Ophthalmology; Biochemistry; Blanchette Rockefeller Neurosciences Institute
PhD in Pathophysiology, Peking University, Beijing, China
Postdoctoral Fellow, Pediatrics Surgery, Medical College of Wisconsin
Senior Fellow, Biochemistry, University of Washington
Retina has extremely active energy metabolism to support its function in processing light signals into electrical signals. Differs from the brain, retina has unique laminated structure (Figure 1, below) and relies much more on aerobic glycolysis (Figure 2, below). Mutations in the metabolism genes such as PDE6, IDH3, HK, IMPDH, and NMNAT1 exclusively affect retina to cause vision loss in inherited retinal degeneration in humans. Retina has at least six different cell types and they are highly interactive and inter-dependent in nutrient utilization (Figure 2, below). The malfunction of metabolism in RPE cells and Müller glial cells could lead to photoreceptor degeneration in age-related macular degeneration and Macular telangiectasia type 2. Targeting metabolism might be a promising approach to treat retinal degenerative diseases.
Our lab integrates multidisciplinary approaches including mass spectrometry, stable isotope tracers, gene editing, animal models and stem cell technology to study the roles of metabolic regulation and dys-regulation in the heathy and diseased retinas.
Retina has a unique structure with different cell types in layers (Figure 1). Model for metabolic pathways in the mouse retina (Figure 2). ( J Neurosci Res. 2015; 93(7): 1079–1092 .)
- Human RPE metabolism and metabolite transport (NIH RO1, 2016-2020)
- NAD metabolism in normal and disease-specific human RPE cells (Brightfocus Foundation, 2016-2018)
- Mitochondrial pyruvate carrier in the retina
- NAD metabolism in inherited retinal degeneration
- Metabolomics and metabolic flux analysis --- (using GC MS, LC QQQ and LC Q exactive to quantify central carbon metabolites and metabolic reactions)
- Tissue culture --- (Retinal explant, RPE cell culture and stem cell diffrentiation)
- In vitro Enzyme assay --- (UV, Fluorescence and Luminescence microplate reader)
Allison B. Grenell, BS
- Chao JR, Knight K, Engel AL, Jankowski C, Wang Y, Manson MA, Gu H, Djukovic D, Raftery D, Hurley JB, Du J. (2017) Human retinal pigment epithelial cells prefer proline as a nutrient and transport metabolic intermediates to the retinal side. J Biol Chem, 292(31): 12895-12905. PMCID: PMC5546030 [available on 2018-08-04]
- Du J, Yanagida A, Knight K, Engel AL, Vo AH, Jankowski C, Sadilek M, Tran VT, Manson MA, Ramakrishnan A, Hurley JB, CHao JR. (2016) Reductive carboxylation is a major metabolic pathway in the retinal pigment epithelium. Proc Natl Acad Sci USA, 113(51): 14710-15. PMCID: PMC5187684
- Gu H, Carroll PA, Du J, Zhu J, Neto FC, Eisenman RN, Raftery D. (2016) Quantitative method to investigate the balance between metabolism and proteome biomass: Starting from glycine. Angew Chem Int Ed Engl, 55(50): 15646-50.
- Zhang L, Du J, Justus S, Hsu CW, Bonet-Ponce L, Wu WH, Tsai YT, Wu WP, Jia Y, Duong JK, Mahajan VB, Lin CS, Wang S, Hurley JB, Tsang SH. (2016) Reprogramming metabolism by targeting sirtuin 6 attenuates retinal degeneration. J Clin Invest, 126(12): 4659-73. PMCID: PMC5127684
- Contreras L, Ramirez L, Du J, Hurley JB, Satrústegui J, de la Villa P. (2016) Deficient glucose and glutamine metabolism in Aralar/AGC1/Slc25a12 knockout mice contributes to altered visual function. Mol Vis, 22: 1198-1212. PMCID: PMC5063090
- 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.
- 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.
- Du J, Linton JD, Hurley JB. Probing metabolism in the intact retina using stable isotope tracers. Methods in Enzymology. 2015; 561:149-70.
- 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.
- 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
- 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.