Assistant Professor of Biology

Phone – 540-568-5184

Office Hours

Research

Retinal degenerative diseases are a large and diverse group of disorders that affect approximately 3.5 million people worldwide. These diseases are loosely defined as disorders which cause photoreceptor cell death and finally result in a loss of vision. In the eye, photoreceptor cells are responsible for detecting light and initiating the biochemical signal that is eventually transmitted to the brain. In photoreceptors light detection and signaling begins with the activation of the photopigment, rhodopsin. Genetically there are more than 140 genes that when mutated result in photoreceptor cell death. Most of these genes are not directly connected to rhodopsin-driven signaling, but when mutated they disrupt proper trafficking of rhodopsin. This disruption rhodopsin localization promotes photoreceptor cell death. Despite the variation in genetic origin of retinal degenerative diseases, my research focus is to identify common cellular pathways that drive retinal disease progression.

In all cells the process of autophagy is required for the degradation of intracellular components within lysosomal. The term autophagy literally means self (auto) eating (phagy), and is necessary for cell survival.  This process allows the cell to remove old, damaged, and toxic proteins and organelle. The resulting products of degradation can be recycled by cells for the synthesis of new intracellular components. In the retina, several studies have indicated that autophagy may play an important role in protecting the retina from light-induced degeneration and age-related macular degeneration. Defects in autophagy have been linked to several neurodegenerative diseases such as, Alzheimer’s, Huntington’s, amyotrophic lateral sclerosis (ALS), and Mucolipidosis type IV (MLIV). The molecular pathways that help protect against neuronal cell death are not clearly understood, and even less is known about photoreceptor cell death. I will use genetic research models to characterize the role of autophagy in protecting photoreceptors from degeneration and uncover the common molecular components that drive retinal degenerative disease.

    1.     Walker, M. T. and Montell, C. “Suppression of the motor deficit in a mucolipidosis type IV mouse model by bone marrow transplantation” 2016 Hum Mol Genet  25 (13): 2752-2761

    2.     Walker, M. T.; Rupp, A.; Elsaesser, R.; Güler, A. D.; Sheng, W.; Weng, S. ; Berson, D.; Hattar, S.; and Montell, C.  “RdgB2 is required for dim-light input into intrinsically photosensitive retinal ganglion cells.” 2015  Mol Biol Cell Oct. 15; 26 (20): 3671-8

    3.     Walker, M. T.; Brown, R. L.; Cronin, T. W.; Robinson, P. R. ”Photochemistry of retinal chromophore in mouse melanopsin.” 2008 Proc Natl Acad Sci USA 105: 8861-5.

    4.     Newman, L. A.; Walker, M. T.; Brown, R. L.; Cronin, T. W.; and Robinson, P. R. "Melanopsin forms a functional short-wavelength photopigment." 2003 Biochemistry 42 (44): 12734-8.

    5.     Stelzl, U.; Zengel, J. M.; Tovbina, M.; Walker, M.; Nierhaus, K. H.; Lindahl, L.; and Patel, D. J. "RNA-structural mimicry in Escherichia coli ribosomal protein L4-dependent regulation of the S10 operon." 2003 J Biol Chem 278 (30): 28237-45.

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