Research
We seek to understand essential cellular processes — using yeast as a model organism — in order to shed new light on neurodegeneration, cancer and other diseases.
We seek to understand essential cellular processes — using yeast as a model organism — in order to shed new light on neurodegeneration, cancer and other diseases.
Little is known about the underlying causes of neurodegeneration and other neurological diseases. Our lab recently made the unexpected discovery that altering the PI3,5P2 lipid signaling pathway to half its normal levels causes profound neurodegeneration and lethality in mice. Based on these observations we are focused on the following questions:
The above studies are being pursued in yeast, cultured mammalian cells and mice.
Directed organelle movement is critical during cell division and differentiation. During cell division, a new cell-center is chosen, organelle volume doubles, and each type of organelle is accurately distributed to their proper location in the new daughter cells. Likewise during cellular differentiation, organelles move to new intracellular locations. This movement is essential for cells to acquire new functions. Defects in organelle movement have wide-ranging effects. For example defects in myosin Va based motility cause neurological diseases and defects in pigmentation, whereas defects in myosin Vb are linked to an inherited form of infant mortality.
Our lab studies yeast Myo2, a direct homologue of myosin Va and Vb. Major discoveries include our discovery of one of the first organelle-specific receptors. Analysis of the receptor showed that it is a direct target of a major cyclin-dpendent kinase, Cdk1. This is a key part of the mechanism that coordinates organelle inheritance with other cell-cycle processes, such as DNA replication. In addition we found that the spatially regulated destruction of the organelle-specific complex, is required to retain the organelle at its correct destination. Moreover, we have found a well-conserved Rab GTPase binding site on the myosin V cargo-binding domain.
We are focused on the following questions:
These questions are being pursued in yeast, yet our overall goal is to determine the mechanisms of cargo attachment to myosin V in higher eukaryotes.