James E. Bear
Cancer Cell Biology
Area of interest
My lab focuses on actin-based cell motility. Actin-based motility is a key component in many cellular processes relevant to clinical problems such as cancer metastasis, birth defects and compromised immune function. We are using both molecule-based and unbiased genetic/proteomic approaches to understand the fundamental problem of cell migration and other aspects of actin-based motility. We utilize the techniques of high-resolution live cell microscopy, biochemistry, gene silencing/disruption and other molecular manipulations to uncover some of the underlying mechanisms of cell motility.
Most of our effort is focused on the role that Coronins play in cell migration and other actin-based processes. Coronins are a highly conserved family of F-actin binding proteins containing both WD40 repeats and potential Arp2/3 binding sites. In Dictyostelium, these proteins are strongly localized to the leading edge of migrating cells. Together, these observations led us to hypothesize that Coronins coordinate signal transduction and actin dynamics at the leading edge of migrating cells. While some information is known about the yeast and Dictyostelium homologues of these proteins, they have been poorly studied in mammalian systems. To study these proteins, we use cell biological, biochemical and molecular approaches. We have begun generating and characterizing reagents to study the mammalian Coronins including GFP-tagged expression constructs and polyclonal antibodies to selected family members. Major structural features such as the WD40 repeats and putative Arp2/3 binding site will be mutated and the effect on localization/function analyzed. To identify interacting proteins, two-hybrid approaches and biochemical purification of Coronin-containing complexes are being developed. In addition, overexpression, RNAi-mediated knockdown and dominant-negative approaches will be utilized to determine Coronin's role in cell motility.
Awards and Honors
- 2001-2004, Leukemia and Lymphoma Society Special Fellow
- 2000, NIH NRSA Award
- 1999-2000, Anna Fuller Molecular Oncology Fellow
- 1997, ASCB Predoctoral Travel Award
- 1993-1995, NIH Biochemistry, Cellular and Molecular Biology Training Grant recipient
- 1993, Phi Beta Kappa, Davidson College chapter
- 1989-1993, Samuel H. Bell Memorial Scholar, Davidson College