Brian Mitchell, PhD
Associate Professor, Cell and Molecular Biology; Feinberg School of Medicine
Research Program
Link
Cancer-Focused Research
Centriole Duplication. Centrioles are microtubule based structures with nine fold symmetry that are involved in both centrosome organization and aster formation during cell division. During the normal cell cycle centrioles duplicate once, generating a mother / daughter pair, and in most post-mitotic vertebrate cells the mother centriole then goes on to form the basal body of a sensory cilium. Abnormalities in the duplication of centrioles (and centrosomes) are prevalent in many cancers suggesting a link between centriole duplication and cancer progression. My laboratory is addressing this fundamental question in cell biology from a novel direction with the use of Xenopus motile ciliated cells. Ciliated cells are unique among vertebrate cells in that they naturally generate hundreds of centrioles therefore providing a great system for studying the regulation of centriole duplication. Understanding how nature has overcome the typically tight regulation of centriole duplication will lend insight into the molecular mechanisms of cancer progression. Cilia Polarity. The ability of ciliated epithelia to generate directed fluid flow is an important aspect of diverse developmental and physiological processes including proper respiratory function. To achieve directed flow, ciliated cells must generate 100-200 cilia that are polarized along a common axis both within and between cells. My lab is currently working towards understanding the molecular mechanisms for how cell polarity is coordinated as well as how individual cilia interpret the cells polarity. Epithelial Integrity. In order for cancer cells to metastasize they must migrate out of the primary tumor. This process requires that cells move in a directed manner and that they have the ability to bypass cellular junctions. Very little is known of this process due to the lack of experimentally pliable model systems. We are using the developing skin of Xenopus embryos to understand how cells break through epithelial barriers during development as a model for understanding the molecular mechanisms required for any cell to achieve this. We anticipate that understand the developmental regulation of this process will lend insight into the cellular mechanisms that get hijacked during cancer metastasis.