Welcome to !

Dr Nick Di Girolamo
Ocular Diseases Research Unit, Centre for Infection and Inflammation,
University of New South Wales
Sydney, NSW 2052
Email: n.digirolamo@unsw.edu.au
Tel: +61-2-9385-2538
Fax: +61-2-9385-1389

Our research focuses on the involvement of matrix metalloproteinases (MMPs) and their tissue inhibitors the TIMPs in the pathogenesis of ultraviolet radiation (UVR)-induced human ocular surface diseases which range in severity from benign to malignant neoplastic lesions. We have investigated the intracellular signaling pathways activated following UV-exposure that result in the production of pro-inflammatory and angiogenic cytokines that impact the expression of MMPs in such lesions. These studies have been performed on resected tissue specimens and in cultured cells for which we have established appropriate models that simulate physiological solar UVR exposures in a controlled laboratory setting. Using such culture models we have identified several immunomodulatory agents that affect the expression of cytokines and MMPs and plan to develop these further as topical therapeutic agents to avoid traumatic surgical excisions.

The second arm of our study focuses on MMP gene promoter single nucleotide polymorphisms (SNP) and their association with the risk of developing solid epithelial cancers such as colorectal, breast and prostate cancer. Recently, we generated data that challenges the current dogma in this field where we identified a significant survival advantage in patients with colorectal cancer harbouring the MMP-1 -1607 gene promoter polymorphism (Br J Cancer 2007), a functional polymorphism which is associated with enhanced MMP-1 expression. To further elucidate the mechanism behind this observation, we generated stable transfectant clones of colorectal cancer cells that have had their normally over-expressed MMP-1 gene silenced and plan to transplant these cells orthotopically into nude mice for tracking studies and to determine tumour load, angiogenesis, metastatic activity and survival.

More recently we have embarked on studies that will allow us to address whether MMPs may be utilized by adult and fetal stem cells as a means of assisting their migration from their niche microenvironment into regions of tissue regeneration. To help us elucidating this role we have developed a novel assay that measures MMP secretions in real time from cultured cells (Nano Lett 2009).
Professor Carolyn Geczy
Professor Roland Stocker
Professor Gary Halliday
Professor Jane Provis
Dr Michele Madigan
Di Girolamo N, Coroneo MT, Wakefield D. Epidermal growth factor receptor signaling is partially responsible for the increased matrix metalloproteinase-1 expression in ocular epithelial cells after UVB radiation. Am J Pathol. 2005;167:489-503.

Di Girolamo N, Endoh I, Jackson N, Wakefield D, McNeil P, Yan W-X, Geczy C, Arm JP, Tedla N. Human mast cell-derived gelatinase B (MMP-9) is regulated by inflammatory cytokines: role in cell migration. J Immunol. 2006;177:2638-2650.

Zhang G, Fahmy RG, Di Girolamo N, Khachigian LM. JUN siRNA regulates matrix metalloproteinase-2 expression, microvascular endothelial growth and retinal neovascularization. J Cell Sci. 2006;119:3219-3226.

Lai K, Di Girolamo N, Jager M, Conway RM, Madigan MC. The effect of ultraviolet radiation on choroidal melanocytes and melanoma cell lines: cell survival and matrix metalloproteinase production. Graefes Arch Clin Exp Ophthalmol. 2007;245:715-724.

Hettiaratchi A, Hawkins NJ, Ward RL, Hunt JE, Wakefield D, Di Girolamo N. The collagenase (MMP-1) gene promoter polymorphism -1607/2G is associated with favorable prognosis in patients with colorectal cancer. Br J Cancer. 2007;96:783-792.

Wu BJ, Di Girolamo N, Beck K, Hanratty CG, Choy K, Hou JY, Ward MR, Stocker R. Probucol retards compensatory arterial remodeling in apolipoprotein E deficient mice by decreasing macrophage and matrix metalloproteinase-9 and -2. J Pharmacol Exp Therap. 2007;321:477-484.

Ng J, Coroneo MT, Wakefield D, Di Girolamo N. Ultraviolet radiation and the role of matrix metalloproteinases in the pathogenesis of ocular surface squamous neoplasia. Invest Ophthalmol Vis Sci. 2008;49:5259-5306.

McCluskey PJ, Wakefield D, Molteno A, Di Girolamo N. Otago glaucoma surgery outcome study: The pattern of expression of MMPs and TIMPs in bleb capsules surrounding Molteno implants. Invest Ophthalmol Vis Sci. 2009;50:2161-2164.

Kilian KA, Lai LMH, Magenau A, Cartland S, Bocking T, Di Girolamo N, Gal M, Gaus K, Gooding JJ. Smart tissue culture: in situ monitoring of cellular secretion with nanostructured photonic crystals. Nano Lett. 2009;9:2021-2025.

Questions/suggestions? Please contact the Network Administrator.
Copyright © by International Protease Network All Right Reserved.