Catherine Tsilfidis, PhD

ctsilfidis@ohri.ca

Senior Scientist, Regenerative Medicine, Ottawa Hospital Research Institute

Associate Professor - Departments of Ophthalmology and Cellular and Molecular Medicine, University of Ottawa
Don and Joy Maclaren Chair for Vision Research

Biographical Sketch

I obtained my Ph. D. from the University of Toronto, working in Richard Liversage's laboratory in the area of developmental biology. My project examined the effects of nerves on Xenopus laevis forelimb regeneration. Post-doctoral studies were carried out at the Children's Hospital of Eastern Ontario in Robert Korneluk's laboratory. Our team was one of several which discovered the gene which causes myotonic dystrophy, a form of muscular dystrophy. From 1993 to April, 2000 I was a researcher at the Eye Institute in Toronto (with appointments to the Departments of Ophthalmology and Zoology at the University of Toronto). Projects in my lab involved a genetic analysis of autosomal dominant congenital cataracts and the molecular aspects of forelimb regeneration in the newt, Notophthalmus viridescens. I have been at the OHRI (at the University of Ottawa Eye Institute) since April, 2000.

Research Interests

  • Molecular aspects of forelimb and lens regeneration in the newt, Notophthalmus viridescens
  • Dedifferentiation as a source of stem cells in the regeneration process
  • Gene therapy in retinal degeneration using XIAP, a potent inhibitor of apoptosis
  • Stem cell applications to retinal damage or disease

Major Research Activities

There are two major research focuses in the lab.

Research Focus I: Regeneration in the newt, Notophthalmus viridescens.

Amphibians such as the newt, Notophthalmus viridescens, have a unique ability to regenerate arms legs, spinal cord, eye structures and many vital organs. Through a process called epimorphic regeneration, structures lost to injury or amputation are replaced, such that the regenerated structure is indistinguishable from the original. An understanding of the basic mechanisms involved in these processes will not only advance our fundamental knowledge of the biology of regeneration, but will also have considerable clinical implications for humans. The most critical stage in the regeneration response, and the reason why some amphibians possess the ability to regenerate, is their ability to induce the tissues at the site of injury to revert to an embryonic-like state - a process called dedifferentiation. An understanding of the molecular mechanisms involved in dedifferentiation is essential in order to enhance the regenerative ability in non-regenerating animals.

One of the major research aims of my laboratory is to identify factors controlling the onset of dedifferentiation so that we may use these factors to improve regenerative potential in man. We have used representational difference analysis (RDA) to isolate genes which may play key roles during dedifferentiation. Characterizing these genes is a central focus of our research.

Research Focus II: Gene and stem cell therapy in animal models of retinal degeneration

Inherited retinal degenerations lead to a progressive loss of vision. Most often, they are characterized by a gradual loss of the photoreceptors in the retina. Cell death occurs through the process of apoptosis. We believe that regardless of the genetic mutation which a cell possesses, if we can target and prevent the ultimate death of the cell, we will be able to retain function in the retinal cells and prevent vision loss. We are using inhibitors of apoptosis (IAPs) to try to prevent the retinal degeneration which is associated with diseases such as retinitis pigmentosa, retinal ischemia, or glaucoma. XIAP (the X-linked inhibitor of apoptosis protein) prevents apoptosis by blocking the action of caspases, which are enzymes that are involved in the cell death pathway. We have over-expressed XIAP in the retina and shown that it protects photoreceptors in animal models of retinal ischemia, retina detachment and retinitis pigmentosa. These results hold tremendous promise for the treatment of human retinal diseases. Current studies are aimed at developing XIAP therapy for clinical application.

Current Funding Sources

04/2010 - 03/2015 -   Canadian Institutes of Health Research (CIHR) - Emerging Team Grant
04/2010 - 03/2015 -   Foundation Fighting Blindness (FFB)
04/2008 - 03/2013 -   Natural Sciences and Engineering Research Council of Canada (NSERC)
12/2012     Ottawa Hospital Foundation
11/2012 10/2013  Krembil Foundation/FFB

Publications:

Fong, WG, Tsilfidis C (2012). Retinal Degeneration and Cellular Suicide. Adv. Exp. Med. Biol. 723: 207-14.

Beddaoui M, Coupland SG, Tsilfidis C (2012). Recovery of function following regeneration of the damaged retina in the adult newt, Notophthalmus viridescens. Doc Ophthalmol. 125(2): 91-100.

Yao J, Feathers KL, Khanna H, Thompson DA, Tsilfidis C, Hauswirth WW, Heckenlively JR, Swaroop A, Zacks DN (2010). XIAP Therapy Increases Survival of Transplanted Rod Precursors in a Degenerating Host Retina. Invest. Ophthal. Vis. Sci. Oct 6. [Epub ahead of print].

Rafat, M., Cleroux, C., Fong W.G., Baker A., Leonard B., O'Connor M., and C. Tsilfidis (2010). PEG-PLA Microparticles for Encapsulation and Delivery of Tat-EGFP to Retinal Cells. Biomaterials 31: 3414-3421.

Zadro-Lamoureux, L.A., D.N. Zacks, A.N. Baker, Q.-D. Zheng, W.W. Hauswirth, and C. Tsilfidis (2009). XIAP effects on retinal detachment-induced photoreceptor apoptosis. Invest. Ophthal. Vis. Sci. 50(3):1448-53.

Leonard, K.C., D. Petrin, S. G. Coupland, A. N. Baker, B. C. Leonard, W. W. Hauswirth, R. G. Korneluk and C. Tsilfidis (2007). XIAP Protection of Photoreceptors in Animal Models of Retinitis Pigmentosa. PLoS ONE Mar 21; 2:e314.

Chaar, Z.Y. and C. Tsilfidis (2006). Newt opportunities for understanding the dedifferentiation process (review). TheScientificWorld Development and Embryology 1(S1): 55-64.