Mitotic Spindle Assembly

During mitosis, a set of intricate mechanisms and checkpoints ensure proper mitotic microtubule spindle formation and equal chromosome segregation. Through large-scale proteomic and functional screens, we have identified many novel proteins that associate with and are required for mitotic microtubule spindle assembly.  Among these proteins are Kinesin motor proteins, phosphatases, carboxyl methyltransferases, carboxypeptidases, and ubiquitin ligases (see below).  We are interested in identifying their interacting proteins and/or substrates, and determining their mechanistic function. These novel proteins influence the outcome of cell division and in a broader context have implications in cancer. 

Microtubule-associated Disease-linked Ubiquitin Ligases

Human diseases including cancer, neurodegeneration, and muscle wasting involve the ubiquitin-proteasome system (UPS), the major cytosolic pathway for proteolysis.  Ubiquitin ligases, components of the UPS, regulate protein stability by recognizing specific substrates and targeting them for destruction.  Recently the lab has identified several disease-linked ubiquitin ligases that when depleted display defective microtubule dynamics.  To understand the connection between ligase deficiency and its resultant disease, we have begun to identify the components, substrates and regulators of these ligases through complex purifications. 

RNAi and Small Molecule Screens

The lab has an active interest in identifying gene depletions and small molecules capable of inhibiting cell division and activating the cells intrinsic programmed cell death pathway (Apoptosis).