Research in the Alex Kolodkin Laboratory is focused on understanding how neuronal connectivity ...is established during development. Our work investigates the function of extrinsic guidance cues and their receptors on axonal guidance, dendritic morphology and synapse formation and function. We have investigated how neural circuits are formed and maintained through the action of guidance cues that include semaphorin proteins, their classical plexin and neuropilin receptors, and also novel receptors. We employ a cross-phylogenetic approach, using both invertebrate and vertebrate model systems, to understand how guidance cues regulate neuronal pathfinding, morphology and synaptogenesis. We also seek to understand how these signals are transduced to cytosolic effectors. Though broad in scope, our interrogation of the roles played by semaphorin guidance cues provides insight into the regulation of neural circuit assembly and function. Our current work includes a relatively new interest in understanding the origins of laminar organization in the central nervous system. view more

Research in the Biophotonics Imaging Technologies (BIT) Laboratory focuses on developing optica...l imaging and nano-biophotonics technology to reduce the random sampling errors in clinical diagnosis, improve early disease detection and guidance of biopsy and interventions, and improve targeted therapy and monitoring treatment outcomes. The imaging technologies feature nondestructiveness, unique functional and molecular specificity, and multi-scale resolution (from organ, to architectural morphology, cellular, subcellular and molecular level). The nano-biophotonics technologies emphasize heavily on biocompatibility, multi-function integration and fast track clinical translation. These imaging and nano-biophotonics technologies can also be potentially powerful tools for basic research such as for drug screening, nondestructive assessment of engineered biomaterials in vitro and in vivo, and for studying brain functions on awake animals under normal or controlled social conditions. view more

Complexity in signaling networks is often derived from co-opting one set of molecules for multi...ple operations. Understanding how cells achieve such sophisticated processing using a finite set of molecules within a confined space--what we call the "signaling paradox"--is critical to biology and engineering as well as the emerging field of synthetic biology.

In the Inoue Lab, we have recently developed a series of chemical-molecular tools that allow for inducible, quick-onset and specific perturbation of various signaling molecules. Using this novel technique in conjunction with fluorescence imaging, microfabricated devices, quantitative analysis and computational modeling, we are dissecting intricate signaling networks.

In particular, we investigate positive-feedback mechanisms underlying the initiation of neutrophil chemotaxis (known as symmetry breaking), as well as spatio-temporally compartmentalized signaling of Ras and membrane lipids such as phosphoinositides. In parallel, we also try to understand how cell morphology affects biochemical pathways inside cells. Ultimately, we will generate completely orthogonal machinery in cells to achieve existing, as well as novel, cellular functions. Our synthetic, multidisciplinary approach will elucidate the signaling paradox created by nature. view more