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Bih-Hwa Shieh, Ph.D.

Associate Professor, Department of Pharmacology

Research Description

My research program explores the mechanisms leading to retinal degeneration. Retinal degeneration is characterized by the progressive loss of photoreceptors in the eye leading a loss of vision and blindness. There are many conditions that lead to dysfunction or death of photoreceptors. My lab is particularly interested in mechanisms that affect the sensory transduction pathway involving in the light detection. In photoreceptors light activates rhodopsin that couples to the G-protein leading to the activation of phospholipase C.  Subsequently, the TRP channel is open resulting in the influx of Ca2+ that brings about depolarization of photoreceptors. This signaling process is highly regulated to achieve temporal resolution of the visual response. Unregulated visual signaling often leads to retinal degeneration. We believe that knowledge on the regulation of the visual signaling would shed lights into potential strategies to help prevent retinal degeneration.

We use Drosophila as our experimental model organism for insights into mechanisms of retinal degeneration. Inherited retinal degeneration in Drosophila has been explored for insights into similar processes in humans. In Drosophila, we employ a multi-disciplinary approach by combining molecular biological, cell biological, biochemical and genetics strategies to uncover the molecular basis underlying retinal degeneration.

Currently, we are investigating the contribution of arrestins (Arr1 and Arr2) and protein kinase C in retinal degeneration. Both arrestins belong to the evolutionarily conserved family that plays a critical role to modulate the function of rhodopsin. In particular, we are exploring how phosphorylation of rhodopsin that promotes its endocytosis may orchestrate retinal degeneration.

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Vanderbilt Faculty Profile 

Vanderbilt Brain Institute (VBI)