We use live cell imaging in cultured adult rat or mouse DRG neurons for many studies. We also examine mouse phenotypes and protein-protein interactions among motor regulators. Finally we  have a keen interest in understanding how kinase pathways impact dynein function.

Current Projects

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1. Using LIS1 missense mutations to study dynein regulation

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​LIS1 mutations in humans cause lissencephaly, a severe developmental brain abnormality. LIS1 binds directly to dynein's ATPase motor subunit. Evidence to date indicates that LIS1 and an interacting protein, NDEL1, are positive regulators of dynein. We use several assays to explore if and how LIS1 mutations impact dynein interactions and dynein-dependent transport.

2. Role of LIS1 in astrocytes

​LIS1 function in astrocytes has not been explored, but because it controls dynein in many cell types its role in these important brain cells needs to be investigated. We have detected substantial LIS1 in cultured rat astrocytes where it is enriched at centrosomes and interestingly, also accumulates around engulfed nuclei of dying neurons.

3. LIS1 depletion in adult mice

​We found that inducing LIS1 depletion in adult mice causes neurological phenotypes and rapid lethality. We hypothesize this is due to defective sensorimotor and cardiorespiratory circuits. To this further we will use targeted iKO to deplete LIS1 specifically in projection neurons.