Thomas A. Ferguson, Ph.D.

Professor
Ophthalmology and Visual Sciences
Pathology and Immunology

Immunology Program
Molecular Cell Biology Program
Molecular Microbiology and Microbial Pathogenesis Program

  • 314-362-3745

  • 314-747-5550

  • 314-747-4238

  • 8096

  • 1207A McMillan Building

  • ferguson@vision.wustl.edu

  • https://ophthalmology.wustl.edu/items/ferguson-lab/

  • angiogenesis, apoptosis, autophagy, immunology, lymphocyte, tolerance, photoreceptors, vision,

  • We are examining the role of the autophagy pathway in the function of the retina and its role in diseases of the eye

Research Abstract:

The laboratory studies the role of autophagy in the pathogenesis of eye diseases such as age-related macular degeneration (AMD), retinitis pigmentosa (RP), and other retinal degenerative diseases. We are pursuing this by creating mice in which basal autophagy is deleted in specific cell types in the eye. Recently we found that a link between the autophagy machinery, phagocytosis of photoreceptor outer segments, and the regeneration of chromophore by the visual cycle in the retinal pigment epithelium (RPE). Our results showed that the autophagy protein LC3 associates with single membrane phagosomes containing engulfed POS in an Atg5-dependent manner that also requires Beclin1 but not Ulk1, Atg13, or Fip200 of the autophagy pre-initiation complex. This process termed LC3 associated phagocytosis (LAP) is necessary for optimal vision. Thus, in contrast to conventional autophagy, our studies suggest that a non-canonical form of autophagy functions to support chromophore regeneration through the efficient processing of outer segments by the RPE.
Our studies have also shown that autophagy is critical to function and long term survival of rod and cone photoreceptors. Studying autophagy in photoreceptors has given us new insights into the metabolism, function, and stress responses of these cells that are critical to vision. Cones are particularly dependent on autophagy as they utilize this process for their continued function in intense bright light and activate the pathway in response to light stress and systemic nutrient starvation. We are currently examining the importance of autophagy to the Muller glia cells of the retina.

Selected Publications:

Yao J, Qiu Y, Frontera E, Jia L, Khan NW, Klionsky DJ, Ferguson TA, Thompson DA, Zacks DN. Inhibiting autophagy reduces retinal degeneration caused by protein misfolding. Autophagy. 2018 Jul 13:1-13. PMID: 29940785
Muniz-Feliciano L, Doggett TA, Zhou Z, Ferguson TA. RUBCN/rubicon and EGFR regulate lysosomal degradative processes in the retinal pigment epithelium (RPE) of the eye. Autophagy 13:2072-2085, 2017 PMCID: PMC5788552
Zhou Z, Doggett TA, Sene A, Apte RS, Ferguson TA. (2015). Autophagy supports survival and phototransduction protein levels in rod photoreceptors. Cell Death Differ. 22:488-98. PMCID: PMC4326583
LeBlanc PM, Doggett TA, Choi J, Hancock MA, Durocher Y, Frank F, Nagar B, Ferguson TA*, Saleh M*. (2014). An immunogenic peptide in the A box of HMGB1 reverses apoptosis-induced tolerance through RAGE. J Biol Chem. 289:7777-7786. *co-senior authors. PMC3953289. Named “Best of JBC” for 2014
Kim JY, Zhao H, Martinez J, Doggett TA, Kolesnikov AV, Tang PH, Ablonczy Z, Chan CC, Zhou Z, Green DR, Ferguson TA. (2013). Noncanonical autophagy promotes the visual cycle. Cell 154:365-376. PMC3744125
Complete Bibliography: https://www.ncbi.nlm.nih.gov/sites/myncbi/thomas.ferguson.1/bibliography/40090195/public/?sort=date&direction=descending

Last Updated: 8/14/2018 2:12:10 PM

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