- Ophthalmology and Visual Sciences
Professor & Chairman
- Department of Neuroscience
- Rockefeller Neuroscience Institute
- PhD, Wesleyan University, 1998
- Dilan TL, Singh RK, Saravanan T, MOye A, Goldberg AFX, Stoilov P,Ramamurthy V (2017). Bardet–Biedl syndrome-8 (BBS8) protein is crucial for the development of outer segments in photoreceptor neurons. Hum Mol Genet, 27(2):283-294.
- Murphy D, Cieply B, Carstens R, Ramamurthy V, Stoilov P (2016). The Musashi 1 controls the splicing of photoreceptor-specific exons in the vertebrate retina. PLoS Genet, 12(8):e1006256. PMCID: PMC4991804
- Christiansen JR, Pendse ND, Kolandaivelu S, Bergo MO, Young SG, Ramamurthy V (2016). Deficiency of Isoprenylcysteine Carboxyl Methyltransferase (ICMT) leads to progressive loss of photoreceptor function. J Neurosci, 36(18):5107-14. PMCID: PMC4854971
- Murphy D, Kolandaivelu S, Ramamurthy V, Stoilov P (2016). Analysis of alternative pre-RNA splicing in the mouse retina using a fluorescent reporter. Methods Mol Biol, 1421:269-86.
- Wright ZC, Singh RK, Alpino R, Goldberg AF, Sokolov M, Ramamurthy V(2016). ARL3 regulates trafficking of prenylated phototransduction proteins to the rod outer segment. Hum Mol Genet, 25(10):2031-2044. PMCID: PMC5062590
- Murphy D, Singh R, Kolandaively S, Ramamurthy V, Stoilov P (2015). Alternative splicing shapes the phenotype of a mutation in BBS8 to cause nonsyndromic retinitis pigmentosa. Mol Cell Biol, 35(10):4860-70. PMCID: PMC4405636
- Singh RK, Kolandaivelu S, Ramamurthy V (2014). Early alteration of retinal neurons in Aipl1-/- animals. Invest Ophthalmol Vis Sci, 55(5):3081-92. PMCID: PMC4034756
- Kolandaivelu S, Ramamurthy V (2014). AIPL1 protein and its indispensable role in cone photoreceptor function and survival. Adv Exp Med Biol, 801:43-8.
- Kolandaivelu S, Singh RK, Ramamurthy V (2014). AIPL1, A protein linked to blindness, is essential for the stability of enzymes mediating cGMP metabolism in cone photoreceptor cells. Hum Mol Genet, 23(4):1002-12. PMCID: PMC3900108
- Christiansen JR, Ramamurthy V (2012). Greasing the protein trafficking machinery of photoreceptor neurons: role for post prenylation processing of proteins. Cell Logist, (2(1):15-19. PMCID: PMC3355970
- Christiansen JR, Kolandaivelu S, Bergo MO, Ramamurthy V (2011). RAS-converting enzyme 1-mediated endoproteolysis is required for trafficking of rod phosphodiesterase 6 to photoreceptor outer segments. Proc Natl Acad Sci U S A, 108(21):8862-6. PMCID: PMC3102416
- Kolandaivelu S, Chang B, Ramamurthy V (2011). Rod Phosphodiesterase-6 (PDE6) catalytic subunits restores cone function in a mouse model lacking cone PDE6 catalytic subunit. J Biol Chem, 286(38):33252-9. PMCID: PMC3190866
- Ku C*, Chiodo V, Boye S, Goldberg A, Li T, Hauswirth W, Ramamurthy V(2011). Gene therapy using self-complementary Y733F capsid mutant AAV2/8 restores vision in a model of early onset Leber congenital amaurosis. Hum Mol Genet, 20(23):4569-81. PMCID: PMC3209828
- Kirschman LT, Kolandaivelu S, Frederick JM, Dang L, Goldberg AF, Baehr W,Ramamurthy V (2010) . The Leber congenital amaurosis protein, AIPL1, is needed for the viability and functioning of cone photoreceptor cells. Hum Mol Genet, 19(6):1076-87. PMCID: PMC2830831
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.
Grants and Research
NIH R01 (2007-2016)