Lens Research Laboratory

Lab head: Associate Professor Frank Lovicu
Location: Anderson Stuart Building, Camperdown Campus & Save Sight Institute, Macquarie Street, Sydney CBD.

The work of the Lens Research Laboratory is primarily directed at identifying the molecules and mechanisms that govern the behaviour of cells of the ocular lens, in health, ageing and disease.

Studies conducted by this laboratory have identified a number of molecules that play key roles in both normal and pathological lens development and growth. Currently this laboratory is working to gain a better understanding of how these molecules are regulated in the eye. This is fundamental to identifying new therapeutics for retarding or preventing cataract and blindness, one of the most common and costly diseases of ageing.

Lab members: A/Prof F. J. Lovicu (Head) Prof. J W. McAvoy (Head), Dr. Yuki Sugiyama (Postdoctoral Fellow) Dr. Lucy Dawes (Postdoctoral Fellow) Ms Li Wen (Research Assistant) Ms Jessica Boros (Research Assistant) Ms Hailey Shin (PhD student) Ms Seonah Jee (Graduate Diploma Student)
Funding: NHMRC (Australia), NEI (NIH, USA)
Research approach equipment: Using a range of techniques (including tissue culture, immunohistochemistry, in situ hybridisation, PCR, chromatography, Western blotting, light and electron microscopy, in vitro biological assays and transgenic mouse strategies), we investigate the expression, effects and function of different growth factors and their receptors as well as the regulation of their intracellular signalling, both in normal lens development and pathology.
Publications:

Lovicu FJ, McAvoy JW. 2005. Growth Factor Regulation Of Lens Development. Dev. Biol. 280:1-14.

Chen Y, Stump RJW, Lovicu FJ, McAvoy JW. 2006.A role for Wnt/Planar Cell Polarity signaling during lens fiber cell differentiation? Semin Cell Dev Biol. 17:712-25.

Boros J, Newitt P, Wang Q, McAvoy JW, Lovicu FJ. 2006. Sef and Sprouty expression in the developing ocular lens: implications for regulating lens cell proliferation and differentiation. Semin Cell Dev Biol. 17:741-52.

Pennisi DJ, Wilkinson L, Kolle G, Sohaskey ML, Gillinder K, Piper MJ, McAvoy JW, Lovicu FJ, Little MH. 2007.Crim1KST264/KST264 mice display a disruption of the Crim1 gene resulting in perinatal lethality with defects in multiple organ systems. Dev Dyn. 236:502-11.

Iyengar L, Wang Q, Rasko JEJ, McAvoy JW, Lovicu FJ. 2007. The duration of MAPK/ERK1/2 phosphorylation induced by FGF or ocular media determines lens cell fate. Differentiation. 75:662-668.

O'Connor MD, Wederell ED, de Iongh R, Lovicu FJ, McAvoyJW. 2008. Generation of transparency and cellular organization in lens explants. Exp Eye Res. 86:734-745.

Chen Y, Stump RJW, Lovicu FJ, Shimono A, McAvoy JW. 2008. Wnt signaling is required for organization of the lens fiber cell cytoskeleton and development of lens three-dimensional architecture. Developmental Biology.324:161-176.

Chong CC, Stump RJ, Lovicu FJ, McAvoy JW. 2009. TGFß promotes Wnt expression during cataract development. Exp Eye Res. 88:307-313.

Wang Q, Stump R, McAvoy JW, Lovicu FJ. 2009. MAPK/ERK1/2 and PI3-kinase signalling pathways are required for vitreous-induced lens fibre cell differentiation. Exp Eye Res. 88: 293-306.

Iyengar L, Patkunanathan B, McAvoy JW, Lovicu FJ. (2009). Growth factors involved in aqueous humour-induced lens cell proliferation. Growth Factors.27:50-62.

Sugiyama Y, Stump RJW, Nguyen A, Chen Y, Lovicu FJ, McAvoy JW. 2010. Planar cell polarity orchestrates three-dimensional cellular architecture of the eye lens.Dev Biol. 338:193-201.

Wang Q, McAvoy JW, Lovicu FJ. 2010. Growth factor signalling in vitreous-induced lens fiber differentiation.IOVS, 51:3599-3610.

Newitt P, Boros J, Madakashira BP, Robinson ML, Reneker LW, McAvoy JW, Lovicu FJ. 2010. Sef is a negative regulator of fiber cell differentiation in the ocular lens. Differentiation, 80: 53-67.

Lovicu FJ, McAvoy JW, de Iongh RU. 2010. Understanding the role of growth factors in embryonic development: insights from the lens. Philosophical Transactions B. (review).


Growth factor-induced lens cell proliferation and differentiation regulating ocular lens development and growth.

Primary supervisor: Frank Lovicu

Research in our laboratory is directed at identifying the molecular mechanisms that regulate eye lens development, growth and pathology. Using a range of techniques (including tissue culture, immunohistochemistry, in situ hybridisation, PCR, chromatography, Western blotting, light and electron microscopy, in vitro biological assays and transgenic mouse strategies), we investigate the expression, effects and function of different growth factors and their receptors as well as the regulation of their intracellular signalling, both in normal lens development and pathology. To date, we have shown that members of the fibroblast growth factor (FGF) and Wnt families are important regulators of lens epithelial cell proliferation, migration and differentiation and are important for the normal development and maintenance of the lens.

Students that undertake Honours projects in our laboratory can expect to be exposed to a wide array of techniques, encompassing cellular, developmental and molecular biology, and can carry out a project in one or a combination of the following areas:

Normal Lens Biology

*Investigate the role of growth factors (FGF, PDGF, IGF, EGF, BMPs) and their signalling pathways in regulating lens cell proliferation and fibre differentiation using lens epithelial explants and/or transgenic mouse models.

*Identify factors (related to Wnt signalling) that maintain the normal lens epithelial phenotypic characteristics including cell-cell and cell-matrix adhesion and communication.

*Use transgenic mice and in vitro assays to determine the role of novel genes (Crim1, Sef, Sprouty1/2, Spreds1/2/3) thought to be involved in regulation of growth factor bioavailability and signalling.

*Use electron microscopy and tissue culture to identify the molecules in the ocular fluid that are important for lens cell differentiation and how this contributes to lens transparency.


Discipline: Anatomy & Histology
Co-supervisors: John McAvoy
Keywords: Lens development, growth factors, Cell biology
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