in oncogenesis? How do defects in cell migration transform normal cells to cancer cells? How do cancer cells differ from normal cells in terms of the spatiotemporal organization of signaling and cytoskeletal events? Do these organizational changes reprogram the energetics and metabolism of cancer cells? We are really interested in finding answers to these questions.

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