Gulab Zode

Picture of Gulab Zode
Professor, Ophthalmology
School of Medicine
Ph.D., University of North Texas, HSC at Fort Worth, 2008, Cell biology
Phone: (949) 824-4366
Fax: (949) 824-4366
Email: gzode@uci.edu
University of California, Irvine
334 Plumwood
Irvine, CA 92697
Research Interests
glaucoma, trabecular meshwork, retinal ganglion cells, protein misfolding, ER stress, autophagy, mitophagy, genome editing
Appointments
University of Iowa, HHMI.
Research Abstract
My laboratory is interested in understanding the pathological mechanisms involved in glaucomatous damage to trabecular meshwork (TM) and retinal ganglion cells (RGCs). Our primary focus is to understand the role of protein misfolding and its associated cellular processes including endoplasmic reticulum (ER) stress and autophagy/mitophagy in the glaucomatous TM damage and RGCs loss. Our long-term goal is to develop novel glaucoma treatment by targeting these pathologies via small molecule or genome editing methods.
Awards and Honors
2023 Alcon Senior Scientist Award from Alcon Research Institute, Fort Worth, Tx
2021 Nominated for TEMES award (recognizing outstanding researcher in Texas)
2018 Subrecipient of Lewis Rudin Glaucoma Prize
2018 Rising Star Innovation Award, University of North Texas Health Sci. Ctr.
2012 NIH Pathway to Independence Award
2011 Semifinalist for Trainee Research Award, ASHG
2011 First Prize in poster presentation, University of Iowa, IA
2007 First prize for oral presentation at Research Appreciation Day, UNTHSC
2007 Wood Balkema Memorial Travel Grant for excellence in research, UNTHSC
2007 Rachel Dauphin Memorial Scholarship for excellence in research, UNTHSC
2006 Third prize in poster presentation at Research Appreciation Day, UNTHSC
Publications
1. Patil SW, Kasetti RB, Millar JC, Zode G, A Novel Mouse Model of TGFß2-induced Ocular Hypertension using Lentiviral Gene Delivery, Int J Mol Sci. 2022 Jun 21;23(13):6883. doi: 10.3390/ijms23136883.

2. Chaudhari S, Yazdizadeh Shotorbani P, Tao Y, Kasetti R, Zode G, Mathis KW, Ma R. Neogenin pathway positively regulates fibronectin production by glomerular mesangial cells. Am J Physiol Cell Physiol. 2022 Jun 15. doi: 10.1152/ajpcell.00359.2021. Epub ahead of print. PMID: 35704698.

3. Tao Y, Chaudhari S, Shotorbani PY, Ding Y, Chen Z, Kasetti R, Zode G, Ma R. Enhanced Orai1-mediated store-operated Ca2+ channel/calpain signaling contributes to high glucose-induced podocyte injury. J Biol Chem. 2022 Apr 29;298(6):101990. doi: 10.1016/j.jbc.2022.101990. Epub ahead of print. PMID: 35490782; PMCID: PMC9136128.

4. McDowell CM, Kizhatil K, Elliott MH, Overby DR, van Batenburg-Sherwood J, Millar JC, Kuehn MH, Zode G, Acott TS, Anderson MG, Bhattacharya SK, Bertrand JA, Borras T, Bovenkamp DE, Cheng L, Danias J, De Ieso ML, Du Y, Faralli JA, Fuchshofer R, Ganapathy PS, Gong H, Herberg S, Hernandez H, Humphries P, John SWM, Kaufman PL, Keller KE, Kelley MJ, Kelly RA, Krizaj D, Kumar A, Leonard BC, Lieberman RL, Liton P, Liu Y, Liu KC, Lopez NN, Mao W, Mavlyutov T, McDonnell F, McLellan GJ, Mzyk P, Nartey A, Pasquale LR, Patel GC, Pattabiraman PP, Peters DM, Raghunathan V, Rao PV, Rayana N, Raychaudhuri U, Reina-Torres E, Ren R, Rhee D, Chowdhury UR, Samples JR, Samples EG, Sharif N, Schuman JS, Sheffield VC, Stevenson CH, Soundararajan A, Subramanian P, Sugali CK, Sun Y, Toris CB, Torrejon KY, Vahabikashi A, Vranka JA, Wang T, Willoughby CE, Xin C, Yun H, Zhang HF, Fautsch MP, Tamm ER, Clark AF, Ethier CR, Stamer WD. Consensus Recommendation for Mouse Models of Ocular Hypertension to Study Aqueous Humor Outflow and Its Mechanisms. Invest Ophthalmol Vis Sci. 2022 Feb 1;63(2):12. doi: 10.1167/iovs.63.2.12. PMID: 35129590; PMCID: PMC8842499.

5. Maddineni P, Kasetti RB, Kodati B, Yacoub S, Zode GS. Sodium 4-Phenylbutyrate Reduces Ocular Hypertension by Degrading Extracellular Matrix Deposition via Activation of MMP9. Int J Mol Sci. 2021 Sep 18;22(18):10095. doi: 10.3390/ijms221810095. PMID: 34576258; PMCID: PMC8465971.

6. Nair KS, Srivastava C, Brown RV, Koli S, Choquet H, Kang HS, Kuo YM, Grimm SA, Sutherland C, Badea A, Johnson GA, Zhao Y, Yin J, Okamoto K, Clark G, Borrás T, Zode G, Kizhatil K, Chakrabarti S, John SWM, Jorgenson E, Jetten AM. GLIS1 regulates trabecular meshwork function and intraocular pressure and is associated with glaucoma in humans. Nat Commun. 2021 Aug 12;12(1):4877. doi: 10.1038/s41467-021-25181-7. PMID: 34385434

7. Daneva Z, Marziano C, Ottolini M, Chen YL, Baker TM, Kuppusamy M, Zhang A, Ta HQ, Reagan CE, Mihalek AD, Kasetti RB, Shen Y, Isakson BE, Minshall RD, Zode GS, Goncharova EA, Laubach VE, Sonkusare SK. Caveolar peroxynitrite formation impairs endothelial TRPV4 channels and elevates pulmonary arterial pressure in pulmonary hypertension. Proc Natl Acad Sci U S A. 2021 Apr 27;118(17). doi: 10.1073/pnas.2023130118. PubMed PMID: 33879616; PubMed Central PMCID: PMC8092599

8. Patel PD, Chen YL, Kasetti RB, Maddineni P, Mayhew W, Millar JC, Ellis DZ, Sonkusare SK, Zode GS*. Impaired TRPV4-eNOS signaling in trabecular meshwork elevates intraocular pressure in glaucoma. Proc Natl Acad Sci U S A. 2021 Apr 20;118(16). doi: 10.1073/pnas.2022461118. PubMed PMID: 33853948; PubMed Central PMCID: PMC8072326.

9. Kasetti RB, Maddineni P, Kiehlbauch C, Patil S, Searby CC, Levine B, Sheffield VC, Zode GS*. Autophagy stimulation reduces ocular hypertension in a murine glaucoma model via autophagic degradation of mutant myocilin. JCI Insight. 2021 Mar 8;6(5). doi: 10.1172/jci.insight.143359. PubMed PMID: 33539326; PubMed Central PMCID: PMC8021112.

10. Maddineni P, Kasetti RB, Patel PD, Millar JC, Kiehlbauch C, Clark AF, Zode GS*. CNS axonal degeneration and transport deficits at the optic nerve head precede structural and functional loss of retinal ganglion cells in a mouse model of glaucoma. Mol Neurodegener. 2020;15(1):48. Epub 2020/08/29. doi: 10.1186/s13024-020-00400-9. PMC7457267

11. Kasetti RB, Maddineni P,Patel P, Millar JC, Searby CC, Sheffield VC and Zode GS*. ATF4 leads to glaucoma by promoting protein synthesis and ER client protein load. In press; Nature Communications 2020. doi:10.1038/s41467-020-19352-1.

12. Kasetti RB, Patel P, Maddineni P, and Zode GS*, Ex-vivo cultured human corneoscleral segment model to study the effects of glaucoma factors on trabecular meshwork. PLoS One. 2020 Jun 24;15(6):e0232111. doi: 10.1371/journal.pone.0232111. eCollection 2020. PMID: 32579557

13. Patel P, Kasetti RB, Sonkusare SK and Zode GS*, Technical brief: Direct, real-time electrochemical measurement of nitric oxide in ex vivo cultured human corneoscleral segments, Mol Vis. 2020 Jun 5;26:434-444. eCollection 2020.

14. Ottolini M, Daneva Z, Chen YL, Cope EL, Kasetti RB, Zode GS, Sonkusare SK. Mechanisms underlying selective coupling of endothelial Ca 2+ signals with eNOS vs. IK/SK channels in systemic and pulmonary arteries. J Physiol. 2020 May 28. doi: 10.1113/JP279570. Online ahead of print. PMID: 32463112

15. Edwards G, Arcuri J, Wang H, Ziebarth N, Zode G, Lee RK, Bhattacharya SK. Endogenous ocular lipids as potential modulators of intraocular pressure. J Cell Mol Med. 2020 Apr;24(7):3856-3900. doi: 10.1111/jcmm.14975. Epub 2020 Feb 23. PMID: 32090468

16. Daniel S, Renwick M, Chau VQ, Datta S, Maddineni P, Zode G, Wade EM, Robertson SP, Petroll WM, Hulleman JD. Fibulin-3 knockout mice demonstrate corneal dysfunction but maintain normal retinal integrity. J Mol Med (Berl). 2020 Nov;98(11):1639-1656. doi: 10.1007/s00109-020-01974-z. Epub 2020 Sep 22. PMID: 32964303

17. Singh PK, Kasetti RB, Zode GS, Goyal A, Juzych MS, Kumar A. Zika Virus Infects Trabecular Meshwork and Causes Trabeculitis and Glaucomatous Pathology in Mouse Eyes. mSphere. 2019 May 8;4(3). pii: e00173-19. doi: 10.1128/mSphere.00173-19. PMID:31068433

18. Kasetti RB, Maddineni P, Patel P, Millar JC, Phan TP, Searby CC, Clark AF, Sheffield VC and Zode GS*, TGFß2 signaling regulates glucocorticoid-induced ocular hypertension via induction of abnormal ECM accumulation and ER stress in the trabecular meshwork. J Biol Chem. 2018 Jun 22;293(25):9854-9868. doi: 10.1074/jbc.RA118.002540. Epub 2018 May 9.PMID:29743238

19. Keller et al., Consensus recommendations for trabecular meshwork cell isolation, characterization and culture. Exp Eye Res. 2018 Jun;171:164-173. doi: 10.1016/j.exer.2018.03.001. Epub 2018 Mar 9.PMID:29526795

20. Raghunathan VK, Benoit J, Kasetti R, Zode G, Salemi M, Phinney BS, Keller KE, Staverosky JA, Murphy CJ, Acott T, Vranka J. Glaucomatous cell derived matrices differentially modulate non-glaucomatous trabecular meshwork cellular behavior. Acta Biomater. 2018 Mar 7. pii: S1742-7061(18)30120-X. doi: 10.1016/j.actbio.2018.02.037.

21. Maddineni P, Kasetti RB, Zode GS*. Methods for Analyzing Endoplasmic Reticulum Stress in the Trabecular Meshwork of Glaucoma Models. Methods Mol Biol. 2018;1695:121-134. doi: 10.1007/978-1-4939-7407-8_12.PMID:2919002

22. Kasetti RB, Maddineni P, Millar JC, Clark AF, Zode GS*. Increased synthesis and deposition of extracellular matrix proteins leads to endoplasmic reticulum stress in the trabecular meshwork. Sci Rep-Uk. 2017;7(1):14951. doi: 10.1038/s41598-017-14938-0.

23. Jain A, Zode G*, Kasetti RB, Ran FA, Yan W, Sharma TP, Bugge K, Searby CC, Fingert JH, Zhang F, Clark AF, Sheffield VC*. CRISPR-Cas9-based treatment of myocilin-associated glaucoma. Proc Natl Acad Sci U S A. 2017. doi: 10.1073/pnas.1706193114. PubMed PMID: 28973933.

24. Patel GC, Phan TN, Maddineni P, Kasetti RB, Millar JC, Clark AF*, and Zode GS,* Dexamethasone-induced ocular hypertension in mice: Effects of myocilin and route of administration, Am J Pathol. 2017 Apr;187(4):713-723. doi: 10.1016/j.ajpath.2016.12.003. Epub 2017 Feb 4.

25. Kasetti RB, Phan TN, Millar JC, Zode GS*, Expression of Mutant Myocilin Induces Abnormal Intracellular Accumulation of Selected Extracellular Matrix Proteins in the Trabecular Meshwork Invest Ophthalmol Vis Sci. 2016 Nov 1;57(14):6058-6069. doi: 10.1167/iovs.16-19610.

26. Zadoo S, Nguyen A, Zode G, Hulleman JD. A Novel Luciferase Assay For Sensitively Monitoring Myocilin Variants in Cell Culture. Invest Ophthalmol Vis Sci. 2016 Apr 1;57(4):1939-50. doi: 10.1167/iovs.15-18789.

27. Peters JC, Bhattacharya S, Clark AF, Zode GS. Increased Endoplasmic Reticulum Stress in Human Glaucomatous Trabecular Meshwork Cells and Tissues. Invest Ophthalmol Vis Sci. 2015 Jun;56(6):3860-8. doi: 10.1167/iovs.14-16220. PubMed PMID: 26066753; PubMed Central PMCID: PMC4468426.

28. Lu W, Hu H, Sévigny J, Gabelt BT, Kaufman PL, Johnson EC, Morrison JC, Zode GS, Sheffield VC, Zhang X, Laties AM, Mitchell CH. Rat, mouse, and primate models of chronic glaucoma show sustained elevation of extracellular ATP and altered purinergic signaling in the posterior eye. Invest Ophthalmol Vis Sci. 2015 May;56(5):3075-83. doi: 10.1167/iovs.14-15891. PubMed PMID: 26024091; PubMed Central PMCID: PMC4439132.

29. Beckel JM, Argall AJ, Lim JC, Xia J, Lu W, Coffey EE, Macarak EJ, Shahidullah M, Delamere NA, Zode GS, Sheffield VC, Shestopalov VI, Laties AM, Mitchell CH. Mechanosensitive release of adenosine 5'-triphosphate through pannexin channels and mechanosensitive upregulation of pannexin channels in optic nerve head astrocytes: a mechanism for purinergic involvement in chronic strain. Glia. 2014 Sep;62(9):1486-501. doi: 10.1002/glia.22695. Epub 2014 May 19

30. Zode GS*, Sharma AB, Nishimura DY, Searby CC, Stone, E.M., and Sheffield, V.C*. Ocular-specific ER stress reduction rescues glaucoma in murine glucocorticoid-induced glaucoma. J Clin Invest. 2014 May;124(5):1956-65. Epub 2014 Apr 1.

31. Zode, G.S., Bugge, K.E., Mohan, K., Grozdanic, S.D., Peters, J.C., Koehn, D.R., Anderson, M.G., Kardon, R.H., Stone, E.M., and Sheffield, V.C. Topical ocular sodium 4-phenylbutyrate rescues glaucoma in a myocilin mouse model of primary open angle glaucoma. Invest Ophthalmol Vis Sci. 2012.

32. Zode GS, Kuehn MH, Nishimura DY, Searby CC, Mohan K, Grozdanic SD, et al. Reduction of ER stress via a chemical chaperone prevents disease phenotypes in a mouse model of primary open angle glaucoma. J Clin Invest.121(9):3542-53. PMCID: 3163970.

33. Sethi A, Jain A, Zode GS, Wordinger RJ, Clark AF. Role of TGFbeta/Smad signaling in gremlin induction of human trabecular meshwork extracellular matrix proteins. Invest Ophthalmol Vis Sci.52(8):5251-9. PMCID: 3176052.

34. Zode GS, Sethi A, Brun-Zinkernagel AM, Chang IF, Clark AF, Wordinger RJ. Transforming growth factor-beta2 increases extracellular matrix proteins in optic nerve head cells via activation of the Smad signaling pathway. Mol Vis.17:1745-58. PMCID: 3130727.

35. Zode GS, Clark AF, Wordinger RJ. Bone morphogenetic protein 4 inhibits TGF-beta2 stimulation of extracellular matrix proteins in optic nerve head cells: role of gremlin in ECM modulation. Glia. 2009;57(7):755-66.

36. Wordinger RJ, Zode G, Clark AF. Focus on molecules: gremlin. Exp Eye Res. 2008;87(2):78-79. PMCID: 2649704.

37. Zode GS, Clark AF, Wordinger RJ. Activation of the BMP canonical signaling pathway in human optic nerve head tissue and isolated optic nerve head astrocytes and lamina cribrosa cells. Invest Ophthalmol Vis Sci. 2007;48(11):5058-67.

38. Wordinger RJ, Fleenor DL, Hellberg PE, Pang IH, Tovar TO, Zode GS, et al. Effects of TGF-beta2, BMP-4, and gremlin in the trabecular meshwork: implications for glaucoma. Invest Ophthalmol Vis Sci. 2007;48(3):1191-200.
Grants
1. Non-Viral Delivery Methods of Genome Editing for the Treatment of Glaucoma: Alcon Research Institute Aug 1, 2023 - Jul 30, 2026 Role: PI 2: Development and characterization of an inducible model for myocilin POAG: NEI R21 EY034333Aug 1, 2023 - Jul 30, 2025 Role: PI 3. Impaired TRVP4-eNOS signaling in TM contributes to glaucoma: NIH R01EY034238Sep 1, 2022 - Jun 30, 2027 Role: Principal Investigator 4. Novel Genome Editing for the Treatment of Glaucoma NIH R01EY030366Jul 1, 2019 - Apr 30, 2024 Role: Principal Investigator 5.Crosstalk Between Unfolded Protein Response and Autophagy for the Treatment of Glaucoma: NIH R01EY026177Mar 1, 2016 - Apr 30, 2026 Role: Principal Investigator
Research Centers
Center for Translational Vision Research
Last updated
09/01/2023