CBGM Faculty - Dr. Ashok Sharma's Lab

Bioinformatics | Big data from tiny ocular fluids | Tear Film | Aqueous Humor | Vitreous Fluid | Biomarkers| Ocular Surface

Associate Professor
Genomic Medicine Graduate Program Director
Center for Biotechnology & Genomic Medicine
Department of Ophthalmology
Medical College of Georgia at Augusta University

706-721-6335

Education

PhD, Genomic Medicine / Bioinformatics,
Medical College of Georgia at Augusta University, Augusta, GA

Research Interests

With a background in computer science and a PhD in Genomic Medicine, I have experience in both the computational and biological aspects of biomedical research. My research focus is on the development of biologically meaningful algorithms for comprehensive analysis and the visualization of high-throughput data by incorporating biological knowledge and rigorous computational methods. In the last decade, biomedical research has been revolutionized by the advent of high-throughput technologies which can generate large amounts of data. Unlocking the meaningful biological information contained inside high-throughput data is a big challenge for bench biologists. In order to facilitate the analysis of such complex data, it is crucial to develop statistical tools as well as efficient algorithms and methods to extract useful information. My primary area of research is bioinformatics, where I apply computational, mathematical, and statistical methods to solve complex biological problems. Long term goals of my lab are to solve the challenges in the analysis of data from many high-throughput technologies, especially mass spectrometry-based proteomics, and to implement these solutions in usable software tools.

Aqueous Humor Proteomics Database

Aqueous humor (AH) is the fluid in the anterior and posterior chambers of the eye that contains proteins regulating many ocular health functions, including nutrient and oxygen supply, the removal of metabolic waste, ocular immunity, and ocular shape and refraction. The dynamics of AH and the fine balance between production and drainage is essential in maintaining the physiological intraocular pressure (IOP). Therefore, identifying the protein contents of AH is vital in understanding their physiological and pathological roles in the eye.

By utilizing a large sample set, state of the art technology, and revolutionary data analysis methods, we identified the constitutive proteome of human aqueous humor, which may be useful as a reference for future studies. Discovery of AH proteomic alterations associated with glaucomatous optic neuropathy and glaucoma risk factors will help the research community at large in understanding physiological and pathological proteomics signatures in the AH.

Website: https://ahp.augusta.edu/

Tear fluid biomarkers

The tear film is a thin (2-6 µm) multi-layer fluid that coats the corneal and conjunctival epithelia. The proximity of the tear film to the ocular milieu, the non-invasive nature of its collection and its high protein concentration make it an attractive source for proteomic biomarker studies. We have developed a new workflow for proteomic analysis of tear fluid samples obtained with Schirmer strips that can identify over 3000 proteins in tear samples from human subjects.

We plan to collect a large number of tear samples using a standardized method and then, develop a reference tear proteomic database to prioritize, integrate, and analyze potential biomarkers. This will provide a readily accessible and permanent resource, fostering collaboration between laboratories to expand and improve the database. It is also likely that this database will help the vision research community to understand the physiological and pathological proteomic signatures in tear fluid.

Small non-coding RNAs

Small non-coding RNAs (sncRNAs) are diverse RNA molecules with potential applications as biomarkers and therapeutic targets in various diseases due to their role in gene expression regulation. Subtypes, including microRNA (miRNA), small nucleolar RNA (snoRNA), small nuclear RNA (snRNA), and transfer RNA (tRNA), have distinct functions and lengths. Recent research highlights the presence of extracellular RNA in human tears, showing altered sncRNA levels in ocular disorders (e.g., diabetic retinopathy, glaucoma, and DED) and non-ocular diseases (e.g., Alzheimer’s disease, breast cancer). Despite being in its early stages, this project aims to bridge the knowledge gap by leveraging advanced technologies and software to analyze tear sncRNAs. The findings will lay the groundwork for future studies using tear biomarkers to enhance diagnostic methods.

Bioinformatics Support

I work with an interdisciplinary team to carry out bioinformatics analysis and to pursue research projects in collaboration with other biologists. Currently, I am developing analytical methods for the large-scale measurements that are part of several Cancer and Diabetes projects. In our center (CBGM: Center for Biotechnology and Genomic Medicine), I am providing bioinformatics support for several long-term studies including The Environmental Determinants of Diabetes in the Young (TEDDY), the Phenome and Genome of Diabetes Autoimmunity (PAGODA), the Diabetic Complications Consortium (DiaComp), the Mouse Metabolic Phenotype Consortium (MMPC) and Biomarkers and Therapeutics in Cancer (BAT Cancer).

Protein Mass Spectrometry Analyses

Bottom-up Proteomics
Top-Down Proteomics
Targeted Quantitation
Post Translational Modification Analysis: Glycosylation and Phosphorylation
Glycan Identification & Characterization

Vision Research Projects

Identification of Tear Film Proteomic Biomarkers for Dry Eye Disease
Proteomic Biomarkers for Glaucomatous Optic Neuropathy
Targeting Interleukin-6 Trans-signaling in Diabetic Retinopathy
Proteomic, Glycomic, and Glycoproteomic Profiling in Patients with Diabetic Retinopathy
Unraveling the role of genetics in the pathogenesis of diabetic retinopathy

Media articles

Noninvasive technique collects sufficient tear fluid to look for biomarkers of health and disease | National Eye Institute (nih.gov)

Eurekalert (Jan 17, 2018)

New technology enables identification of biomarkers for a wide range of diseases

Genetic discovery may help better identify children at risk for type 1 diabetes

Powerful anti-inflammatory molecule may block vision loss in diabetic retinopathy

Tag Archives: Ashok Sharma

Publications

Complete List of Published Work in MyBibliography:
https://www.ncbi.nlm.nih.gov/myncbi/ashok.sharma.1/bibliography/public/

Selected publications:

Lee TJ, Goyal A, Jones G, Glass J, Doshi V, Bollinger K, Ulrich L, Ahmed S, Kodeboyina SK, Estes A, Töteberg-Harms M, Zhi W, Sharma S, Sharma A. AHP DB: a reference database of proteins in the human aqueous humor. Database (Oxford). 2024 Jan 29;2024. doi: 10.1093/database/baae001. PubMed PMID: 38284936; PubMed Central PMCID: PMC10878049.

Jones G, Altman J, Ahmed S, Lee TJ, Zhi W, Sharma S, Sharma A. Unraveling the Intraday Variations in the Tear Fluid Proteome. Invest Ophthalmol Vis Sci. 2024 Mar 5;65(3):2. doi: 10.1167/iovs.65.3.2. PubMed PMID: 38441890; PubMed Central PMCID: PMC10916888.

Beisel A, Jones G, Glass J, Lee TJ, Töteberg-Harms M, Estes A, Ulrich L, Bollinger K, Sharma S, Sharma A. Comparative analysis of human tear fluid and aqueous humor proteomes. Ocul Surf. 2024 Mar 30;. doi: 10.1016/j.jtos.2024.03.011. [Epub ahead of print] PubMed PMID: 38561100.

Ahmad Z, Singh S, Lee TJ, Sharma A, Lydic TA, Giri S, Kumar A. Untargeted and temporal analysis of retinal lipidome in bacterial endophthalmitis. Prostaglandins Other Lipid Mediat. 2024 Apr;171:106806. doi: 10.1016/j.prostaglandins.2023.106806. Epub 2024 Jan 5. Review. PubMed PMID: 38185280; PubMed Central PMCID: PMC10939753.

Lee H, Lee TJ, Galloway CA, Zhi W, Xiao W, de Mesy Bentley KL, Sharma A, Teng Y, Sesaki H, Yoon Y. The mitochondrial fusion protein OPA1 is dispensable in the liver and its absence induces mitohormesis to protect liver from drug-induced injury. Nat Commun. 2023 Oct 23;14(1):6721. doi: 10.1038/s41467-023-42564-0. PubMed PMID: 37872238; PubMed Central PMCID: PMC10593833.

Vashishtha A, Maina SW, Altman J, Jones G, Lee TJ, Bollinger KE, Ulrich L, Töteberg-Harms M, Estes AJ, Zhi W, Sharma S, Sharma A. Complement System Proteins in the Human Aqueous Humor and Their Association with Primary Open-Angle Glaucoma. J Pers Med. 2023 Sep 19;13(9). doi: 10.3390/jpm13091400. PubMed PMID: 37763167; PubMed Central PMCID: PMC10532607.

Altman J, Jones G, Ahmed S, Sharma S, Sharma A. Tear Film MicroRNAs as Potential Biomarkers: A Review. Int J Mol Sci. 2023 Feb 12;24(4). doi: 10.3390/ijms24043694. Review. PubMed PMID: 36835108; PubMed Central PMCID: PMC9962948.

Jones G, Lee TJ, Glass J, Rountree G, Ulrich L, Estes A, Sezer M, Zhi W, Sharma S, Sharma A. Comparison of Different Mass Spectrometry Workflows for the Proteomic Analysis of Tear Fluid. Int J Mol Sci. 2022 Feb 19;23(4). doi: 10.3390/ijms23042307. PubMed PMID: 35216421; PubMed Central PMCID: PMC8875482.

Patel PA, Lee TJ, Kodeboyina SK, Jones G, Bollinger K, Ulrich L, Bogorad D, Estes A, Zhi W, Sharma S, Sharma A. Intra-population differences of apolipoproteins in the aqueous humor. Lipids Health Dis. 2021 Oct 3;20(1):128. doi: 10.1186/s12944-021-01555-0. PubMed PMID: 34602085; PubMed Central PMCID: PMC8487476.

Kodeboyina SK, Lee TJ, Bollinger K, Ulrich L, Bogorad D, Estes A, Zhi W, Sharma S, Sharma A. Aqueous Humor Proteomic Alterations Associated with Visual Field Index Parameters in Glaucoma Patients: A Pilot Study. J Clin Med. 2021 Mar 12;10(6):1180.

Robinson R, Brown D, Churchwell L, Lee TJ, Kodeboyina SK, Bloom J, Sharma A, Sharma S. RNA-Seq analysis reveals gene expression changes induced by IL-6 trans-signaling activation in retinal endothelial cells. Cytokine. 2021 Mar;139:155375.

Kolhe R, Owens V, Sharma A, Lee TJ, Zhi W, Ghilzai U, Mondal AK, Liu Y, Isales CM, Hamrick MW, Hunter M, Fulzele S. Sex-Specific Differences in Extracellular Vesicle Protein Cargo in Synovial Fluid of Patients with Osteoarthritis. Life (Basel). 2020 Dec 10;10(12):337.

Kodeboyina SK, Lee TJ, Churchwell L, Ulrich L, Bollinger K, Bogorad D, Estes A, Zhi W, Sharma S, Sharma A. The Constitutive Proteome of Human Aqueous Humor and Race Specific Alterations. Proteomes. 2020 Nov 18;8(4):34.

Sharma A, Cox J, Glass J, Lee TJ, Kodeboyina SK, Zhi W, Ulrich L, Lukowski Z, Sharma S. Serum Glycoproteomic Alterations in Patients with Diabetic Retinopathy. Proteomes. 2020 Sep 13;8(3):25.

Robinson R, Youngblood H, Iyer H, Bloom J, Lee TJ, Chang L, Lukowski Z, Zhi W, Sharma A, Sharma S. Diabetes Induced Alterations in Murine Vitreous Proteome Are Mitigated by IL-6 Trans-Signaling Inhibition. Invest Ophthalmol Vis Sci. 2020 Sep 1;61(11):2.

Robinson R, Srinivasan M, Shanmugam A, Ward A, Ganapathy V, Bloom J, Sharma A, Sharma S. Interleukin-6 trans-signaling inhibition prevents oxidative stress in a mouse model of early diabetic retinopathy. Redox Biol. 2020 Jul;34:101574.

Fulzele S, Sahay B, Yusufu I, Lee TJ, Sharma A, Kolhe R, Isales CM. COVID-19 Virulence in Aged Patients Might Be Impacted by the Host Cellular MicroRNAs Abundance/Profile. Aging Dis. 2020 May 9;11(3):509-522.

Vashishtha A, Lee TJ, Sharma A, Wallbillich JJ. Changes in microRNA expression associated with metastasis and survival in patients with uveal melanoma. Oncotarget. 2020 Apr 21;11(16):1435-1447.

Youngblood H, Robinson R, Sharma A, Sharma S. Proteomic Biomarkers of Retinal Inflammation in Diabetic Retinopathy. International Journal of Molecular Sciences Int J Mol Sci. 2019 Sep 25;20(19).

Zhu H, Bhatt B, Sivaprakasam S, Cai Y, Liu S, Kodeboyina S, Patel N, Savage N, Sharma A, Kaufman R, Li H, and Singh N. Ufbp1 promotes plasma cell development and ER expansion by modulating distinct branches of UPR. Nature Communications, 2019 Mar 6; 10(1):1084.

Sharma A, Valle ML, Beveridge C, Liu Y, Sharma S. Unraveling the role of genetics in the pathogenesis of diabetic retinopathy. Eye (Lond). 2019.

Valle ML, Dworshak J, Sharma A, Ibrahim AS, Al-Shabrawey M, Sharma S.Inhibition of interleukin-6 trans-signaling prevents inflammation and endothelial barrier disruption in retinal endothelial cells. Exp Eye Res. 2019; 178:27-36.

Dimri M, Humphries A, Laknaur A, Elattar S, Lee TJ, Sharma A, Kolhe R, Satyanarayana A. Nqo1 ablation inhibits activation of the PI3K/Akt and MAPK/ERK pathways and blocks metabolic adaptation in hepatocellular carcinoma. Hepatology 2019.

Sharma S, Bollinger KE, Kodeboyina SK, Zhi W, Patton J, Bai S, Edwards B, Ulrich L, Bogorad D, Sharma A*. A. Proteomic Alterations in Aqueous Humor from Patients with Primary Open Angle Glaucoma. Invest Ophthalmol. Vis. Science (IOVS). 2018 April

Purohit S, Li T, Guan W, Song X, Song J, Tian Y, Li L, Sharma A, Dun B, Mysona D, Ghamande S, Rungruang B, Cummings RD, Wang PG, She JX. Multiplex glycan bead array for high throughput and high content analyses of glycan binding proteins. Nature Communications. 2018 Jan 17;9(1):258.

Sharma A, Liu X, Hadley D, Hagopian W, Chen WM, Onengut-Gumuscu S, Törn C, Steck AK, Frohnert BI, Rewers M, Ziegler AG, Lernmark Å, Toppari J, Krischer JP, Akolkar B, Rich SS, She JX; TEDDY Study Group. Identification of non-HLA genes associated with development of islet autoimmunity and type 1 diabetes in the prospective TEDDY cohort. Journal of Autoimmunity. 2018 Jan 5.

Törn C, Liu X, Hagopian W, Lernmark Å, Simell O, Rewers M, Ziegler AG, Schatz D, Akolkar B, Onengut-Gumuscu S, Chen WM, Toppari J, Mykkänen J, Ilonen J, Rich SS, She JX, Sharma A, Steck A, Krischer J; TEDDY Study Group. Complement gene variants in relation to autoantibodies to beta cell specific antigens and type 1 diabetes in the TEDDY Study. Sci Rep. 2016 Jun 16; 6:27887.

Sharma A, Liu X, Hadley D, Hagopian W, Liu E, Chen WM, Onengut-Gumuscu S, Simell V, Rewers M, Ziegler AG, Lernmark Å, Simell O, Toppari J, Krischer JP, Akolkar B, Rich SS, Agardh D, She JX. Identification of Non-HLA Genes Associated with Celiac Disease and Country-Specific Differences in a Large, International Pediatric Cohort. PloS one. 2016 Mar 25; 11(3):e0152476.

Lavoie TN, Carcamo WC, Wanchoo A, Sharma A, Gulec A, Berg KM, Stewart CM, Nguyen CQ. IL-22 regulation of functional gene expression in salivary gland cells. Genomics data. 2016 Mar; 7:178-84.

Sharma A^¶, Purohit S^¶, Sharma S, Bai S, Zhi W, Ponny SR, Hopkins D, Steed L, Bode B, Anderson SW, She JX. IGF-binding proteins in type 1 diabetes are more severely altered in the presence of complications. Frontiers in endocrinology. 2016 Jan 29; 7:2.

Purohit S^¶, Sharma A^¶, Hopkins D, Steed L, Bode B, Anderson SW, Reed JC, Steed RD, Yang T, She JX. Large scale discovery and validation studies demonstrate significant reductions in circulating levels of IL8, IL-1Ra, MCP-1 and MIP-1β in type-1 diabetes patients. J Clin Endocrinol Metab 2015 Sep; 100(9):E1179-87.

Sharma S, Purohit S, Sharma A, Hopkins D, Steed L, Bode B, Anderson SW, Caldwell R, She JX. Elevated Serum Levels of Soluble TNF Receptors and Adhesion Molecules Are Associated with Diabetic Retinopathy in Patients with Type-1 Diabetes. Mediators of Inflammation. 2015

Purohit S, Sharma A, She JX. Luminex and Other Multiplex High Throughput Technologies for the Identification of, and Host Response to, Environmental Triggers of Type 1 Diabetes. BioMed Research International 2015

Jin Y, Sharma A,Bai S, Davis C, Liu H, Hopkins D, Barriga K, Rewers M, She JX.
Risk of type 1 diabetes progression in islet autoantibody-positive children can be further stratified using expression patterns of multiple genes implicated inperipheral blood lymphocyte activation and function.Diabetes. 2014Jul;63(7):2506-15. doi: 10.2337/db13-1716. Epub 2014 Mar 4.

Jin Y*, Sharma A*, Carey C*, Hopkins D, Wang X, Robertson DG, Bode B, Anderson SW, Reed JC, Steed RD, Steed L, She JX.
The expression of inflammatory genes is upregulated in peripheral blood of patients with type 1 Diabetes. Diabetes Care, 36:1–9, 2013.