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Elaine Bearer
Professor, Pathology and Laboratory Medicine
M.D., Ph.D., University of California, S. F., 1983
[email protected]
Box G-B5, Brown University
Providence, RI 02912-G
401 863.3478
http://research.brown.edu/myresearch/Elaine_Bearer
Research Summary
A basic concept in pathology is that abnormalities in cellular structure lead to physiological malfunction and the signs and symptoms of disease. Many of the diseases associated with cytoskeletal malfunction occur with aging, including thrombosis leading to stroke and cardiovascular disease, cancer cell invasion, and Alzheimer's senile dementia. In our laboratory, we study the molecular mechanisms that create cell shape and how cells respond to the environment by changing shape. Actin filaments are the main source of cell shape, and we have focused our work on these. Using a proteomics approach, we identified all of the actin- binding proteins present in human cells, and developed a strategy to identify which are essential for key cellular activities. We have only studied a few of these so far, and many more remain in our freezer for future students and post-doctoral fellows to investigate.
By developing a novel high-throughput assay applicable to small molecule discovery, we were able to definitively link individual proteins to specific cellular processes. We are also mining the microarray databank for cytoskeletal protein expression patterns in cancer, comparing metastatic and primary tumors. We are now applying our knowledge of the cell's molecular architecture to develop an understanding of specific human diseases. Recent published work that exemplify this approach towards such an understanding of pathologic process includes:
- Identification of the Arp2/3 complex as the key regulator of platelet shape change, the first step in thrombosis (clotting).
- Identification of a human gene, kptin, as responsible for an inherited deafness and platelet disorder, DFNA 4.
- Reconstitutions of Herpes Simplex Virus transport in the giant axon and identification of motor recruitment devices and cytoskeletal tracks, with correlations to neurodegenerative diseases such as Alzheimer's Dementia.
- Determination of actin-based transport in axons and identification of the molecular motors involved.
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