Rex L. Chisholm
Title: Professor and Director of the Center for Genetic Medicine
Research area: Molecular Genetics of Cell Motility and Molecular Motors
Degree: Ph.D.
Voice: 312.503.4151
Fax: 312.503.5994
e-mail: r-chisholm@northwestern.edu
Link to lab webpage : dicty.cmb.northwestern.edu/chisholm

Detailed research description: Movement is a fundamental characteristic of living things. The ability of cells to move is critical for normal embryogenesis and the formation of tissues, wound healing, and defense against infection; it also plays an important role in disease processes such as tumor metastasis. In addition, movement of cellular components within cells is necessary for chromosome separation during mitosis, hormone secretion, phagocytosis, and endocytosis. Molecular motors that move along actin-based microfilaments (myosin) and tubulin-based microtubules (dynein) power these cellular and intracellular movements. At the tissue and organism level the contraction of muscle, maintenance of blood pressure, and beating of the heart are also powered by these motor molecules. Mutations in one of these motor molecules, cardiac myosin, are responsible for an inherited heart disease called hypertrophic cardiomyopathy--a common cause of sudden death among otherwise healthy adults.

My laboratory's goal is to understand how these motors are regulated and work to convert chemical energy into mechanical force; to define the extent of their involvement in intracellular, cellular, and tissue function and their contribution to disease; and to ultimately begin to develop therapies for the treatment of disease caused by defects in these molecular motors. Our work uses two different experimental systems: the single celled eukaryotic organism Dictyostelium discoideum and mice and rats. We use molecular genetic techniques such as targeted gene disruption and in vitro mutagenesis in transgenic animals to manipulate myosin and dynein in vivo; cell biological techniques such as confocal microscopy to investigate the cellular consequences of the myosin and dynein mutations; biochemical techniques to purify and determine enzymatic properties of mutant myosin and dynein; biophysical techniques such as laser optical traps to monitor motor function by in vitro motility assays; and computer modeling to predict the structural consequences of mutations we introduce into these molecules.

Representative publications: 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. Pengxin Chen, Bruce D. Ostrow, Sherrie R. Tafuri and Rex   L. Chisholm. 1994. Targeted disruption of the   Dictyostelium RMLC gene produces cells defective in   cytokinesis and development. J. Cell Biol. 127, 1933-   1944. Bruce D. Ostrow, Pengxin Chen, and Rex L. Chisholm.   1994. Expression of a myosin regulatory light chain   phosphorylation site mutant complements the cytokinesis   and developmental defects of Dictyostelium RMLC null   cells. J. Cell Biol. 127, 1945-1955. 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. 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. Bernard M. Chaudoir, Patricia A. Kowalczyk and Rex L.   Chisholm. 1999. Myosin regulatory light chain mutation   affect enzyme function and kinetics. J. Cell Sci. 112,   1611-1620. Wendy A. Wolf, Teng-Leong Chew and Rex L. Chisholm.   1999. Regulation of cytokinesis. Cell. Mol. Life Sci. 55,   108-120.

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