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 (Left panel below) and relies much more on aerobic glycolysis (Right panel 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 (Right panel 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.
- 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
- Proline metabolism in the RPE
- Metabolomics and metabolic flux analysis ---(using GC MS, LC QQQ and LC Q exactive to quantify central carbon metabolites and metabolic reactions)
- Tissue culture and Stem Cell---(Retinal explant, RPE cell culture and stem cell diffrentiation)
- In vitro Enzyme assay---(UV, Fluorescence and Luminescence microplate reader)
- Molecular biology--(CRISPR, molecular cloning, PCR, Western blot)
- Imaging-- (Fluorescent microscope, Con-focal microscope, Immunofluorescence and in vivo imaging with genetically modified sensors)
- Animal models-- (Whole body Knockout, Conditional Knockout, transgenic, electroretinogram, Optical coherence tomography
- Dr. Jennifer Chao University of Washington
- Dr. James Hurley University of Washington
- Dr. Stephen Tsang Columbia University
- Dr. Douglas Vollrath Stanford University
- Dr. Jason Miller University of Michigan
- Dr. Deborah Ferrington University of Minnesota
- Dr. Terry Gullion WVU Chemistry
- Dr. Nancy Philp Thomas Jefferson University