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Rex L. Chisholm, PhDProfessor
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Movement is a fundamental characteristic of life. Cell movement is critical for normal embryogenesis, tissue formation, wound healing and defense against infection. It is also an important factor in diseases such as cancer metastasis and birth defects. Movement of components within cells is necessary for mitosis, hormone secretion, phagocytosis and endocytosis. Molecular motors that move along microfilaments (myosin) and microtubules (dynein) power these movements. Our goal is to understand how these motors produce movement and are regulated. We wish to define their involvement in intracellular, cellular, and tissue function and disease—with the long-term goal of developing therapies for the treatment of diseases caused by defects in these molecular motors.
Our work involves the manipulation of myosin and dynein function in the single celled eukaryote Dictyostelium, cultured mammalian cells and transgenic and knockout mice. Yeast two hybrid screens to identify proteins that interact with or regulate myosin and dynein and characterization of gene expression are being used to define the pathways regulating myosin and dynein. To analyze the biological significance of myosin and dynein, we use confocal and digital microscopy of living cells, analysis of cell movement, vesicle transport and cell division. We employ biochemical techniques including heterologous expression, enzyme purification and characterization, and analysis of how phosphorylation state affects physiological function. We are pursuing signal transduction studies to understand the physiologically important pathways that regulate cell motility and biophysical studies such as in vitro motility assays to understand how these molecular motors function at the molecular level.
Shuo Ma, Leda Trivinos-Lagos, Ralph Graf and Rex L. Chisholm. 1999. Dynein intermediate chain mediated dynein-dynactin interaction is required for interphase microtubule organization and centrosome replication and separation in Dictyostelium. J. Cell Biol. 147, 1261-1274.
Tung-Ling L. Chen, Wendy A. Wolf and Rex L. Chisholm. 1998. Cell type specific rescue of myosin function during Dictyostelium development defines two distinct cell movements required for culmination. Development 125, 3895-3903.
Richard S. Pollenz, Tung-Ling L. Chen, Leda Trivinos-Lagos and Rex L. Chisholm. 1992. The Dictyostelium essential light chain is required for myosin function. Cell 69, 951-962.
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View Publications by Rex Chisholm listed in the National Library of Medicine (PubMed). |
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