Visvanathan Ramamurthy, PhD

Professor

Organization:

West Virginia University School of Medicine

Department:

Ophthalmology and Visual Sciences

Classification:

Faculty

Professor & Chairman

Organization:

West Virginia University School of Medicine

Department:

Biochemistry

Classification:

Faculty

• PhD, Wesleyan University, 1998

[2020]

The Ramamurthy lab aims to decipher the biochemical pathways that control the complex processing of information through neurons to the brain. We use the visual system as a model to comprehend this process. In vision, defects in light signal processing result in neuronal death and blindness. Several recent studies have established the link between mutations in various genes to blinding diseases. However, the functional role of these genes and why defects in these genes cause blindness remains elusive. In our research group, we use various molecular, biochemical and physiological approaches to probe the biochemical basis behind defects that cause the break down of the neuronal circuits and ultimately visual impairment. Our investigations are also critical in designing innovative therapeutic approaches in treating these neuronal degenerations.

Techniques Used in the Laboratory: Cloning, expression and purification of proteins in bacteria, insect and human cells; Creation of transgenic and knock out mouse models of disease; Analyses of protein complexes by immunoprecipitation, liquid chromatography and mass-spectrometry; protein localization by in-situs, confocal immunofluorscence and electron microscopy; Electrophysiology; Synthesis, folding and assembly of proteins studied by pulse-label, pulse-chase and immunoprecipitation; Protein structure-function relationship.

Keywords: Neuronal degeneration, Childhood Blindness, Congenital Stationary Night Blindness, Signal processing from retina to brain, Synaptic transmission, Ribbon Synpases, Visual cortex, Gene therapy, Small molecule therapy, Posttranslational modifcation of proteins and protein assembly

Protein trafficking in neurons

Proteins move at the rate of 1000 molecules per second in photoreceptor cells between different compartments. Defects in this process lead to blindness in humans. How do proteins move at this rapid rate? How are proteins retained in different compartments? We are currently testing our hypothesis that small GTPases play an important role in regulating protein trafficking between different regions of photoreceptor cells.

Protein assembly and function

How do multimeric proteins assemble? We use phosphodiesterase-6 as a model system to understand protein assembly. We believe protein-lipid modification contributes to this process and are currently testing this hypothesis.

Treatment(s) for neurodegenerative diseases

We used adeno-associated viral mediated gene therapy to restore vision in a mouse model for severe childhood blindness. We hope to expand this line of research using cutting-edge genome engineering methods such as TALENs and CRISPR system for stem cell therapy.

Small molecules, translational suppressors, treatment for blindness?

As an alternative to gene therapy, we are exploring the use of small molecule translational read-through suppressors to overcome non-sense mutations that lead to diseases. This project is in collaboration with Dr. Brian Popp in the Chemistry Department.

Splicing and blinding diseases

Defects in ubiquitously expressed splicing genes are a cause of retinitis pigmentosa (RP) in humans. In collaboration with Dr. Peter Stoilov at Biochemistry, we are identifying the mechanism behind splicing defects and blindness. The hope is to use the knowledge gained in this study to design novel treatments for patients with RP.

        This project will investigate how RNA binding proteins boost protein expression in photoreceptor cells to enable vision, an unexplored aspect of the photoreceptor cell biology. Our work will allow us to better understand how photoreceptors function and how blinding disease develops. We expect that the results of this study will open new ways to treat blinding diseases