Welcome to the John Laboratory!

Our research investigates the molecular features of complex diseases that lead to the death of neural cells (neurodegenerations). Most of our projects focus on glaucoma. Glaucoma is a major cause of human blindness and is often associated with elevated pressure within the eye itself (intraocular pressure, or IOP). The harmfully high pressure damages retinal ganglion cells (RGCs) resulting in a pressure-induced neurodegeneration. We use mouse models to study glaucoma. We combine genetics with genomics, cell/molecular biology and physiology to understand glaucoma. We are identifying new genes and pathways that cause glaucoma. We study how abnormal ocular development and other processes lead to high IOP and glaucoma. We are also determining how high intraocular pressure damages retinal neurons.

Breakthroughs include:

  1. We have causally implicated pigmentary pathways and the immune system in a pigmentary form of glaucoma. This suggests that anti-inflammatory treatments may be beneficial for alleviating this disease.
  2. We have identified a pathway involving the molecule L-DOPA that is important for normal ocular development, and shown that L-DOPA administration can alleviate disease phenotypes in a mouse model that has a mutation in a human glaucoma gene.
  3. We discovered that a mutant collagen molecule causes glaucoma-related phenotypes and stroke in mice. Similar mutations exist in human patients. The mutations weaken blood vessels and predispose to trauma-induced hemorrhage, suggesting that behavioral modifications to avoid trauma will be beneficial to patients.
  4. We discovered that the molecule BAX is essential for RGC death in an inherited glaucoma.  Additionally, we demonstrated that distinct pathways participate in the degeneration of the cell body and axon (structure that connects the cell to the brain) of the same RGC. These studies are providing new insights into disease mechanisms and are suggesting new targets for pharmacological treatment.
  5. We recently discovered a radiation treatment that completely prevents glaucomatous neurodegeneration in the vast majority of treated animals. Experiments to understand how this protection occurs are underway, with the aim of devising new treatments for human glaucoma and possibly other neurodegenerative diseases.

Our research interests are available through: http://research.jax.org/faculty/john/research.html