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The Shanthini Sockanathan Laboratory uses the developing spinal cord as our major paradigm to define the mechanisms that maintain an undifferentiated progenitor state and the molecular pathways that trigger their differentiation into neurons and glia. The major focus of the lab is the study of a new family of six-transmembrane proteins (6-TM GDEs) that play key roles in regulating neuronal and glial differentiation in the spinal cord. We recently discovered that the 6-TM GDEs release GPI-anchored proteins from the cell surface through cleavage of the GPI-anchor. This discovery identifies 6-TM GDEs as the first vertebrate membrane bound GPI-cleaving enzymes that work at the cell surface to regulate GPI-anchored protein function. Current work in the lab involves defining how the 6-TM GDEs regulate cellular signaling events that control neuronal and glial differentiation and function, with a major focus on how GDE dysfunction relates to the onset and progression of disease. To solve the...se questions, we use an integrated approach that includes in vivo models, imaging, molecular biology, biochemistry, developmental biology, genetics and behavior. view less
The Gould Laboratory studies vesicles, known as exosomes and microvesicles (EMVs), that can be taken up by neighboring cells, completing a pathway of intercellular vesicle traffic.
Our laboratory studies the molecular mechanisms of EMV biogenesis and uptake, and their contributions to cell polarity, cell-to-cell interactions, and intercellular signaling. We also examine the ways in which HIV and other retroviruses use the exosome biogenesis pathway for the formation of infectious virions, and the consequences of their EMV origin.
Research in the Claypool Lab is focused on defining how lipids and membrane proteins interact to establish and maintain normal mitochondrial function and how derangements in this complex relationship result in pathophysiology. We have demonstrated that yeast lacking tafazzin recapitulates all of the phospholipid abnormalities observed in human patients and many of the mitochondrial defects.
Another major project in our lab focuses on the mitochondrial ADP/ATP carrier that is required for oxidative phosphorylation. Researchers are studying how these novel interactions help establish normal mitochondrial function, the biochemical details of these associations, and whether disturbances in these assemblies can contribute to mitochondrial dysfunction.
The Structural Enzymology and Thermodynamics Group uses a combination of molecular biology, biochemistry and structural biology to understand the catalytic mechanisms of several enzyme families. Additionally, researchers in the group are studying protein-ligand interactions using structural dynamics. They are able to apply their knowledge of the mechanisms of these enzymes and of binding energetics to develop targets for drug design.
The Michaelis Laboratory's research goal is to dissect fundamental cellular processes relevant to human health and disease, using yeast and mammalian cell biology, biochemistry and high-throughput genomic approaches. Our team studies the cell biology of lamin A and its role in the premature aging disease Hutchinson-Gilford progeria syndrome (HGPS). Other research focuses on the core cellular machinery involved in recognition of misfolded proteins. Understanding cellular protein quality control machinery will ultimately help researchers devise treatments for protein misfolding diseases in which degradation is too efficient or not enough.
The research in the Svetlana Lutsenko Laboratory is focused on the molecular mechanisms that regulate copper concentration in normal and diseased human cells. Copper is essential for human cell homeostasis. It is required for embryonic development and neuronal function, and the disruption of copper transport in human cells results in severe multisystem disorders, such as Menkes disease and Wilson's disease. To understand the molecular mechanisms of copper homeostasis in normal and diseased human cells, we utilize a multidisciplinary approach involving biochemical and biophysical studies of molecules involved in copper transport, cell biological studies of copper signaling, and analysis of copper-induced pathologies using Wilson's disease gene knock-out mice.
The Agnew Laboratory examines the structure, mechanism and regulation of ion channels that mediate the action potential in nerve and muscle, as well as intracellular calcium concentrations. Much of our work has centered on voltage-activated sodium channels responsible for the inward currents of the action potential. These studies encompass biochemical, molecular biological and biophysical studies of Na channel structure, gating and conductance mechanisms, the stages of channel biosynthesis and assembly, and mechanisms linked to channel neuromodulation.
In recent molecular cloning and expression studies, we have characterized mutations in the human muscle sodium channel that appear to underlie certain inherited myopathies. New studies being pursued in our group also address the questions of structure, receptor properties, and biophysical behavior of intracellular calcium release channels activated by inositol-1,4,5-triphosphate. These channels are expressed at extremely high levels ...in selected cells of the central nervous system, and may play a role in modulating neuronal excitability. view more
The objective of the Xiao Group's research is to study the dynamics of cellular processes as they occur in real time at the single-molecule and single-cell level. The depth and breadth of our research requires an interdisciplinary approach, combining biological, biochemical and biophysical methods to address compelling biological problems quantitatively. We currently are focused on dynamics of the E. coli cell division complex assembly and the molecular mechanism in gene regulation.
Ion channels are pore-forming membrane proteins gating the flow of ions across the cell membrane. Among their many functions, ion channels regulate cell volume, control epithelial fluid secretion, and generate the electrical impulses in our brain. The Qiu Lab employs a multi-disciplinary approach including high-throughput functional genomics, electrophysiology, biochemistry, and mouse genetics to discover novel ion channels and to elucidate their role in health and disease.
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