Professor John McAvoy
Faculty of Medicine and Health
Clinical Ophthalmology and Eye Health
Save Sight Institute
How a particular tissue or organ develops its characteristic size and three-dimensional cellular architecture is often a poorly understood part of its developmental program; yet, as is clearly the case for the eye lens, precise regulation of these features can be critical for function. During lens morphogenesis cells become organized into a polarized, spheroidal structure with a monolayer of epithelial cells overlying the apical tips of highly elongated fibre cells. Epithelial cells proliferate and progeny that shift below the lens equator differentiate into new fibres that become precisely aligned and oriented towards the poles of the lens as they progressively add to the fibre mass. Research in our laboratory has shown that FGF induces epithelial to fibre differentiation; however, it is not fully understood how the proliferation and differentiation compartments are regulated to ensure appropriate growth and at the same time maintain the highly ordered and polarized three-dimensional lens structure. In recent studies we have shown that planar cell polarity (PCP) operates in the lens and Wnt-Frizzled signalling plays a role in regulating the polarized cell behaviour that is critical for normal lens morphogenesis and growth. We believe that the lens will be a useful model system to study Wnt-Frizzled/PCP in general and gain insights into mechanisms that generate high-level cellular order during development.
Selected publications
Publications
Books
- Pandey, S., Apple, D., Werner, L., McAvoy, J., Maloof, A., Milverton, E. (2005). Posterior Capsule Opacification. India: Jaypee Brothers Medical Publishers.
Book Chapters
- Lovicu, F., Iyengar, L., Dawes, L., McAvoy, J. (2014). Lens Epithelial Cell Proliferation. In Shizuya Saika, Liliana Werner, Frank J. Lovicu (Eds.), Lens Epithelium and Posterior Capsular Opacification, (pp. 59-80). Tokyo, Japan: Springer. [More Information]
- Sugiyama, Y., McAvoy, J. (2012). Analysis of PCP defects in mammalian eye lens. In Kursad Turksen (Eds.), Methods in Microbiology: Planar Cell Polarity, (pp. 147-156). New York: Humana Press. [More Information]
- Lovicu, F., McAvoy, J. (2008). Epithelial explants and their application to study developmental processes in the lens. In P A Tsonis (Eds.), Animal Models in Eye Research, (pp. 134-147). United States: Academic Press.
Journals
- Dawes, L., Shelley, E., McAvoy, J., Lovicu, F. (2018). A role for Hippo/YAP-signaling in FGF-induced lens epithelial cell proliferation and fibre differentiation. Experimental Eye Research, 169, 122-133. [More Information]
- Piatigorsky, J., Bassnett, S., McAvoy, J., Bhat, S. (2017). David C. Beebe, 1944–2015, in memoriam. Experimental Eye Research, 156, 3-4. [More Information]
- McAvoy, J., Dawes, L., Sugiyama, Y., Lovicu, F. (2017). Intrinsic and extrinsic regulatory mechanisms are required to form and maintain a lens of the correct size and shape. Experimental Eye Research, 156, 34-40. [More Information]
Patents
- McAvoy, J., Chamberlain, C. (2006). A Method For Preventing Or Controlling Cataract. Patent No. 735895. , Austria, Belgium, Denmark, France, Germany, Greece, Ireland, Italy, Liechtenstein, Luxembourg, Monaco, Netherlands, Portugal, Spain, Sweden, Switzerland, United Kingdom.
2018
- Dawes, L., Shelley, E., McAvoy, J., Lovicu, F. (2018). A role for Hippo/YAP-signaling in FGF-induced lens epithelial cell proliferation and fibre differentiation. Experimental Eye Research, 169, 122-133. [More Information]
2017
- Piatigorsky, J., Bassnett, S., McAvoy, J., Bhat, S. (2017). David C. Beebe, 1944–2015, in memoriam. Experimental Eye Research, 156, 3-4. [More Information]
- McAvoy, J., Dawes, L., Sugiyama, Y., Lovicu, F. (2017). Intrinsic and extrinsic regulatory mechanisms are required to form and maintain a lens of the correct size and shape. Experimental Eye Research, 156, 34-40. [More Information]
2016
- Lovicu, F., Shin, E., McAvoy, J. (2016). Fibrosis in the lens. Sprouty regulation of TGFbeta-signaling prevents lens EMT leading to cataract. Experimental Eye Research, 142, 92-101. [More Information]
- Sugiyama, Y., Shelley, E., Yoder, B., Kozmik, Z., May-Simera, H., Beales, P., Lovicu, F., McAvoy, J. (2016). Non-essential role for cilia in coordinating precise alignment of lens fibres. Mechanisms of Development, 139, 10-17. [More Information]
2015
- Sugiyama, Y., Shelley, E., Badouel, C., McNeill, H., McAvoy, J. (2015). Atypical Cadherin Fat1 Is Required for Lens Epithelial Cell Polarity and Proliferation but Not for Fiber Differentiation. Investigative Ophthalmology and Visual Science, 56(6), 4099-4107. [More Information]
- Zhao, G., Wojciechowski, M., Jee, S., Boros, J., McAvoy, J., Lovicu, F. (2015). Negative regulation of TGFβ-induced lens epithelial to mesenchymal transition (EMT) by RTK antagonists. Experimental Eye Research, 132, 9-16. [More Information]
2014
- Dawes, L., Sugiyama, Y., Lovicu, F., Harris, C., Shelley, E., McAvoy, J. (2014). Interactions between lens epithelial and fiber cells reveal an intrinsic self-assembly mechanism. Developmental Biology, 385(2), 291-303. [More Information]
- Lovicu, F., Iyengar, L., Dawes, L., McAvoy, J. (2014). Lens Epithelial Cell Proliferation. In Shizuya Saika, Liliana Werner, Frank J. Lovicu (Eds.), Lens Epithelium and Posterior Capsular Opacification, (pp. 59-80). Tokyo, Japan: Springer. [More Information]
2013
- Wang, C., Dawes, L., Liu, Y., Wen, L., Lovicu, F., McAvoy, J. (2013). Dexamethasone influences fgf-induced responses in lens epithelial explants and promotes the posterior capsule coverage that is a feature of glucocorticoid-induced cataract. Experimental Eye Research, 111, 79-87. [More Information]
- Sugiyama, Y., Shelley, E., Wen, L., Stump, R., Shimono, A., Lovicu, F., McAvoy, J. (2013). Sfrp1 and Sfrp2 are not involved in Wnt/β-catenin signal silencing during lens induction but are required for maintenance of Wnt/β-catenin signaling in lens epithelial cells. Developmental Biology, 384(2), 181-193. [More Information]
- You, J., Hodge, C., Wen, L., McAvoy, J., Madigan, M., Sutton, G. (2013). Tear levels of SFRP1 are significantly reduced in keratoconus patients. Molecular Vision, 19, 509-515. [More Information]
2012
- Sugiyama, Y., McAvoy, J. (2012). Analysis of PCP defects in mammalian eye lens. In Kursad Turksen (Eds.), Methods in Microbiology: Planar Cell Polarity, (pp. 147-156). New York: Humana Press. [More Information]
- Madigan, M., You, J., Wen, L., Hodge, C., Roufas, A., McAvoy, J., Sutton, G. (2012). Secreted frizzled proteins in control and keratoconus (KC) tears and corneas. Acta Ophthalmologica, 90(Supplement s249). [More Information]
- Shin, E., Basson, M., Robinson, M., McAvoy, J., Lovicu, F. (2012). Sprouty Is a Negative Regulator of Transforming Growth Factor B-induced Epithelial-to-Mesenchymal Transition and Cataract. Molecular Medicine, 18, 861-873. [More Information]
2011
- Sugiyama, Y., Lovicu, F., McAvoy, J. (2011). Planar cell polarity in the mammalian eye lens. Organogenesis, 7(3), 191-201. [More Information]
- Kallifatidis, G., Boros, J., Shin, E., McAvoy, J., Lovicu, F. (2011). The fate of dividing cells during lens morphogenesis, differentiation and growth. Experimental Eye Research, 92(6), 502-511. [More Information]
- Lovicu, F., McAvoy, J., de Iongh, R. (2011). Understanding the role of growth factors in embryonic development: insights from the lens. Philosophical Transactions of the Royal Society B, 366(1568), 1204-1218. [More Information]
2010
- Wang, Q., McAvoy, J., Lovicu, F. (2010). Growth Factor Signaling in Vitreous Humor-Induced Lens Fiber Differentiation. Investigative Ophthalmology and Visual Science, 51(7), 3599-3610. [More Information]
- Sutton, G., Madigan, M., Roufas, A., McAvoy, J. (2010). Secreted frizzled-related protein 1 (SFRP1) is highly upregulated in keratoconus epithelium: a novel finding highlighting a new potential focus for keratoconus research and treatment. Clinical and Experimental Ophthalmology, 38(1), 43-48. [More Information]
- Sugiyama, Y., Stump, R., Nguyen, A., Wen, L., Chen, Y., Murdoch, J., Lovicu, F., McAvoy, J. (2010). Secreted frizzled-related protein disrupts PCP in eye lens fiber cells that have polarised primary cilia. Developmental Biology, 338(2), 193-201. [More Information]
2009
- Iyengar, L., Patkunanathan, B., McAvoy, J., Lovicu, F. (2009). Growth factors involved in aqueous humour-induced lens cell proliferation. Growth Factors, 27(1), 50-62. [More Information]
- Wang, Q., Stump, R., McAvoy, J., Lovicu, F. (2009). MAPK/ERK1/2 and PI3-kinase signalling pathways are required for vitreous-induced lens fibre cell differentiation. Experimental Eye Research, 88(2), 293-306. [More Information]
- Sharma, S., Koh, K., Collin, C., Dave, A., mcMellon, A., Sugiyama, Y., McAvoy, J., Voss, A., Gecz, J., Craig, J. (2009). NHS-A isoform of the NHS gene is a novel interactor of ZO-1. Experimental Cell Research, 315(14), 2358-2372. [More Information]
2008
- Lovicu, F., McAvoy, J. (2008). Epithelial explants and their application to study developmental processes in the lens. In P A Tsonis (Eds.), Animal Models in Eye Research, (pp. 134-147). United States: Academic Press.
- O'Connor, M., Wederell, E., de Iongh, R., Lovicu, F., McAvoy, J. (2008). Generation of transparency and cellular organization in lens explants. Experimental Eye Research, 86(5), 734-745. [More Information]
- Chen, Y., Stump, R., Lovicu, F., Shimono, A., McAvoy, J. (2008). Wnt signaling is required for organization of the lens fiber cell cytoskeleton and development of lens three-dimensional architecture. Developmental Biology, 324(1), 161-176. [More Information]
2007
- Jamieson, R., Farrar, N., Stewart, K., Perveen, R., Mihelec, M., Carette, M., Grigg, J., McAvoy, J., Lovicu, F., Tam, P., et al (2007). Characterization of a familial t(16;22) balanced translocation associated with congenital cataract leads to identification of a novel gene, TMEM114, expressed in the lens and disrupted by the translocation. Human Mutation, 28(10), 968-977. [More Information]
- Pennisi, D., Wilkinson, L., Kolle, G., Sohaskey, M., Gillinder, K., Piper, M., McAvoy, J., Lovicu, F., Little, M. (2007). Crim1(KST264/KST264) mice display a disruption of the Crim1 gene resulting in perinatal lethality with defects in multiple organ systems. Developmental Dynamics, 236(2), 502-511. [More Information]
- Iyengar, L., Wang, Q., Rasko, J., McAvoy, J., Lovicu, F. (2007). Duration of ERK1/2 phosphorylation induced by FGF or ocular media determines lens cell fate. Differentiation, 75(7), 662-668. [More Information]
2006
- McAvoy, J., Chamberlain, C. (2006). A Method For Preventing Or Controlling Cataract. Patent No. 735895. , Austria, Belgium, Denmark, France, Germany, Greece, Ireland, Italy, Liechtenstein, Luxembourg, Monaco, Netherlands, Portugal, Spain, Sweden, Switzerland, United Kingdom.
- Chen, Y., Stump, R., Lovicu, F., McAvoy, J. (2006). A role for Wnt/planar cell polarity signaling during lens fiber cell differentiation? Seminars in Cell and Developmental Biology, 17(6), 712-725. [More Information]
- Iyengar, L., Patkunanathan, B., Lynch, O., McAvoy, J., Rasko, J., Lovicu, F. (2006). Aqueous humour- and growth factor-induced lens cell proliferation is dependent on MAPK/ERK1/2 and Akt/PI3-K signalling. Experimental Eye Research, 83(3), 667-678. [More Information]
2005
- Lovicu, F., McAvoy, J. (2005). Growth factor regulation of lens development. Developmental Biology, 280(1), 1-14. [More Information]
- Wederell, E., Brown, H., O'Connor, M., Chamberlain, C., McAvoy, J., de Iongh, R. (2005). Laminin-binding integrins in rat lens morphogenesis and their regulation during fibre differentiation. Experimental Eye Research, 81(3), 326-39. [More Information]
- Pandey, S., Apple, D., Werner, L., McAvoy, J., Maloof, A., Milverton, E. (2005). Posterior Capsule Opacification. India: Jaypee Brothers Medical Publishers.
2004
- Lovicu, F., Steven, P., Saika, S., McAvoy, J. (2004). Aberrant Lens Fiber Differentiation In Anterior Subcapsular Cataract Formation: A Process Dependent On Reduced Levels Of Pax6. Investigative Ophthalmology and Visual Science, 45(6), 1946-1953. [More Information]
- de Iongh, R., Chen, Y., Kokkinos, M., McAvoy, J. (2004). Bmp And Activin Receptor Expression In Lens Development. Molecular Vision, 10(69), 566-576.
- Lovicu, F., Ang, S., Chorazyczewska, M., McAvoy, J. (2004). Deregulation Of Lens Epithelial Cell Proliferation And Differentiation During The Development Of TGFβ-Induced Anterior Subcapsular Cataract. Developmental Neuroscience, 26(5-6), 446-455. [More Information]
2003
- Stump, R., Ang, S., Chen, Y., von Bahr, T., Lovicu, F., Pinson, K., De Iongh, R., Yamaguchi, T., Sassoon, D., McAvoy, J. (2003). A role for Wnt/Beta-catenin signaling in lens epithelial differentiation. Developmental Biology, 259(1), 48-61. [More Information]
2002
- Maruno, K., Lovicu, F., Chamberlain, C., McAvoy, J. (2002). Apoptosis is a feature of TGFb-induced cataract. Clinical and Experimental Optometry, 85(2), 76-82.
- Kok, A., Lovicu, F., Chamberlain, C., McAvoy, J. (2002). Influence of platelet-derived growth factor on lens epithelial cell proliferation and differentiation. Growth Factors, 20(1), 27-34. [More Information]
- Saika, S., Miyamoto, T., Ishida, I., Shirai, K., Ohnishi, Y., Ooshima, A., McAvoy, J. (2002). TGF-Smad signalling in postoperative human lens epithelial cells. British Journal of Ophthalmology, 86(12), 1428-1433.
2001
- Lovicu, F., McAvoy, J. (2001). FGF-induced lens cell proliferation and differentiation is dependent on MAPK (ERK1/1) signalling. Development, 128 (24), 5075-5084.
- De Iongh, R., Lovicu, F., Hardeman, E., McAvoy, J., Overbeek, P., Schneider, M., Joya, J. (2001). Requirement for TGFb receptor signalling during terminal lens fiber differentiation. Development, 128, 3995-4010.
- McAvoy, J., Saika, S., Okada,, Y., Miyamoto, T., Ohnishi, Y., Ooshima,, A. (2001). Smad translocation & growth suppression in lens epithelial cells by endogenous TGFB2 during wound repair. Experimental Eye Research, 72 (6), 679-686.
Selected Grants
2014
- Support for Laboratory Research, Save Sight Institute, McAvoy J, Sydney Medical School/Research Support
- NGC QUEST 10 plus Chromatography System , Gillies M, Shen W, Zhu L, McAvoy J, DVC Research/Equipment Grant
- A role for planar cell polarity in lens regeneration, McAvoy J, Lovicu F, Ophthalmic Research Institute of Australia (ORIA)/Research Support
2012
- The contribution of aberrant Wnt signalling to neuronal and vascular pathology in retinal disease, Gillies M, Shen W, McAvoy J, Zhu L, National Health and Medical Research Council (NHMRC)/Project Grants
- Zeiss Confocal Microscope, LSM700, McAvoy J, Martin P, Gillies M, Grunert U, Watson S, Lovicu F, DVC Research/Equipment Grant