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Human Molecular Genetics

Prof. Peter Humphries

  • Genetic etiologies of degenerative diseases of the human retina.
  • Development of gene therapy for such conditions.

The Research Interests of Pete Humphries are largely in the area of visual neuroscience:

Prof Pete Humphries

Globally, over 160 million people are estimated to be visually impaired, in spite of the fact that up to 70% of global visual handicap, caused by cataract, glaucoma, corneal opacities and infection, is treatable or preventable (including most open-angle glaucomas). In the developed World, conditions that are essentially eclipsed by the vastly more common forms of world blindness become very much more visible. These are the hereditary retinopathies (prominent among which is Retinitis Pigmentosa), Age-related Macular Degeneration (AMD) and Proliferative Diabetic Retinopathy (PDR). Also, possibly up to 10% of cases of Open-angle Glaucoma either do not respond adequately, or become resistant to conventional pressure-reducing medications. For three decades, Pete's research has been directed toward understanding the molecular pathologies associated with retinal degeneration, early studies focusing almost exclusively on hereditary retinopathies, for example, in the localization of genes for RP to chromosomes 3q (rhodopsin), 6p (RDS-peripherin) and 7q (inosine monophosphate dehydrogenase 1) and on the generation of targeted murine disease models. As a result of world efforts, it is now clear that hereditary retinopathies possibly represent the most genetically heterogeneous of any group of hereditary conditions for which molecular pathologies have been explored. On one hand, the progressive unfolding of an immensely complex genetic landscape has been inspirational, but on the other, and in a very much more translational sense, this same genetic heterogeneity presents an immensely significant challenge - developing gene medicines for what could be several hundred individually rather rare hereditary conditions is a major logistical and economic hurdle that must now be surmounted. In this regard, a major recent focus of research has been in the development of procedures for modulating permeability at the blood-brain and inner blood retina barriers such as to allow access to the brain and retina of systemically administered low molecular weight potentially protective compounds targeting molecular pathologies common to multiple forms of disease (protein misfolding or aggregation, oxidative stress, neuroprotection, etc) which could be used either singly or in a combinatorial sense together with gene therapies. More recently, multifactorial conditions, including AMD and glaucoma have become a major focus of research.

Peter's work on the development of novel aspects of glaucoma therapy is supported by an advanced grant from the European Research Council.


McWilliam P, Farrar GJ, Kenna, P, Bradley DG, Humphries MM, Sharp EM, McConnell DJ, Lawler M, Sheils D, Stephens K, Daiger SP and Humphries P. Autosomal dominant retinitis pigmentosa: localization of an adRP gene to the long arm of chromosome 3. Genomics, 5, 612-619, 1989.

Farrar GJ, Kenna P, Jordan S, Kumar-Singh R, Humphries MM, Sharp EM, Sheils D and Humphries P. A 3 base-pair deletion in the peripherin gene in one form of retinitis pigmentosa. Nature, 354, 478-480, 1991.

Humphries P, Kenna P and Farrar GJ. On the molecular genetics of retinitis pigmentosa. Science, 256, 804-808, 1992.

Jordan SA, Farrar GJ, Kenna P, Humphries MM, Sheils D, Kumar-Singh R, Sharp EM, Soriano N, Ayuso C, Benitez J and Humphries P. Localisation of an autosomal dominant retinitis pigmentosa gene to chromosome 7q. Nature Genetics, 4, 54-57, 1993.

Humphries P, Kenna P and Farrar GJ. New dimensions in Macular Dystrophies. Nature Genetics, 8, 315-317, 1994.

Humphries MM, Rancourt D, Farrar GJ, Kenna P, Hazel M, Bush RA, Sieving PA, Sheils DM, McNally N, Creighton P, Erven A, Boros A, Gulya K, Capecchi MR and Humphries P. Retinopathy induced in mice by targeted disruption of the rhodopsin gene. Nature Genetics, 15, 216-219, 1997.

Campbell M, Nguyen AT, Kiang AS, Tam LC, Gobbo OL, Kerskens C, Ni Dhubhghaill S, Humphries MM, Farrar GJ, Kenna PF, Humphries P. An experimental platform for systemic drug delivery to the retina. Proc Natl Acad Sci USA. 2009, 106(42):17817-22.

Campbell M, Humphries MM, Nguyen ATH, Gobbo OL, Tam LCS, Suzuki M, Hanrahan F, Ozaki E, Farrar G-J, Kiang A-S, Kenna PF, Humphries P. Systemic low molecular weight drug delivery to preselected neuronal regions. EMBO Mol Med, 3, 235-245, 2011.

Doyle SL*, Campbell M*, Ozaki E, Salomon RG, Mori A, Kenna PF, Kiang A-S, Humphries MM, Lavelle E, O'Neill L, Hollyfield JG, Humphries P. NLRP3 plays a protective role during the development of age related macular degeneration through the induction of IL-18 by drusen components. Nature Medicine, 18(5), 791-8, 2012
*joint 1st Authors.

Campbell M, Hanrahan F, Gobbo OL, Kelly ME, Kiang AS, Humphries MM, Nguyen AT, Ozaki E, Keaney J, Blau CW, Kerskens CM, Cahalan SD, Callanan JJ, Wallace E, Grant GA, Doherty CP, Humphries, P. Targeted suppression of claudin-5 decreases cerebral edema and improves cognitive outcome following traumatic brain injury. Nature Communications 2012 May 22;3:849. doi: 10.1038/ncomms1852.

Doyle SL, Ozaki E, Brennan K, Humphries MM, Mulfaul K, Keaney J, Kenna PF, Maminishkis A, Kiang AS, Saunders SP, Hams E, Lavelle EC, Gardiner C, Fallon PG, Adamson P, Humphries P, Campbell M. IL-18 attenuates experimental choroidal neovascularization as a potential therapy for wet age-related macular degeneration. Science Translational Medicine 2014 Apr 2;6(230):230ra44. doi: 10.1126/scitranslmed.3007616.

Keaney J, Walsh DM, O'Malley T, Hudson N, Crosbie DE, Loftus T, Sheehan F, McDaid J, Humphries MM, Callanan JJ, Brett MM, Humphries P and Campbell M. Autoregulated paracellular clearance of Amyloid-β across the blood-brain barrier. Science Advances 2015 Sci Adv. 2015 Sep 4;1(8):e1500472.