Professor of Cellular & Molecular Medicine
Ph.D., U.C. San Francisco
The Oegema lab takes parallel approaches in mammalian cells and using the C. elegans embryo as a metazoan model system to study cell division and development. The three main project areas in thelab are described below.
1. Functional Genomics of embryogenesis: Genome sequencing projects have generated a comprehensive "parts" list of the genes required to build an organism, providing an inventory of cellular building blocks. However, the function of many genes remains undiscovered, preventing us from obtaining a clear view of cellular and developmental pathways and how they are affected in human disease. Recent systematic efforts, using cells from humans and model organisms, such at the nematode C. elegans, have aimed to systematically catalog gene function. Generating functional maps with the power to resolve differences in gene function requires a lot of information, which is typically obtained by high-content screening. In a high-content screen, genes are individually inhibited, and the consquences are documented using microscopy-based assays. Our lab is developing high-content screening methods that allow us to generate a numerical "fingerprints" for each gene to place it within an embryogenesis gene network and predict its function. Our goal is to generate an integrated functional network for the set of 2500 C. elegans genes required for embryogenesis. As ~75% of these genes are conserved in humans and about 1/3 are currently uncharacterized, this approach will predict the function of a large number of human genes.
2. Cytokinesis: Cytokinesis completes cell division by physically remodeling the mother cell to form the two daughter cells. In animal cells, cytokinesis is accomplished by constriction of a cortical contractile ring that assembles around the cell equator between the segregated chromatin masses. The contractile ring forms in response to signals from the anaphase spindle and constricts until only a narrow bridge connects the two daughter cells. We are pursuing projects aimed a understanding: (1) the signaling between the spindle and cortex that directs cytokinesis, (2) the mechanics of the contractile ring and its relationship to the surrounding cortex during constriction, and (3) abscission, the process that completes cytokinesis to diffusionally isolate the cytoplasm in the nascent daughter cells and alter membrane topology to form two distinct cells.
3. Centriole Duplication: Centrioles are subcellular organelles composed of a 9-fold symmetric microtubule array that perform two important functions: (1) they build centrosomes that organize the microtubule cytoskeleton, and (2) they template cilia, microtubule-based projections with sensory and motile functions. Centrioles duplicate once per cell cycle in a poorly understood process that is tightly coupled to the cell cycle to ensure the presence of precisely two centrosomes in mitotic cells. Abnormalities in centrosome number and structure are common features of cancer cells, suggesting that decoupling of centrosome duplication from the cell cycle contributes to tumorigenesis. We have are taking parallel approaches in C. elegans and human cells to define the proteins required for centriole and centrosome assembly, to understand the roles of centrioles and centrosomes in cell physiology, and to determine how centrosome number becomes disregulated during tumorigenesis.