Venkata Ramana Murthy Chavali, Ph.D.

faculty photo
Research Assistant Professor of Ophthalmology
Department: Ophthalmology

Contact information
Rm.133A, Anatomy Chemistry Building, 3620 Hamilton Walk, University of Pennsylvania
Philadelphia, PA 19104
Office: 4057144198
Lab: 2158988320
Education:
B.Sc. (Biotechnology)
Andhra University, Visakhapatnam, INDIA, 1999.
M.Sc. (Biotechnology)
Andhra University, Visakhapatnam, INDIA, 2001.
PhD (Molecular Virology)
Indian Institute of Technology Kharagpur, INDIA, 2007.
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Description of Research Expertise

My lab applies multi-disciplinary approaches to studying retinal pathology in Age-related Macular Degeneration (AMD) and Primary Open Angle Glaucoma (POAG) by understanding (1) pathways associated with these pathologies caused by SNPs in genes associated with cholesterol metabolism and lipid biogenesis in AMD and POAG (2) role of non-coding RNA, differentially expressing transcriptome and eQTLs in causing retinal pathobiology, and (3) investigating the role of novel SNPs/genes associated with POAG in African-American cohorts.

Age related macular degeneration (AMD) is the most common cause of an irreversible vision loss affecting the elderly. It's a multifactorial disorder affecting individuals over 55 years of age. Dr. Chavali's lab is investigating mechanisms leading to AMD by i) investigating the role of non-coding RNA associated with AMD, ii) characterizing the lipid pathways in RPE that are responsible for the biogenesis of soft drusen, or sub-retinal drusen deposits in AMD using in vitro systems and transgenic mouse models, and, iii) Understanding the functions of AMD associated genes using CRISPR/Cas9 gene editing methodologies in human induced pluripotent stem cell- derived RPEs, human fetal RPE cultures and using animal model studies.

Over the last three years, our lab has been actively involved in the understanding the molecular pathophysiology of Primary Open-Angle Glaucoma (POAG) in African Americans in collaboration with Dr. Joan O'Brien's lab. POAG is the most common form of Glaucoma causing blindness in the elderly over 50 years of age and it affects years early and with faster progression in African Americans compared to Caucasians. The molecular characterization studies in POAG include in vitro functional characterization of POAG associated variants, transcriptome profiling of normal and POAG African American patient's iPSC-RGCs to understand POAG-associated differentially expressed genes and noncoding RNA in African Americans, single-cell transcriptome sequencing to characterize RGC subtypes in the retina, and investigating the role of mitochondrial haplogroup association with POAG.

To drive translation approaches to these blinding diseases, our lab has established in vitro models to study the developmental and blinding disorders using human induced pluripotent stem cells (iPSCs), to study how dysregulated downstream pathways are related to clinical manifestations. Our lab established novel methodologies and protocols to differentiate patient-specific pluripotent stem cells (with and without pathogenic mutations) direct them towards development of human Retinal Organoids and retinal cell types (RPE, RPC and RGC) using in vitro differentiation assays. Our goal is to identify mechanisms that may lead to a better understanding of AMD and/or POAG disease progression and new targets for therapeutic interventions.

Selected Publications

Park J, Lucas AM, Zhang X, Chaudhary K, Cho JH, Nadkarni G, Dobbyn A, Chittoor G, Josyula NS, Katz N, Breeyear JH, Ahmadmehrabi S, Drivas TG, Chavali VRM, Fasolino M, Sawada H, Daugherty A, Li Y, Zhang C, Bradford Y, Weaver J, Verma A, Judy RL, Kember RL, Overton JD, Reid JG, Ferreira MAR, Li AH, Baras A, LeMaire SA, Shen YH, Naji A, Kaestner KH, Vahedi G, Edwards TL, Chen J, Damrauer SM, Justice AE, Do R, Ritchie MD, Rader DJ.: Exome-wide evaluation of rare coding variants using electronic health records identifies new gene-phenotype associations. Nature Medicine 27: 66-72, Jan 2021.

Cole BS, Gudiseva HV, Pistilli M, Salowe R, McHugh CP, Zody MC, Chavali VRM, Ying GS, Moore JH, O'Brien JM.: The Role of Genetic Ancestry as a Risk Factor for Primary Open-angle Glaucoma in African Americans. Invest Ophthalmol Vis Sci 62: 28, Feb 2021.

Ross AG, McDougald DS, Khan RS, Duong TT, Dine KE, Aravand P, Bennett J, Chavali VRM, Shindler KS.: Rescue of retinal ganglion cells in optic nerve injury using cell-selective AAV mediated delivery of SIRT1. Gene Therapy Feb 2021.

Rathi S, Danford I, Gudiseva HV, Verkuil L, Pistilli M, Vishwakarma S, Kaur I, Dave T, O'Brien JM, Chavali VRM.: Molecular Genetics and Functional Analysis Implicate CDKN2BAS1-CDKN2B Involvement in POAG Pathogenesis. Cells 9: 1934, Aug 2020.

Chavali VRM, Haider N, Rathi S, Vrathasha V, Alapati T, He J, Gill K, Nikonov R, Duong TT, McDougald DS, Nikonov S, O'Brien J, Mills JA.: Dual SMAD inhibition and Wnt inhibition enable efficient and reproducible differentiations of induced pluripotent stem cells into retinal ganglion cells. Scientific Reports 10: 11828, Jul 2020.

Porter LF, Saptarshi N, Fang Y, Rathi S, den Hollander AI, de Jong EK, Clark SJ, Bishop PN, Olsen TW, Liloglou T, Chavali VRM, Paraoan L.: Whole-genome methylation profiling of the retinal pigment epithelium of individuals with age-related macular degeneration reveals differential methylation of the SKI, GTF2H4, and TNXB genes. Clinical Epigenetics 11: 6, Jan 2019.

Gudiseva HV, Pistilli M, Salowe R, Singh LN, Collins DW, Cole B, He J, Merriam S, Khachataryan N, Henderer J, Addis V, Cui QN, Sankar PS, Miller-Ellis E, Chavali VRM, Ying GS, Wallace D, O'Brien JM.: The association of mitochondrial DNA haplogroups with POAG in African Americans. Experimental Eye Research 181: 85-89, Apr 2019.

Verkuil L, Danford I, Pistilli M, Collins DW, Gudiseva HV, Trachtman BT, He J, Rathi S, Haider N, Ying GS, Chavali VRM, O'Brien JM.: SNP located in an AluJb repeat downstream of TMCO1, rs4657473, is protective for POAG in African Americans. Br J Ophthalmol 103: 1530-1536, Oct 2019.

Khachatryan N, Pistilli M, Maguire MG, Salowe RJ, Fertig RM, Moore T, Gudiseva HV, Chavali VRM, Collins DW, Daniel E, Murphy W, Henderer JD, Lehman A, Cui Q, Addis V, Sankar PS, Miller-Ellis EG, O'Brien JM.: Primary Open-Angle African American Glaucoma Genetics (POAAGG) Study: gender and risk of POAG in African Americans. PLoS One 14: e0218804, Aug 2019.

Sommer Jeffrey R, Chavali Venkata R M, Simpson Sean G, Ayyagari Radha, Petters Robert M: Cloning, characterization, and expression analysis of the pig (Sus scrofa) C1q tumor necrosis factor-related protein-5 gene. Molecular vision 18: 92-102, Jan 2012.

Naeem Muhammad Asif, Chavali Venkata R M, Ali Shahbaz, Iqbal Muhammad, Riazuddin Saima, Khan Shaheen N, Husnain Tayyab, Sieving Paul A, Ayyagari Radha, Riazuddin Sheikh, Hejtmancik J Fielding, Riazuddin S Amer: GNAT1 Associated with Autosomal Recessive Congenital Stationary Night Blindness. Investigative ophthalmology & visual science 53(3): 1353-61, Mar 2012.

Sinha-Datta Uma, Chavali Venkata Ramana Murthy, Ghosh Ananta K: Molecular cloning and characterization of Antheraea mylitta cytoplasmic polyhedrosis virus polyhedrin gene and its variant forms. Biochemical and biophysical research communications 332(3): 710-8, Jul 2005.

Chavali Venkata Ramana Murthy, Vasireddy Vidyullatha, Ayyagari Radha: Silencing the expression of CTRP5/C1QTNF5 and ELOVL4 genes by small interfering RNA. Advances in experimental medicine and biology. Matthew M. LaVailJohn D. AshRobert E. AndersonJoe G. HollyfieldChristian Grimm (eds.). Springer, Boston, MA, 723: 225-33, Nov 2012.

Vasireddy Vidyullatha, Chavali Venkata R M, Joseph Victory T, Kadam Rajendra, Lin Jonathan H, Jamison Jeffrey A, Kompella Uday B, Reddy Geereddy Bhanuprakash, Ayyagari Radha: Rescue of photoreceptor degeneration by curcumin in transgenic rats with P23H rhodopsin mutation. PloS one 6(6): e21193, Jun 2011.

Chavali Venkata R M, Khan Naheed W, Cukras Catherine A, Bartsch Dirk-Uwe, Jablonski Monica M, Ayyagari Radha: A CTRP5 gene S163R mutation knock-in mouse model for late-onset retinal degeneration. Human molecular genetics 20(10): 2000-14, May 2011.

Riazuddin S Amer, Shahzadi Amber, Zeitz Christina, Ahmed Zubair M, Ayyagari Radha, Chavali Venkata R M, Ponferrada Virgilio G, Audo Isabelle, Michiels Christelle, Lancelot Marie-Elise, Nasir Idrees A, Zafar Ahmad U, Khan Shaheen N, Husnain Tayyab, Jiao Xiaodong, MacDonald Ian M, Riazuddin Sheikh, Sieving Paul A, Katsanis Nicholas, Hejtmancik J Fielding: A mutation in SLC24A1 implicated in autosomal-recessive congenital stationary night blindness. American journal of human genetics 87(4): 523-31, Oct 2010.

Li Lin, Nakaya Naoki, Chavali Venkata R M, Ma Zhiwei, Jiao Xiaodong, Sieving Paul A, Riazuddin Sheikh, Tomarev Stanislav I, Ayyagari Radha, Riazuddin S Amer, Hejtmancik J Fielding: A mutation in ZNF513, a putative regulator of photoreceptor development, causes autosomal-recessive retinitis pigmentosa. American journal of human genetics 87(3): 400-9, Sep 2010.

Chavali Venkata R M, Sommer Jeffrey R, Petters Robert M, Ayyagari Radha: Identification of a promoter for the human C1Q-tumor necrosis factor-related protein-5 gene associated with late-onset retinal degeneration. Investigative ophthalmology & visual science 51(11): 5499-507, Nov 2010.

Ghorai Suvankar, Chakrabarti Mrinmay, Roy Sobhan, Chavali Venkata Ramana Murthy, Bagchi Abhisek, Ghosh Ananta Kumar: Molecular characterization of genome segment 2 encoding RNA dependent RNA polymerase of Antheraea mylitta cytoplasmic polyhedrosis virus. Virology 404(1): 21-31, Aug 2010.

Chang Bo, Mandal Md Nawajes A, Chavali Venkata R M, Hawes Norman L, Khan Naheed W, Hurd Ronald E, Smith Richard S, Davisson Muriel L, Kopplin Laura, Klein Barbara E K, Klein Ronald, Iyengar Sudha K, Heckenlively John R, Ayyagari Radha: Age-related retinal degeneration (arrd2) in a novel mouse model due to a nonsense mutation in the Mdm1 gene. Human molecular genetics 17(24): 3929-41, Dec 2008.

Chavali Venkata R M, Madhurantakam Chaithanya, Ghorai Suvankar, Roy Sobhan, Das Amit K, Ghosh Ananta K: Genome segment 6 of Antheraea mylitta cypovirus encodes a structural protein with ATPase activity. Virology 377(1): 7-18, Jul 2008.

Madhurantakam Chaithanya, Chavali Venkata Ramana Murthy, Das Amit Kumar: Analyzing the catalytic mechanism of MPtpA: a low molecular weight protein tyrosine phosphatase from Mycobacterium tuberculosis through site-directed mutagenesis. Proteins 71(2): 706-14, May 2008.

Chavali Venkata Ramana Murthy, Ghosh Ananta K: Molecular cloning, sequence analysis and expression of genome segment 7 (S7) of Antheraea mylitta cypovirus (AmCPV) that encodes a viral structural protein. Virus genes 35(2): 433-41, Oct 2007.

Cukras Catherine, Gaasterland Terry, Lee Pauline, Gudiseva Harini V, Chavali Venkata R M, Pullakhandam Raghu, Maranhao Bruno, Edsall Lee, Soares Sandra, Reddy G Bhanuprakash, Sieving Paul A, Ayyagari Radha: Exome analysis identified a novel mutation in the RBP4 gene in a consanguineous pedigree with retinal dystrophy and developmental abnormalities. PloS one 7(11): e50205, Nov 2012.

Charlson ES, Sankar PS, Miller-Ellis E, Regina M, Fertig R, Salinas J, Pistilli M, Salowe RJ, Rhodes AL, Merritt WT, Chua M, Trachtman BT, Gudiseva HV, Collins DW, Chavali VR, Nichols C, Henderer J, Ying GS, Varma R, Jorgenson E, O'Brien JM.: The Primary Open-Angle African American Glaucoma Genetics Study: Baseline Demographics. Ophthalmology 122(4): 711-20, Apr 2015.

Diniz B, Rodger D C, Chavali V R, MacKay T, Lee S Y, Stambolian D, Sadda S V R: Drusen and RPE atrophy automated quantification by optical coherence tomography in an elderly population. Eye (London, England) 29(2): 272-9, Feb 2015.

Biswas P, Chavali VRM, Agnello G, Stone E, Chakarova C, Duncan JL, Kannabiran C, Homsher M, Bhattacharya SS, Naeem MA, Kimchi A, Sharon D, Iwata T, Riazuddin S, Reddy GB, Hejtmancik JF, Georgiou G, Riazuddin SA, Ayyagari R: A missense mutation in ASRGL1 is involved in causing autosomal recessive retinal degeneration. Human molecular genetics 25(12): 2483-2497, Apr 2016.

Kim Eun Ji, Grant Gregory Robert, Bowman Anita S, Haider Naqi, Gudiseva Harini V, Chavali Venkata Ramana Murthy: Complete Transcriptome Profiling of Normal and Age-Related Macular Degeneration Eye Tissues Reveals Changes in Regulation of Non-Coding RNA and Extreme Disregulation of Anti-Sense Transcription. Scientific Reports 8(3040), Feb 2018.

David W Collins, Harini V Gudiseva, Venkata RM Chavali, Benjamin T Trachtman, Meera Ramakrishnan, William Merritt, Maxwell Pistilli, Amanda Lehman, Eydie G Miller-Ellis, Prithvi Sankar, Joan M O'Brien: Association of missense mutations in the mitochondrial MT-CO1 gene with Primary Open-Angle Glaucoma (POAG) in African-Americans. Invest Ophthalmol Vis Sci 57(12): 821, June 2016.

Shruthi Karnam, Venkata RM Chavali, G Bhanuprakash Reddy, Radha Ayyagari: Role of Complement-1q Tumor Necrosis Factor Related Protein 5 (CTRP5/C1QTNF5) in Late-Onset Retinal Degeneration (L-ORD) Pathology. Invest Ophthalmol Vis Sci 57(12): 3181, June 2016.

Venkata R M Chavali, Harini Venkata Gudiseva, Anita Bowman, David W Collins, Ahmad M Khalil, Joan M O'Brien, Dwight Stambolian: Transcriptome-wide analysis of gene expression in normal and age-related macular degeneration (AMD). Invest Ophthalmol Vis Sci 56(7): 816, June 2015.

Pooja Biswas, Venkata R M Chavali, Giulia Agnello, Jacque L Duncan, Muhammad Asif Naeem, Sheikh Riazuddin, James Fielding Hejtmancik, George Georgiou, S Amer Riazuddin, Radha Ayyagari: Identification of a mutation in ASRGL1 as the underlying cause of early-onset recessive Retinal Degeneration (RD). Invest Ophthalmol Vis Sci 56(7): 4348, June 2015.

Radha Ayyagari, Bhubanananda Sahu, Akhila Alapati, John Suk, Dirk-Uwe G Bartsch, Monica M Jablonski, Venkata R M Chavali: Presence of rd8 mutation does not effect the Lete-Onset Retinal Degeneration (L-ORD) phenotype in C57BL/6 mice with S163R Ctrp5/C1qtnf5 mutation. Invest Ophthalmol Vis Sci 56(7): 2874, June 2015.

Venkata R Chavali, Bhubanananda Sahu, Dirk-Uwe Bartsch, Tarun Bansal, Christine A Curcio, Sheldon S Miller, Monica M Jablonski, Radha Ayyagari: Absence Of Ctrp5/c1qtnf5 Leads To RPE Degeneration In Ctrp5 Gene Knock-out Mice. Invest Ophthalmol Vis Sci 53(14): 308, Jun 2012.

Radha Ayyagari, Pauline Lee, Harini V. Gudiseva, Venkata R. Chavali, Anand Patel, Ryan C. Thompson, Sandra Soares, Steven Head, Paul A. Sieving, Terry Gaasterland: Identification Of A Gene Mutation In An Arrp Family By Exome Analysis. Invest Ophthalmol Vis Sci 52(14): 5878, June 2011.

JR Sommer, VR Chavali, RM Petters, R Ayyagari: Cloning and Expression Analysis of Pig CTRP5 (Complement-1q Tumor Necrosis Factor- Related Protein 5) Gene. Invest Ophthalmol Vis Sci 50(13): 2349, June 2009.

Chekuri A, Sahu B, Chavali VRM, Voronchikhina M, Soto-Hermida A, Suk JJ, Alapati AN, Bartsch DU, Ayala-Ramirez R, Zenteno JC, Dinculescu A, Jablonski MM, Borooah S, Ayyagari R.: Long-Term Effects of Gene Therapy in a Novel Mouse Model of Human MFRP-Associated Retinopathy. Hum Gene Therapy 30: 632-650, May 2019.

Lyssenko NN, Haider N, Picataggi A, Cipollari E, Jiao W, Phillips MC, Rader DJ, Chavali VRM.: Directional ABCA1-mediated cholesterol efflux and apoB-lipoprotein secretion in the retinal pigment epithelium. Journal of Lipid Research 59: 1927-1939, Oct 2018.

Collins DW, Gudiseva HV, Chavali VRM, Trachtman B, Ramakrishnan M, Merritt WT III, Pistilli M, Rossi RA, Blachon S, Sankar PS, Miller-Ellis E, Lehman A, Addis V, O'Brien JM.: The MT-CO1 V83I Polymorphism is a Risk Factor for Primary Open-Angle Glaucoma in African American Men. Invest Ophthalmol Vis Sci 59: 1751-1759, Apr 2018.

Donita Garland, Anil Kumar Chekuri, Venkata Ramana Murthy Chavali, John Suk, Shyamanga Borooah, Radha Ayyagari: HTRA1 is increased in Bruch's membrane/choroid in a mouse model of L-ORD. Invest Ophthalmol Vis Sci 60(9): 4897, July 2019.

Venkata Ramana Murthy Chavali, Naqi Haider, Brent A Bell, Ying Song, Joshua L Dunaief: Hepatic Lipase C knockout mouse has diminished ERGs and Bruch’s lipid deposits. Invest Ophthalmol Vis Sci 60(9), July 2019.

Louise Frances Porter, Neil Saptarshi, Yongxiang Fang, Sonika Rathi, Anneke I Den Hollander, Eiko de Jong, Simon Clark, Paul N Bishop, Timothy W Olsen, Triantafillos Liloglu, Venkata Ramana Murthy Chavali, Luminita Paraoan: Whole genome methylation profiling of retinal pigment epithelium reveals differential methylation and gene expression associated with AMD. Invest Ophthalmol Vis Sci Jul 2019.

Shyamanga Borooah, Marina Voronchikhina, Anil Kumar Chekuri, Venkata Ramana Murthy Chavali, John Suk, Akhila Alapati, Dirk-Uwe G Bartsch, Naheed W Khan; Monica M Jablonski, Radha Ayyagari: Characterizing two novel mouse models of Ctrp5/C1qtnf5 to understand disease mechanism in late-onset retinal degeneration. Invest Ophthalmol Vis Sci 60(9): 5030, Jul 2019.

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Last updated: 04/14/2021
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