- M.G. McCool Professor of Ophthalmology, Department of Ophthalmology
- Adjunct Associate Professor, Department of Cell Biology
- Mentoring Faculty, Oklahoma Center for Neuroscience
- Neuroprotective survival pathways regulated by receptor and non-receptor tyrosine kinases and receptor and non-receptor tyrosine phosphatases.
- Cross communication between rhodopsin and tyrosine kinase/phosphatase signaling in photoreceptors.
- Phosphoinositide signaling in the neuroprotection of the retina.
- Adapter proteins in recruiting the signaling complexes to mediate photoreceptor neuroprotection.
- PhD, Biochemistry, Andhra University, India
Postdoctoral Training, Molecular Biology, University of Saskatchewan, Saskatoon, Canada
Insulin receptors (IR) and insulin signaling proteins are widely distributed throughout the central nervous (CNS) system. Disregulation of IR signaling in the CNS has been linked to the pathogenesis of neurodegenerative disorders such as Alzheimer’s and Parkinson’s disease. IR maintains retinal neuronal cells and insulin receptor defects contribute to photoreceptor cell death. We discovered that IR signaling in rods is controlled by growth factor receptor bound protein 14 (Grb14), an upstream regulator of the IR, and requires photobleaching of rhodopsin for membrane targeting. Grb14 prevents IR dephoshorylation by protein tyrosine phosphatase 1B (PTP1B), a tyrosine phosphatase specific to the IR. Our recent studies clearly established a down regulation of IR signaling due to increased retinal PTP1B activity in animal models of retinitis pigmentosa, diabetic retinopathy and Leber Congenital Amaurosis, LCA-type.
Studies are underway in our laboratory to target PTP1B in these disease models. Our new and innovative approaches to target PTP1B will facilitate future translational application of our work, with the goal of applying our findings to the clinical care of human retinal degenerative disease including diabetic retinopathy. We are also investigating the role of phosphoinositide 3-kinase (PI3K) signaling pathway in retinal neuroprotection. We recently found age-related cone degeneration occurred in the cone-specific PI3K knockout mice but rod viability was not affected. These studies suggest that rods communicate survival signals to cones through the cone PI3K pathway. Studies are underway in our laboratory to test this hypothesis.
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