Jianhai Du, PhD

Assistant Professor

Organization:

West Virginia University School of Medicine

Department:

Ophthalmology and Visual Sciences

Classification:

Faculty

Assistant Professor

Organization:

West Virginia University School of Medicine

Department:

Biochemistry

Classification:

Adjunct Faculty

• PhD, Peking University, 2006

2021

71. Sokolov D, Sechrest ER, Wang Y, Nevin C, Du J, Kolandaivelu S. Nuclear NAD+-biosynthetic enzyme NMNAT1 facilitates development and early survival of retinal neurons. Elife. 2021 Dec 8;10:e71185. doi: 10.7554/eLife.71185. Online ahead of print. PMID: 34878972.

70. Cleghorn WM, Burrell AL, Giarmarco MM, Brock DC, Wang Y, Chambers ZS, Du J, Kollman JM, Brockerhoff SE. A highly conserved zebrafish IMPDH retinal isoform produces the majority of guanine and forms dynamic protein filaments in photoreceptor cells. J Biol Chem. 2021 Nov 20:101441. doi: 10.1016/j.jbc.2021.101441. Online ahead of print. PMID: 34813793.

69. Brown EE, Scandura MJ, Mehrotra S, Wang Y, Du J, Pierce EA. Reduced nuclear NAD+ drives DNA damage and subsequent immune activation in the retina. Hum Mol Genet. 2021 Nov 8:ddab324. doi: 10.1093/hmg/ddab324. PMID: 34750622

68.  Du J, Zhu S, Lim RR, Chao JR. Proline metabolism and transport in retinal health and disease. Amino Acids. 2021 Apr 19. doi: 10.1007/s00726-021-02981-1. Online ahead of print.
PMID: 33871679. 

67. Shen W, Lee SR, Mathai AE, Zhang R, Du J, Yam MX, Pye V, Barnett NL, Rayner CL, Zhu L, Hurley JB, Seth P, Hirabayashi Y, Furuya S, Gillies MC. Effect of selectively knocking down key metabolic genes in Müller glia on photoreceptor health. Glia. 2021 Apr 9. doi: 10.1002/glia.24005. Online ahead of print. PMID: 33835598.

66. Greenwald SH, Brown EE, Scandura MJ, Hennessey E, Farmer R, Du J, Wang Y, Pierce EA. Mutant NMNAT1 leads to a retina-specific decrease of NAD+ accompanied by increased poly(ADP-ribose) in a mouse model of NMNAT1-associated retinal degeneration. Hum Mol Genet. 2021 Mar 11:ddab070. doi: 10.1093/hmg/ddab070. PMID: 33709122.

65. Xu R, Wang Y and Du J. Tracing Nitrogen Metabolism in Mouse Tissues with Gas Chromatography-Mass Spectrometry . Bio-protocol. 2021; 11(4): e3925. DOI: 10.21769/BioProtoc.3925.

64. Engel AL, Wang Y, Khuu TH, Worrall E, Manson MA, Knight K, Yanagida A, Qi JH, Ramakrishnan A, Weleber RG, Klein ML, Wilson DJ, Anand-Apte B, Hurley JB, Du J, Chao JR. Extracellular Matrix Dysfunction in Sorsby Patient-Derived Retinal Pigment Epithelium. bioRxiv doi: https://doi.org/10.1101/2021.01.06.425613

63. Sinha T, Du J, Makia MS, Hurley JB, Naash MI, Al-Ubaidi MR. Absence of retbindin blocks glycolytic flux, disrupts metabolic homeostasis, and leads to photoreceptor degeneration. Proc Natl Acad Sci U S A. 2021 Feb 9;118(6):e2018956118. PMID: 33526685

62. Zhang R, Engel AL, Wang Y, Li B, Shen W, Gillies MC, Chao JR, Du J. Inhibition of Mitochondrial Respiration Impairs Nutrient Consumption and Metabolite Transport in Human Retinal Pigment Epithelium. J Proteome Res. 2021 Jan 1;20(1):909-922. PMID: 32975122

2020

61. Xu L, Brown EE, Keuthan CJ, Gubbi H, Swaroop A, Grellier EK, Roger JE, Du J,  Ash JD. AMP-activated-kinase (AMPK) is essential sensor and metabolic regulator of retinal neurons and their integrated metabolism with RPE. bioRxiv 2020.05.22.109165; doi: https://doi.org/10.1101/2020.05.22.109165.

60. Xanthine Oxidase Drives Hemolysis and Vascular Malfunction in Sickle Cell Disease. Schmidt HM, Wood KC, Lewis SE, Hahn SA, Williams XM, McMahon B, Baust JJ, Yuan S, Bachman TN, Wang Y, Oh JY, Ghosh S, Ofori-Acquah SF, Lebensburger JD, Patel RP, Du J, Vitturi DA, Kelley EE, Straub AC. Arterioscler Thromb Vasc Biol. 2020 Dec 3:ATVBAHA120315081. doi: 10.1161/ATVBAHA.120.315081. Online ahead of print. PMID: 33267657.

59. Li B,  Zhang T, Liu W, Wang Y, Xu R, Zeng S, Zhang R, Zhu S, Gillies MC, Zhu L, Du J. Metabolic features of mouse and human retinas: rods vs. cones, macula vs. periphery, retina vs. RPE. iScience. 2020 Oct 14;23(11):101672. doi: 10.1016/j.isci.2020.101672. eCollection 2020 Nov 20. PMID: 33196018.

58. Zhang R, Shen W, Du J, Gillies MC. Selective knockdown of hexokinase 2 in rods leads to age-related photoreceptor degeneration and retinal metabolic remodeling. Cell Death & Disease. 2020. Oct 20; 885 (11). https://doi.org/10.1038/s41419-020-03103-7. PMID: 33082308.

57. Huang J, Schaefer J, Wang Y, Gioiac L, Pei Y, Shi X, Waris S, Zhao C, Nguyen J, Du J. Metabolic signature of eyelid basal cell carcinoma. Exp Eye Res.  2020 Jul 7:108140. doi: 10.1016/j.exer.2020.108140. [Epub ahead of print]. PMID: 32649951.

56. Xu R, Ritz BK, Wang Y, Huang J, Zhao C, Gong K, Liu X, Du J. The retina and retinal pigment epithelium differ in nitrogen metabolism and are metabolically connected. J Biol Chem. 2020 Jan 17. pii: jbc.RA119.011727. doi: 10.1074/jbc.RA119.011727. [Epub ahead of print]. PMID: 31953322

2019

55. Wang W, Kini A, Wang Y, Liu T, Chen Y, Vukmanic E, Emery D, Liu Y, Lu X, Jin L, Lee SJ, Scott P, Liu X, Dean K, Lu Q, Fortuny E, James R, Kaplan HJ, Du J, Dean DC.Metabolic Deregulation of the Blood-Outer Retinal Barrier in Retinitis Pigmentosa. Cell Rep. 2019 Jul 30;28(5):1323-1334.e4. PMID:31365873

54.Yam M, Engel AL , Wang Y, Zhu S, Hauer A, Zhang R, Lohner D, Huang J, Dinterman M, Zhao C, Chao JR, Du J. Proline mediates metabolic communication between retinal pigment epithelial cells and the retina. J Biol Chem. 2019. doi: 10.1074/jbc.RA119.007983. PMID:31110046. (WVU News)

53. Zhang T, Zhu L, Madigan MC, Liu W, Shen W, Cherepanoff S, Zhou F, Zeng S, Du J, Gillies MC.Human macular Müller cells rely more on serine biosynthesis to combat oxidative stress than those from the periphery. Elife. 2019 Apr 30;8. pii: e43598. doi: 10.7554/eLife.43598. PMID:31036157

52. Harmon DB, Mandler K, Sipula I, Dedousis N, Lewis SE, Eckels JT, Du J, Wang Y, Pagano PJ, Ciefuentes-Pagano E, Homanics GE, Van’t Erve TJ, Jurzcak M, O’Doherty RM,  Kelley EE. Hepatic-Specific Ablation or Whole Body Inhibition of Xanthine Oxidase in Obese Mice Corrects Systemic Hyperuricemia Without Improving the Metabolic Abnormalities. Diabetes, 2019 Apr 1. pii: db181198. doi: 10.2337/db18-1198. PMID: 30936145.

51. Grenell A, Wang Y,  Yam M, Swarup A,  Dilan T, Hauer A,  Linton J, Philp N, Gregor E,  Zhu S,  Shi Q,  Murphy J,  Guan T, Lohner D, Kolandaivelu S,  Ramamurthy V,Goldberg A, Hurley JB ,  Du J. Loss of MPC1 reprograms retinal metabolism to impair visual function. Proc Natl Acad Sci U S A., 2019 116 (9) 3530-3535. PMID: 30808746.   (News report ).

50.  Huang J, Gu S, Chen M,  Zhang SJ,  Jiang Z, Chen X,  Jiang C, Liu G,  Radu RA,  Sun X,  Vollrath D,  Du J,  Yan B,  Zhao C. Abnormal mTORC1 signaling leads to retinal pigment epithelium degeneration. Theranostics. 2019; 9(4):1170-1180.  PMID: 30867823.

49. Swarup A, Samuels IS, Bell BA, Han JYS, Du J, Massenzio E, Abel ED, Boesze-Battaglia K, Peachey NS, Philp NJ. Modulating GLUT1 expression in the RPE decreases glucose levels in the retina: Impact on photoreceptors and Müller glial cells. Am J Physiol Cell Physiol. 2019; 316(1):C121-C133. PMID: 30462537.

2018

48. Al-Ubaidi M, Du J, Naash M, Makia M, Sinha T. Flavin homeostasis in the mouse retina during aging and degeneration. J Nutr Biochem. 2018; 62:123-133. PMID: 30172221.

47. Wang Y, Grenell A, Zhong F, Yam M, Gregor E, Zhu S, Lohner D, Zhu JJ,  Du J. Metabolic signature of the aging eye in mice. Neurobiol Aging. 2018; 71:223-233.  PMID: 30172221

46. Zhu S, Yam M, Wang Y, Linton JD, Grenell A, Hurley JB, Du J. Impact of euthanasia, dissection and postmortem delay on metabolic profile in mouse retina and RPE/choroid. Exp Eye Res. 2018;174:113-120.  PMID: 29864440. [Full Text]

45. Du J, An J, Linton JD, Wang Y, Hurley JB. How Excessive cGMP Impacts Metabolic Proteins in Retinas at the Onset of Degeneration. Adv Exp Med Biol. 2018;1074:289-295. PMID: 29721955.

44. Swarup A, Bell BA, Du J, Han JYS, Soto J, Abel ED, Bravo-Nuevo A, FitzGerald PG, Peachey NS, Philp NJ.Deletion of GLUT1 in mouse lens epithelium leads to cataract formation.Exp Eye Res. 2018; 172:45-53. PMID:29604281

43. Zhang T, Gillies MC, Madigan MC, Shen W, Du J, Grünert U, Zhou F, Yam M, Zhu L. Disruption of De Novo Serine Synthesis in Müller Cells Induced Mitochondrial Dysfunction and Aggravated Oxidative Damage. Mol Neurobiol. 2018; 55(8):7025-7037. PMID:29383682.

2017

42. Kanow MA, Giarmarco MM, Jankowski CS, Tsantilas K, Engel AL, Du J, Linton JD, Farnsworth CC, Sloat SR, Rountree A, Sweet IR, Lindsay KJ, Parker ED, Brockerhoff SE, Sadilek M, Chao JR, Hurley JB. Biochemical adaptations of the retina and retinal pigment epithelium support a metabolic ecosystem in the vertebrate eye.  Elife. 2017; 6. pii: e28899. doi: 10.7554/eLife.28899.

41. Chao JR, Knight K, Engel AL, Jankowski C, Wang Y, Manson MA, Gu H, Djukovic D, Raftery D, Hurley JB, Du J. Human Retinal Pigment Epithelium Cells prefer proline as a nutrient and transport metabolic intermediates to the retinal side. J Biol Chem. 2017;292(31):12895-12905.  [Full Text]

2016

40. Du J*, Yanagida A, Knight K, Engel AL, Vo AH, Jankowski C, Sadilek M, Tran VT, Manson MA, Ramakrishnan A, Hurley JB, Chao JR*. Reductive carboxylation is a major metabolic pathway in the retinal pigment epithelium. Proc Natl Acad Sci U S A. 2016; 113(51):14710-14715.  *Corresponding Author. [Full Text]

39. Gu H, Carroll PA, Du J, Zhu J, Neto FC, Eisenman RN, Raftery D.Quantitative Method to Investigate the Balance between Metabolism and Proteome Biomass: Starting from Glycine. Angew Chem Int Ed Engl. 2016; 55(50):15646-15650.

37. Contreras L, Ramirez L, Du J, Hurley JB,  Satrústegui J, Villa P Deficient glucose and glutamine metabolism in Aralar/AGC1/Slc25a12 knockout mice contributes to altered visual function. Molecular Vision. 2016; 22:1198-1212.

36. Wu HE, Baumgardt SL, Fang J, Paterson M, Liu Y, Du J, Shi Y, Qiao S, Bosnjak ZJ, Warltier DC, Kersten JR, Ge ZD.Cardiomyocyte GTP Cyclohydrolase 1 Protects the Heart Against Diabetic Cardiomyopathy. Sci Rep. 2016; 6:27925.

35. Du J, Rountree A, Lindsay K, Sadilek M, Gu H, Djukovic D, Raftery D, Contreras L, Satrústegui J, Kanow M, Sweet IR, Hurley JB. Phototransduction regulates retinal energy metabolism. J Biol Chem. 2016; 291(9):4698-710.

2015

34. Du J, Linton JD, Hurley JB. Probing metabolism in the intact retina using stable isotope tracers Methods in Enzymology. 2015; 561:149-70. [Full Text]

33. Hurley JB, Lindsay KJ, Du J. Glucose, Lactate and shuttling of metabolites in the vertebrate retina. J Neurosci Res. 2015; 93(7):1079-92 015.

32. Gu H, Du J, Carnevale Neto F, Carroll PA, Turner SJ, Chiorean EG, Eisenman RN, Raftery D. Metabolomics method to comprehensively analyze amino acids in different domains. Analyst. 2015;140(8):2726-34.

31. Carroll PA, Diolaiti D, McFerrin L, Gu H, Djukovic D, Du J, Cheng PF, Anderson S, Ulrich M, Hurley JB, Raftery D, Ayer DE, Eisenman RN. Deregulated Myc Requires MondoA/Mlx for Metabolic Reprogramming and Tumorigenesis. Cancer Cell. 2015; 27(2):271-85.

2014

30. Lindsay KJ*, Du J*, Sloat SR, Contreras L, Linton JD,Turner SJ,Sadilek M, Satrustegui J,Hurley JB. Pyruvate Kinase and Aspartate-Glutamate Carrier Distributions Reveal Key Metabolic Links Between Neurons and Glia in Retina. Proc Natl Acad Sci U S A. . 2014;111(43):15579-84.  *First Author.

29. Hurley JB, Chertov AO, Lindsay K, Giamarco M, Cleghorn W, Du J, Brockerhoff SE. Energy metabolism in the vertebrate retina. “Vertebrate Photoreceptors: Functional Molecular Bases” edited by Furukawa T, Hurley JB and Kawamura S. 2014. 91-137. Springer. (Book Chapter)

28. Adijanto J, Du J, Moffat C, Seifert E, Hurley JB, Philp NJ.The Retinal Pigment Epithelium utilizes Fatty Acids for Ketonegenesis: Implications for Metabolic Coupling with the Outer Retina. J Biol Chem.  2014;289(30):20570-82.

2013

27. Du J, Cleghorn W, Contreras L, Linton J, Chan GC, Chertov AO, Saheki T, Govarindaju V, Sadilek M, Satrustegui J, Hurley JB. Cytosolic Reducing Power Preserves Glutamate in Retina. Proc Natl Acad Sci U S A. 2013; 288(50):36129-40.

26. Du J, Cleghorn W, Contreras L, Lindsay K, Rountree AM, Chertov AO, Turner SJ, Sahaboglu A, Linton J, Sadilek M, Sartrústegui J, Sweet IR, Paquet-Durand F,. Hurley JB. Inhibition of mitochondrial pyruvate transport by Zaprinast causes massive accumulation of aspartate at the expense of glutamate. J Biol Chem. 2013; 110(46):18501-6. [Full Text]

25. Du J*, Li Z, Li Q, Guan T, Yang Q, Xu H, Pritchard KA Jr., Camara AK, Shi Y*. Enoyl CoA Hydratase Domain-Containing 2, a Potential Novel Regulator of Myocardial Ischemia Injury. J Am Heart Assoc. 2013; 2(5):e000233. *Corresponding Author.

24. Zhang H, Jing X, Shi Y, Xu H, Du J, Guan T, Weihrauch D, Jones DW, Wang W, Gourlay D, Oldham KT, Hillery CA, Pritchard KA Jr. N-Acetyl Lysyltyrosylcysteine Amide Inhibits Myeloperoxidase, a Novel Peptide Based Inhibitor. J Lipid Res. 2013; 54(11):3016-29.

23. Teng RJ, Du J, Afolayan AJ, Eis A, Shi Y, Konduri GG. AMP kinase activation improves angiogenesis in pulmonary artery endothelial cells with in utero pulmonary hypertension. Am J Physiol Lung Cell Mol Physiol. 2013; 304(1):L29-42.

2012 and before

22. Du J*, Teng RJ, Lawrence M, Guan T, Ge Y, Shi Y*. Identification of endogenous GTP cyclohydrolase I interacting proteins in rat tissues. PLOS One. 2012;7(3):e33991. *Corresponding Author. 

21. Teng RJ, Du J, Welak S, Guan T, Eis A, Shi Y, Konduri GG. Cross-Talk between NADPH Oxidase and Autophagy in Pulmonary Artery Endothelial Cells with Intrauterine Persistent Pulmonary Hypertension. Am J Physiol Lung Cell Mol Physiol. 2012; 302(7):L651-63.

 20. Du J, Teng RJ, Guan T, Eis A, Kaul S, Konduri GG, Shi Y. The Role of Autophagy in angiogenesis in Aortic Endothelial Cells. Am J Physiol Cell Physiol. 2012; 302(2):C383-91.

19. An J*, Du J*, Wei N, Guan T, Camara AK, Shi Y. Differential Sensitivity to LPS-Induced Myocardial Dysfunction in the Isolated Brown Norway and Dahl S Rat Hearts: Roles of Mitochondrial function, NFκB Activation and TNF-α Production. Shock. 2012; 37(3):325-32. * Co-first author.

18. Vladic N, Ge ZD, Leucker T, Brzezinska AK, Du JH, Shi Y, Warltier DC, Pratt PF Jr, Kersten JR. Decreased tetrahydrobiopterin and disrupted association of Hsp90 with eNOS by hyperglycemia impair myocardial ischemic preconditioning. Am J Physiol Heart Circ Physiol. 2011; 301(5):H2130-9.

17. Teng RJ, Du J, Xu H, Bakhutashvili I, Eis A, Shi Y, Pritchard KA Jr, Konduri GG. Sepiapterin improves angiogenesis of pulmonary artery endothelial cells with in utero pulmonary hypertension by recoupling endothelial nitric oxide synthase. Am J Physiol Lung Cell Mol Physiol. 2011; 301(3):L334-45.

16. Du JH, An JZ, Wei N, Guan TJ, Pritchard KA, Shi Y. Increased resistance to LPS-induced myocardial dysfunction in the Brown Norway rats vs. Dahl S rats: roles of inflammatory cytokines and NFκB pathway. Shock. 2010; 33(3):332-6.

15. Amour J, Brzezinska AK, Jager Z, Sullivan C, Weihrauch D, Du J, Vladic N, Shi Y, Warltier DC, Pratt PF Jr, Kersten JR. Hyperglycemia adversely modulates endothelial nitric oxide synthase during anesthetic preconditioning through tetrahydrobiopterin- and heat shock protein 90­mediated mechanisms. Anesthesiology. 2010; 112(3):576-85.

14. Du J, Wei N , Xu H Vasquez-Vivar J, Guan T, Oldham KT, Prichard KA, Shi Y. Identification and functional characterization of phosphorylation sites on GTP cyclohydrolase I. Arterioscler Thromb Vasc Biol. 2009; 29(12):2161-8.

13. An J, Du J, Wei N, Xu H, Pritchard KA, Shi Y. Role of tetrahydrobiopterin in resistance to myocardial ischemia in the Brown Norway vs. Dahl S rat. Am J Physiol Heart Circ Physiol. 2009; 297(5):H1783-91 28.

12. Du J*, Wei N, Guan T Pritchard KA, Shi Y*. Inhibition of CDKS by roscovitine suppressed LPS-induced *NO production through inhibiting NFkappaB activation and BH4 biosynthesis in macrophages. Am. J. Physiol. Cell Physiol. 2009; 297(3): C742-9. *Co-Corresponding author.

11. Du J, Xu H, Wei N, Wakim B, Halligan B, Pritchard KA Jr, Shi Y. Identification of proteins interacting with GTP cyclohydrolase I. Biochem Biophys Res Commun. 2009; 385(2): 143-7.

10. Chen C, Du J, Feng W, Song Y, Lu Z, Xu M, Li Z, Zhang Y. β-adrenergic receptors stimulate interleukin-6 production through Epac-dependent activation of PKCδ/p38 MAPK signaling in neonatal mouse cardiac fibroblasts. Br J Pharmacol. 2012; 166(2):676-88.

9. Du J, Guan T, Zhang H, Xia Y, Liu F, Zhang Y. Inhibitory crosstalk between ERK and AMPK in the growth and proliferation of cardiac fibroblasts. Biochem Biophys Res Commun. 2008; 368(2):402-7.

8. Gong K, Li Z, Xu M, Du J, Lv Z, Zhang Y. A novel protein kinase A-independent, betaarrestin­1-dependent signaling pathway for p38 mitogen-activated protein kinase activation by beta2­adrenergic receptors. J Biol Chem. 2008; 283(43):29028-36.

7. Guan TJ, Qin FJ, Du J, Geng L, Zhang YY, Li M. AICAR inhibits proliferation and induced S-phase arrest, and promotes apoptosis in CaSki cells. Acta Pharmacol Sin. 2007; 28(12): 1984-90.

6. Gong KZ, Zhang H, Du J, Zhang YY. Crosstalk between signaling pathways of adrenoreceptors and signal transducers and activators of transcription 3 (STAT3) in heart. Acta Pharmacol Sin. 2007; 28(2):153-65.

5. Quan Y, Du J, Wang X. High glucose stimulates GRO secretion from rat microglia ROS, PKC, and NF-kappaB pathways. J Neurosci Res. 2007; 85(14):3150-9.

4. Du J, Guan TJ, Zhang H, Xiao H, Han QD, Zhang YY. Phenylarsine oxide inhibited beta­adrenergic receptor-mediated IL-6 secretion: inhibition of cAMP accumulation and CREB activation in cardiac fibroblasts. Biochem Biophys Res Commun. 2007; 352(3):744.

3. Yin F*, Wang YY*, Du J*, Li C, Lu ZZ, Han C, Zhang YY. Noncanonical cAMP pathway and p38 MAPK mediate beta2 -Adrenergic receptor-induced IL-6 production in neonatal mouse cardiac fibroblasts. J Mol Cell Cardiol. 2006; 40(3):384-93. * Co-first author.

2. Du J, Xu N, Song Y, Xu M, Lu ZZ, Han C, Zhang YY. AICAR stimulates IL-6 production via p38 MAPK in cardiac fibroblasts in adult mice: a possible role for AMPK. Biochem Bioph Res Co. 2005; 337(4): 1139-1144. [Link] 

1.  Du J, Liao W, Wang Y, Han C, Zhang Y. Inhibitory effect of 14-3-3 proteins on serum induced proliferation of cardiac fibroblasts. Eur J Cell Biol. 2005; 84:843-85.

Opthalmology

Research Interests

Metabolic signaling in healthy and diseased retina, metabolomics, patient-derived stem cells.

Description of Research

Metabolic network in the visual system
The eye consumes extremely high energy every second and the disturbance of its metabolism can cause blindness. Understanding its unique metabolism is fundamental for retinal degenerative diseases like inherited degeneration, age related macular degeneration (AMD) and diabetic retinopathy.

We are addressing several questions:

• How are nutrients transported and utilized in retinal cells?
• How do photoreceptor cells,glial cells and retinal pigment epithelium coordinate together to make metabolic circuits to maintain their specialized functions?
• How important are glycolysis, mitochondrial oxidative phosphorylation and reductive carboxylation in the retina?

We are using targeted metabolomics. metabolic flux analysis and cell-specific conditional knockout mice animals to test our models.

Targeting metabolism to fight blindness
Our goal is to reveal the metabolic basis for retinal degenerative diseases and to develop new approaches to slow down or prevent blindness. We are using human primary cultured cells, patient-derived retinal cells by iPS technology, genetically modified mouse.models and collaborating with clinicians to test our hypotheses with both targeted and untargeted metabolomics, biomechanical assays and live imaging. We will develop both CRISPR and small molecule-based approaches to attack the metabolic reprogramming in retinal disease