Jianhai Du, PhD

Research Interests

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

Publications

2025

100. Ratliff C, Hansman D, Ngo T, Xiang Y, Puja A, Eminhizer M, Lu J, Mascari I, Alabdallat D, Du J*. Absolute quantification of TCA cycle intermediates in mouse ocular tissues reveals distinct tissue- and sex-specific mitochondrial metabolism. bioRxiv 2025.09.25.678562; doi.org/10.1101/2025.09.25.678562. PMID: 41040287 *Corresponding Author.

99. Puja A, Xu R, Eminhizer M, Ngo T, Zhang Y, Wang Q, Saravanan M, Du J*. Beyond Ornithine Metabolism in Gyrate Atrophy: Tissue-Specific Proteomic Insights into Neonatal and Adult OAT Deficiency. bioRxiv. 2025: 2025.09.10.675383. doi: 10.1101/2025.09.10.675383. PMID: 41000928. *Corresponding Author.

98. Rajala A, Trevino LJ, Saravanan T, Black TM, Bhat AM, Ngo T, Eminhizer M, Du J, Ramamurthy V, Rajala RVS. Loss of PIKfyve in Rod Photoreceptors and RPE Cells Leads to Endolysosomal Dysfunction and Retinal Degeneration. bioRxiv. 2025: 2025.09.15.676371. doi: 10.1101/2025.09.15.676371.PMID: 4100096.

97. Cahill ME, Chmelik K, Brothers BA, Ashcraft ME, Guan T, Puja A, Xiang YX, Shaw LM, Du J, Deng WT. Gene Therapy Rescues Cone Function in an All-cone Retina Mouse Model for Blue Cone Monochromacy with the Most Common C203R Missense Mutation. bioRxiv, 2025.09. 04.674359. doi.org/10.1101/2025.09.04.674359.

96. Zeng Y, Zhang T*, Cornish E, Lee SR, Yam M, Eminhizer M, Zeng J, Zhang J, Zeng S, Wei X, Yang J, Zhu M, Chang A, Zhang M, Du J*, Zhu L, Gillies MC. Dysregulated Proline Metabolism Contributes to Subretinal Fibrosis in Neovascular AMD: Therapeutic Potential of Prolyl-4-Hydroxylase Inhibition. bioRxiv, 2025.04. 13.648057. doi.org/ 10.1101/2025.04.13.648057. PMID: 41031003 *Corresponding Author.

95.Rutter KM, Giarmarco MM, Truong V, Wang Y, Eminhizer M, Xiang Y, Cleghorn WM, Sanchez G, Burrell AL, Kollman JM, Du J, Brockerhoff SE. Retinopathy-associated inosine monophosphate dehydrogenase 1 mutations cause metabolic and filament defects in cones. Dis Model Mech. 2025 Aug 18:dmm.052389. doi: 10.1242/dmm.052389. PMID: 40820815. 

94. Emery D, Vukmanic E, Wang Y, Eminhizer M, Wang F, Lu X, Wang W, Kini A, Chen Y, Fortuny E, James RF, Liu Y*, Du J*, Dean DC*. Metabolic regulation of visual acuity. Sci Adv. 2025 Jun 27;11(26):eadx2050. doi: 10.1126/sciadv.adx2050. . PMID: 40577465. *Corresponding Author.

93. Cal K, Leyva A, Rodríguez-Duarte J, Ruiz S, Santos L, Garat MP, Colella L, Ingold M, Benitez-Rosendo A, Pérez-Torrado V, Vilaseca C, Galliussi G, Ziegler L, Peclat TR, Bresque M, Handy RM, King R, Menezes Dos Reis L, Alves JM, Espasandín C, de la Sovera V, Breining P, Dapueto R, Lopez A, Thompson KL, Lino CA, França JV, Vieira TS, Rattan R, Agorrody G, DeVallance E, Haag J, Meadows E, Lewis SE, Santana Barbosa GC, Lai de Souza LO, Chichierchio MS, Valez V, Aicardo A, Contreras P, Vendelbo MH, Jakobsen S, Kamaid A, Porcal W, Calliari A, Verdes JM, Du J, Wang Y, Hollander JM, White TA, Radi R, Moyna G, Quijano C, O’Doherty R, Moraes-Vieira P, Giri S, Holloway GP, Festuccia WT, Leiria LO, Leonardi R, Mori MA, Camacho-Pereira J, Kelley EE, Duran R, López GV, Chini EN, Batthyány C, Escande C. A nitroalkene derivative of salicylate, SANA, induces creatine-dependent thermogenesis and promotes weight loss. Nat Metab. 2025 Jun 17. doi: 10.1038/s42255-025-01311-z. PMID: 40527924

92. Zhang T, Jin K, Zeng S, Yang P, Zhu M, Zhang J, Chen Y, Lee S, Yam M, Zeng Y, Lu X, Loo L, Neely GG, Chang A, Zhou F, Du J, Fan X, Zhu L, Gillies MC.Divergent redox responses of macular and peripheral Müller Glia: Implications for retinal vulnerability. Redox Biol. 2025 May 24;85:103691. doi: 10.1016/j.redox.2025.103691. PMID: 4049926

91. Ratnapriya R, Grassman F, Chen R, Hewitt A, Du J, Saban DR, Klaver CCW, Ash J, Stambolian D, Tumminia SJ, Qian J, Husain D, Iyengar SK, den Hollander AI. Functional genomics in age-related macular degeneration: From genetic associations to understanding disease mechanisms. Exp Eye Res. 2025 Mar 13:110344.  Online ahead of print. PMID: 40089136 

90. Caruso SM, Cui X, Robbings BM, Heaps N, Demikrol A, Lopes da Costa B, Hass DT, Quinn PM, Du J, Hurley JB, Tsang SH.Ablating VHL in Rod Photoreceptors Modulates RPE Glycolysis and Improves Preclinical Model of Retinitis Pigmentosa. J Clin Invest. 2025 Feb 11:e185796.  PMID: 39932789

89. Puja A, Lu J, Du J. Ocular Tissue-Specific Amino Acid Metabolism in Gyrate Atrophy. Adv Exp Med Biol. 2025;1468:279-284.  PMID: 39930209.

88. Hansman DS, Du J, Casson RJ, Peet DJ. Eye on the horizon: The metabolic landscape of the RPE in aging and disease. Prog Retin Eye Res. 2025 Jan;104:101306. PMID: 39433211

2024

87. Shang P, Ambrosino H, Hoang J, Geng Z, Zhu X, Shen S, Eminhizer M, Hong E, Zhang M, Qu J, Du J, Montezuma SR, Dutton JR, Ferrington DA. The Complement Factor H (Y402H) risk polymorphism for age-related macular degeneration affects metabolism and response to oxidative stress in the retinal pigment epithelium. Free Radic Biol Med. 2024 Nov 2:S0891-5849(24)01015-3. doi: 10.1016/j.freeradbiomed.2024.10.307. Online ahead of print. PMID: 3949173.

86.Rizwan S, Toothman B, Li B, Engel AJ, Lim RR, Niernberger S, Lu J, Ratliff C, Xiang Y, Eminhizer M, Chao JR, Du J. Metabolic phenotyping of healthy and diseased human RPE cells. Invest Ophthalmol Vis Sci. 2024 Sep 3;65(11):5. doi: 10.1167/iovs.65.11.5.PMID: 39230994

85. Wang Y, Becker S, Finkelstein S, Dyka FM, Liu H, Eminhizer M, Hao Y, Brush RS, Spencer WJ, Arshavsky VY, Ash JD, Du J, Agbaga MP, Vinberg F, Ellis JM, Lobanova ES. Acyl-CoA synthetase 6 controls rod photoreceptor function and survival by shaping the phospholipid composition of retinal membranes. Commun Biol. 2024 Aug 21;7(1):1027. doi: 10.1038/s42003-024-06691-8. PMID: 39169121 

84. Rajala A, Rajala R, Bhat MA, Eminhizer M, Hao J, Du J, Rajala RVS. Age-related retinal degeneration resulting from the deletion of Shp2 tyrosine phosphatase in photoreceptor neurons.
Cell Death Dis. 2024 Aug 8;15(8):577. doi: 10.1038/s41419-024-06924-y. PMID: 39117618.

83. Chen M, Wang Y, Dalal R, Du J, Vollrath D. Alternative oxidase blunts pseudohypoxia and photoreceptor degeneration due to RPE mitochondrial dysfunction. Proc Natl Acad Sci U S A. 2024 Jun 18;121(25):e2402384121. doi: 10.1073/pnas.2402384121. Epub 2024 Jun 12. PMID: 38865272

82.Grenell A, Singh C,  Raju M,  Wolk A,  Dalvi S, Jang GF,  Crabb JS,  Hershberger CE, Manian K, Crabb JW,  Singh R, Du J,  Anand-Apte B.  Tissue Inhibitor of Metalloproteinase 3 (TIMP3) mutations increase glycolytic activity and dysregulate glutamine metabolism in RPE cells. Mol Metab. 2024 Jul 22;88:101995. doi: 10.1016/j.molmet.2024.101995. Online ahead of print.
PMID: 39047907

81. Nolan ND, Cui X, Robbings BM, Demirkol A, Pandey K, Wu WH, Hu HF, Jenny LA, Lin CS, Hass DT, Du J, Hurley JB, Tsang SH. CRISPR editing of anti-anemia drug target rescues independent preclinical models of retinitis pigmentosa. Cell Rep Med. 2024 Mar 15:101459. doi: 10.1016/j.xcrm.2024.101459. Online ahead of print. PMID: 38518771.

80. Zhang T,  Jin K, Zeng S, Yang P, Zhu M, Zhang J,  Chen Y,  Lee S,  Yam M, Zeng Y,  Lu X,  Loo L,  Neely GG,  Chang A,  Zhou F, Du J, Fan X,  Zhu L,  Gillies MC. Sacrificing Adaptability for Functionality: The Ivory Tower of Macular Müller Cells. bioRxiv [Preprint].  2024 April 30,. doi: https://doi.org/10.1101/2024.04.28.590478. 

2023

79. Zhu S, Xu R, Engel AL, Wang Y, McNeel R, Hurley JB, Chao JR, Du J. Proline provides a nitrogen source in the retinal pigment epithelium to synthesize and export amino acids for the neural retina. J Biol Chem. 2023 Sep 21:105275. doi: 10.1016/j.jbc.2023.105275. Online ahead of print. PMID: 37741457

78. Lee SJ, Emery D, Vukmanic E, Wang Y, Lu X, Wang W, Fortuny E, James R, Kaplan HJ, Liu Y, Du J, Dean DC. Metabolic transcriptomics dictate responses of cone photoreceptors to retinitis pigmentosa. Cell Rep. 2023 Aug 31;42(9):113054. doi: 10.1016/j.celrep.2023.113054. Online ahead of print. PMID: 3765662

77. Xu R, Wang Y, Du J, Salido EM. Retinal Metabolic Profile on IMPG2 Deficiency Mice with Subretinal Lesions. Adv Exp Med Biol. 2023;1415:457-463. doi: 10.1007/978-3-031-27681-1_67.
PMID: 37440072

76. Saravanan M, Xu R, Roby O, Wang Y, Zhu S, Lu A, Du J. Tissue-Specific Sex Difference in Mouse Eye and Brain Metabolome Under Fed and Fasted States. Invest Ophthalmol Vis Sci. 2023 Mar 1;64(3):18. doi: 10.1167/iovs.64.3.18.PMID: 36892534

75. Cui X, Chang YJ, Jenny LA, Levi SR, Du J, Tsang SH. Metabolite Extraction from RPE Cells and Retinas Related to Retinitis Pigmentosa. Methods Mol Biol. 2023;2560:257-265. doi: 10.1007/978-1-0716-2651-1_24. PMID: 36481902

2022

74. Zhu S,  Huang J, Xu R, Wang Y, Wan Y, McNeel R, Parker ED, Kolson D, Yam M, Webb B, Zhao C, Du J. Isocitrate dehydrogenase 3b is required for spermiogenesis but dispensable for retinal degeneration. J Biol Chem. 2022 Sep;298(9):102387. doi: 10.1016/j.jbc.2022.102387. PMID: 35985423

73.  Chen Y, Zhang T, Zeng S, Xu R, Jin K, Coorey NJ, Wang Y, Wang K, Lee SR, Yam M, Zhu M, Chang A, Fan X, Zhang M, Du J, Gillies MC, Zhu L.Transketolase in human Müller cells is critical to resist light stress through the pentose phosphate and NRF2 pathways. Redox Biol. 2022 Jun 24;54:102379. doi: 10.1016/j.redox.2022.102379. PMID: 35779441

72. Daniele LL, Han JYS, Samuels IS, Komirisetty R, Mehta N, McCord JL, Yu M, Wang Y, Boesze-Battaglia K, Bell BA, Du J, Peachey NS, Philp NJ.Glucose uptake by GLUT1 in photoreceptors is essential for outer segment renewal and rod photoreceptor survival. FASEB J. 2022 Aug;36(8):e22428. doi: 10.1096/fj.202200369R. PMID: 35766190

71. 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. 2022 Jan;298(1):101441. PMID: 34813793.

70. Engel AL, Wang Y, Khuu TH, Worrall E, Manson MA, Lim RR, 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. Exp Eye Res. 2022 Feb; 215:108899. doi: 10.1016/j.exer.2021.108899. PMID: 34929159.

2021

69. 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

68. 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

67.  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. 

66. 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.

65. 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.

64. Xu R, Wang Y and Du J. Tracing Nitrogen Metabolism in Mouse Tissues with Gas Chromatography-Mass Spectrometry . Bio Protoc. 2021 Feb 20;11(4):e3925.  PMID: 33732812. 

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