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Faculty Members and Current Research

    capelluto
Daniel Capelluto Biochemistry and structural biology of protein-protein and protein-lipid interactions; protein domains engaged in Wnt signaling, protein domains that control blood clotting, multimodular proteins that control inflammation processes, lipid-binding proteins that mediate entry of oomycetes in plant cells
    Chen
Jing Chen Our current interests include coordinated motility in bacterial colony and mitotic signaling, with special emphasis on understanding the coupling between biological signaling and spatiotemporal regulation/mechanical interactions. Biological systems self-assemble into highly heterogeneous and dynamic structures. Spatiotemporal regulation and mechanical interactions constitute integrated components of biological signaling mechanisms, but in most cases their specific functional roles are not well understood yet. Modern experimental tools allow high resolution live-cell imaging and dynamic force measurement; however, it remains difficult or impossible to simultaneously track all biomolecules and their activities in the complex biological systems. To fill the unavoidable void, we weave experimental data into physically viable models, which provides insights into functional roles of spatiotemporal regulation and mechanical interactions. We typically work in close collaboration with experimental groups to ensure effective feedback between theory and experiments.
    cimini
Daniela Cimini Our lab is primarily interested in the cellular mechanisms responsible for inducing aneuploidy in somatic cells. Aneuploidy, the condition of a cell possessing an incorrect chromosome number, is well known for inducing severe pathological genetic syndromes (e.g., Down syndrome), and is a hallmark of cancer. Somatic cell aneuploidy arises as a consequence of inaccurate chromosome segregation during mitosis. Whereas many possible mitotic errors can cause inaccurate chromosome segregation, we believe that not all of them are equally likely to occur in the leaving organism, and that some of them represent a more severe threat than others to chromosome stability. By using a combination of live-cell imaging, quantitative light microscopy, protein inhibition and mathematical modeling we aim at identifying and characterizing the cellular mechanisms responsible for chromosome-segregation in both normal and cancer cells.
    finkielstein
Carla Finkielstein Cell, molecular, and structural biology, regulation of cell division process, molecular basis for breast cancer incidence; circadian control of cell proliferation, tumor resistance to radiation therapies, regulation of gene expression by circadian proteins, control of metastatic processes.
    fox
Michael Fox Synapses are sites that allow information to be passed between neurons and are essential for brain function. Their importance is highlighted by the fact that even minor synaptic abnormalities, caused by disease or neurotrauma, result in devastating neurological conditions. Understanding how CNS synapses are targeted, assembled, and maintained (or eliminated) is therefore essential to our understanding of neurological disorders. Our lab is specifically interested in understanding the cellular and molecular mechanisms that drive the initial targeting of synaptic partners to each other and the subsequent differentiation of these partners into functional synapses.
    friedlander
Michael Friedlander My research program is directed at understanding the processes that regulate alterations in synaptic efficiency between neurons within the cerebral cortex -synaptic plasticity- and how these cellular processes are affected during brain development, after experience including learning and in response to brain injury.
    hauf
Silke Hauf Cell division is a highly orchestrated process. Both daughter cells need to obtain a precise copy of the genetic information and of all other cellular material that they need to survive. Thousands of proteins are involved in the process with hundreds being important regulators. We want to understand how such a complex event can be reliably executed, despite fluctuations in cellular composition ('noise') and variation in the cell environment. We want to know whether cellular design principles resemble or differ from the principles that are implemented in man-made systems to achieve reliability. Because cell division is so central to life, much of the regulation is preserved throughout evolution. We use the unicellular eukaryote Schizosaccharomyces pombe (fission yeast) as a model organism and combine genetic techniques, advanced fluorescence microscopy, proteomics and computational modeling to explore the mechanisms of reliable cell division.
    Deb Kelly
Deborah Kelly My research focuses on developing innovative methodologies to study complex biological machinery. In particular, I am interested in using a combination of structural and functional tools to understand how signaling pathways influence human development and disease. Cryo-Electron Microscopy (EM) is an ideal technique to visualize macromolecular assemblies, such as ribosomes, at sub-nanometer resolution. Still, a major obstacle in the field is that many active cellular complexes are too labile or in too low abundance for conventional purification schemes. To address this issue, we developed the monolayer purification method and the functionalized Affinity Grid, that make it possible to rapidly purify complexes from crude cell lysates directly onto an EM Grid. These novel techniques provide a powerful approach for gathering structural information and allow us to view biological processes in a completely new fashion. We are now applying this technology to examine signaling complexes that regulate stem cell development in both normal and cancerous tissues. The knowledge gained from this line of research will shed light on the early events of stem cell commitment and cancer formation.
    kojima
Shihoko Kojima Circadian rhythmicity is a fundamental aspect of temporal organization in essentially every cell in the body, and modulates much of physiology, biochemistry, and behavior. In order to maintain daily cycles, cell-autonomous circadian oscillators drive rhythmic expression of approximately 5-10% of mRNAs to ultimately drive a wide range of rhythmic biological processes. We are interested in understanding 1) how the circadian clock regulates the rhythms of thousands of mRNAs and proteins to regulate rhythmic physiology and behavior. We use the mouse as an animal model system and integrate diverse approaches - genetics, genomics, bioinformatics, neuroscience, and molecular/cellular biology - to answer these questions.
    lazar
Iuliana Lazar Cancer is a disease of the cell cycle that results in uncontrolled proliferation of cells. In our laboratory, we explore the molecular mechanisms of breast cancer cell cycle regulation by using holistic, mass spectrometry-based systems biology approaches. We develop proteomic technologies for investigating the pathways that enable cancer cells to bypass tightly regulated molecular checkpoints, proliferate in an unrestrained manner, metastasize and hijack normal biological function. Further, we capitalize on the power of our proteomic data to identify novel therapeutic drug-targets, and to develop microfluidic architectures for targeted detection of biomarkers indicative of disease.
    Li
Liwu Li Molecular pathways controlling innate immunity and inflammation; dynamic programming of innate immune leukocytes; pathogenesis of actue chronic inflammatory diseases such as sepsis and atherosclerosis
    mukherjee
Konark Mukherjee The role of MAGUK (Membrane Associated Guanylate Kinase) proteins in neurodevelopment. Neurodevelopment proceeds through a series of events culminating into formation of productive neuronal network. One of the key final steps in neurodevelopment is refinement of transient connections i.e. strengthening and weakening/elimination of transient synapses, which depends on their individual activity. These highly plastic changes in transient synapses require activity-dependent signaling. Proteins involved in synaptic plasticity are obvious effector molecules involved in synaptic pruning or refinement. MAGUKs are a class of multi-domain scaffolding proteins present in both pre- and post-synaptic compartment. They play a crucial role in various forms of synaptic plasticity. Mutations in MAGUKs like CASK and SAP102 are often linked with neurodevelopmental disorders like X-linked mental retardation. The goal of our laboratory is to investigate the role of MAGUKs like CASK in neurodevelopment. Our lab uses both mouse and fly models of CASK knockout for this purpose. Besides animal work, the major thrust of the lab is to develop biological assays (biochemical, imaging, and electrophysiological techniques) to identify the molecular function and signaling pathways of CASK and other MAGUKs.
    schubot
Florian Schubot Structural and biophysical basis for virulence mechanisms in bacterial pathogens; regulation of the type III secretion system and biofilm formation in Pseudomonas aeruginosa; structural studies of chlamydial Inc proteins and their role in host invasion
    smyth
James Smyth The heart sets the pace.  If it's too quick or two slow, it's catastrophic for the rest of the body. Our lab is researching heart failure and the development of effective anti-arrhythmic treatments.
    tholl
Dorothea Tholl The Tholl Lab employs biochemical, molecular, and genomic tools to study the biosynthesis of plant chemical defenses, especially volatile compounds, and explores their physiology and ecological significance in above- and below-ground plant tissues. Current research includes: 1) Biochemistry and molecular biology of volatile compounds as messengers in above-ground plant-organism interactions; 2) Metabolic organization and function of chemical defenses in plant roots.
    tokuhisa

 

Jim Tokuhisa My lab focuses on two chemical defense systems that protect plants from attack by generalist herbivores. Crucifer plants produce glucosinolates, nontoxic glycosides, that are bioactivated when herbivores attack the plant. We humans recognize these bioactivated compounds as the sharp flavor components of arugula, horseradish, mustard, and wasabi. The bioactivating agent is an enzyme that is heavily modified after it has been synthesized in the plant. We are investigating how these unusual post-translational modifications contribute to plant fitness in plant-herbivore interactions. Plants of the Solanum genus produce steroidal glycoalkaloids as defense compounds against generalist herbivores. These compounds are the bitter flavors we associate with unripe tomatoes and the jackets of red potato tubers. The production of these compounds requires increased metabolic flux through the terpenoid biosynthetic pathway. The enzyme squalene synthase is a critical enzyme of this pathway and in potato is encoded by an unusually large gene family. We are looking at the individual members of the gene family to identify biochemcial and molecular features that contribute to the biosynthesis of the steroidal defense compounds.
    tyson
John Tyson Cell cycle regulation in budding yeast; estrogen responsiveness in breast cancer cells; innate immune responses; stochastic modeling of protein regulatory networks; cell division control in alpha-proteobacteria
    valdez
Greg Valdez We are interested in identifying molecules that protect synapses from the ravages of aging and age-related neurological diseases. Synapses are the sites where information is received and transmitted throughout the central nervous system and between motor neurons and muscles. They are also a primary site of entry for growth factors and other molecules that neurons and muscles need to properly function and survive. In much of our work, we study the motor neuron and muscle synapse, the neuromuscular junction. This is a large and readily accessible synapse that is significantly affected by normal aging and the progression of diseases, including amyotrophic lateral sclerosis. In parallel, we probe structural and molecular changes in the spinal cord and select brain synapses.
    walker
Richard Walker Cell and molecular biology - cytoskeleton, mitosis; cell motility; microtubule-related motor proteins; the visible cell
    winkel
Brenda Winkel Characterization of the architecture and localization of the Arabidopsis flavonoid enzyme complex using a variety of molecular, biochemical, and cell biological techniques