Research in the Adam D. Sylvester Lab primarily focuses on the way in which humans and primates move through the environment, with the aim of reconstructing the locomotor repertoire of extinct hominins and other primates. We use a quantitative approach that involves the statistical analysis of three-dimensional biological shapes, specifically musculoskeletal structures, and then link the anatomy to function and function to locomotor behavior.
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 optical 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.
Complexity in signaling networks is often derived from co-opting one set of molecules for multiple 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
The Sesaki Lab is interested in the molecular mechanisms and physiological roles of mitochondrial fusion.
Mitochondria are highly dynamic and control their morphology by a balance of fusion and fission. The regulation of membrane fusion and fission generates a striking diversity of mitochondrial shapes, ranging from numerous small spheres in hepatocytes to long branched tubules in myotubes. In addition to shape and number, mitochondrial fusion is critical for normal organelle function.
Epilepsy affects 1-3% of the population and can have a profound impact on general health, employment and quality of life. Medial temporal lobe epilepsy (MTLE) develops in some patients following head injury or repeated febrile seizures. Those affected may first suffer spontaneous seizures many years after the initial insult, indicating that the neural circuit undergoes a slow pathologic remodeling over the interim. There are currently no methods of preventing the development of MTLE. It is our goal to better understand the process in order to slow, halt, and ultimately reverse it.
Our laboratory draws on electrophysiology, molecular biology, and morphology to study the contribution of dysregulated neurogenesis and newborn neuron connectivity to the development of MTLE. We build on basic research in stem cell biology, hippocampal development, and synaptic plasticity. We work closely with colleagues in the Institute for Cell Engineering, Neurology, Neurosurgery, Biomedical Engineering..., and Radiology. As physician neuropathologists our grounding is in tissue alterations underlying human neurologic disease; using human iPSC-derived neurons and surgical specimens we focus on the pathophysiological processes as they occur in patients.
By understanding changes in cell populations and morphologies that affect the circuit, and identifying pathologic alterations in gene expression that lead to the cell-level abnormalities, we hope to find treatment targets that can prevent the remodeling and break the feedback loop of abnormal activity > circuit change > abnormal activity.view more
In the Zhou Lab, the overall goal of our research is to understand the molecular mechanisms underlying development of the mammalian nervous system. Specifically, we are interested in understanding how neurons generate their complex morphology and form proper circuitries during development and how neurons regenerate to restore connections after brain or spinal cord injuries.