Research

Feature of an undergraduate researcher: Rachel Mcneel

A snapshot of Du Lab

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.

Retina has a unique structure with different cell types in layers (Left).  Model for metabolic pathways in the mouse retina (right).  (J Neurosci Res. 2015; 93(7): 1079–1092.)

Current Projects

  1. Mitochondrial Pyruvate transport in retinal health and disease                (NIH R01 EY031324, 2021-2025)
  2. Proline metabolism in eye health and disease                                         (NIH R01 EY032462, 2021-2026)
  3. Human RPE metabolism and metabolite transport                                  (NIH R01 EY026030, 2022-2027, Co-PI with Dr. Jennifer Chao from University of Washington)
  4. Metabolism of AMD iPSC-derived RPE                                                       (NIH U01 EY034591, 2022-2025, Co-PI with Dr. Jennifer Chao from University of Washington)
  5. Mitochondrial defects in AMD RPE with genetic risk factors                 (NIHR01 EY028554, 2022-2026, Co-I from Dr. Deborah Ferrington from UCLA)
  6. Targeting proline metabolism in AMD                                                       (Brightfocus Foundation, 2020-2022)
  7. Nutritional strategies in age-related macular degeneration                      (Retinal Research Foundation, 2019-2022)

Research Method

  1. Metabolomics and metabolic flux analysis ---(using GC MS, LC QQQ and LC Q exactive to quantify central carbon metabolites and metabolic reactions)
  2. Tissue culture and Stem Cell---(Retinal explant, RPE cell culture and stem cell diffrentiation)
  3. In vitro Enzyme assay---(UV, Fluorescence and Luminescence microplate reader)
  4. Molecular biology--(CRISPR, molecular cloning, PCR, Western blot)
  5. Imaging-- (Fluorescent microscope, Con-focal microscope, Immunofluorescence and in vivo imaging with genetically modified sensors)
  6. Animal models-- (Whole body Knockout, Conditional Knockout, transgenic, electroretinogram, Optical coherence tomography

Collaborators

 

  1.  Jennifer Chao                                University of Washington           
  2.  Deborah Ferrington                      UCLA
  3. John Ash                                         Florida University
  4. Bryan Jones                                   University of Utah
  5. Nancy Philp                                    Thomas Jefferson University
  6. Douglas Dean                                 University of Louisville
  7. Eric Pierce                                       Harvard University
  8. Douglas Vollrath                             Stanford University
  9. Mark Gilles                                      University of Sydney, Australia
  10. Muayyad Al-Ubaidi                         University of Houston
  11. Eric Kelly                                         WVU
  12. Saravanan Kolandaivelu                WVU
  13. Susan Brockerhoff                         University of Washington
  14. James Simpkins                             WVU
  15. Roberta Leonardi                            WVU
  16. James Hurley                                    University of Washington
  17. Shinghua Ding                                  University of Missouri