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Goldis Malek

Assistant Professor of Ophthamology
Clinical Sciences
(919) 684 0820
Research Interest: 
Signal transduction
Research Summary: 
Molecular mechanisms and signaling pathways underlying retinal diseases including age-related macular degeneration and diabetic retinopathy.
Research Description: 

Retinal diseases such as age-related macular degeneration (AMD) and diabetic retinopathy result in significant compromise to vision and are devastating to patients. We are interested in identifying molecular mechanisms and potential therapeutic targets in the pathogenesis of these diseases. To address this we have been focusing on the following studies and disease regulating pathways:

(1) Investigating nuclear receptor biology in the human retina and retinal pigment epithelium (RPE) as a function of aging and disease.
Nuclear receptors represent one of the largest families of transcription factors, with 48 present in the human genome. They are critical modulators of developmental and physiological processes and are both targets of drugs as well as chemicals of environmental significance. Many of the processes regulated by nuclear receptors are also associated with retinal diseases such as AMD and diabetic retinopathy. We recently created a nuclear receptor atlas of RPE cells, highlighting the expression of all the nuclear receptors, providing a scaffold to study individual receptors in aging and disease.
(2) Understanding the cellular and molecular pathogenic mechanisms of lipids and oxidants in AMD.
AMD is the most important cause of blindness and visual impairment among the elderly. Epidemiological and animal model studies have shown an association between systemic health factors such as dietary lipids and cigarette smoking to disease progression. We are investigating how lipid-mediated injury of RPE cells promotes pathogenic changes through activation of a subset of nuclear receptors including peroxisome proliferator activated receptors, Liver-X-receptor and the toxin (oxidant) activated aryl hydrocarbon receptor.
(3) Investigating the role of microglial/monocytes and mechanisms by which these cells contribute to retinal degeneration in AMD.
Retinal microglia, effector cells of immunity, are recruited to- and accumulate in the subretinal space and neovascular lesions in AMD. Recruitment of these cells is concomitant with morphological and functional damage of the retina. We are interested in factors involved in recruitment and retention of these cells. Our most recent studies have focused on osteopontin and its receptors, identified in several degenerative diseases of aging as functioning to direct in situ localization of macrophages.

Aryl hydrocarbon receptor deficiency causes dysregulated cellular matrix metabolism and age-related macular degeneration-like pathology.
Hu P, Herrmann R, Bednar A, Saloupis P, Dwyer MA, Yang P, Qi X, Thomas RS, Jaffe GJ, Boulton ME, McDonnell DP, Malek G.
Proc Natl Acad Sci U S A. 2013. 110:E4069-78.

Research resource: nuclear receptor atlas of human retinal pigment epithelial cells: potential relevance to age-related macular degeneration.
Dwyer MA, Kazmin D, Hu P, McDonnell DP, Malek G.
Mol Endocrinol. 2011. 25:360-72.

Reticular pseudodrusen are subretinal drusenoid deposits.
Zweifel SA, Spaide RF, Curcio CA, Malek G, Imamura Y.
Ophthalmology. 2010. 117:303-12.e1.

Molecular genetics of AMD and current animal models.
Edwards AO, Malek G.
Angiogenesis. 2007. 10:119-32.

Apolipoprotein E allele-dependent pathogenesis: a model for age-related retinal degeneration.
Malek G, Johnson LV, Mace BE, Saloupis P, Schmechel DE, Rickman DW, Toth CA, Sullivan PM, Bowes Rickman C.
Proc Natl Acad Sci U S A. 2005. 102:11900-5.