Jeremy Sivak
PhD
Open to recruiting graduate students (MSc and PhD)
Jeremy Sivak is a Senior Scientist and holds the Glaucoma Research Chair at the Krembil Research Institute, University Health Network, and is Associate Professor in the University of Toronto School of Medicine.
Dr Sivak completed his PhD in 2001 at Tufts University/New England Medical Center, followed by a postdoctoral fellowship at the University of Cambridge.
He then joined Novartis in 2005 where he led multidisciplinary ophthalmic drug discovery teams.
Dr Sivak returned to academics in 2010 to establish a research program that examines the molecular mechanisms controlling retinal injury responses, and to design new treatment and drug delivery strategies.
The success of this work is reflected in support from federal and non-profit granting agencies, industry collaborations, prominent journal publications, and broad lecturing internationally.
Research Synopsis
Our laboratory is investigating the molecular pathways directing cellular responses to tissue damage and repair in the eye.
This work has direct relevance to retinal degenerative diseases, and also serves as a model for these mechanisms in the central nervous system and other organs.
We have recently turned our attention to damage of the inner retinal layers and optic nerve. Injury to these tissues drives the vision loss for patients with glaucoma; a leading cause of blindness in Canada and worldwide.
We are focusing on the molecular mechanisms that metabolic, oxidative, and biomechanical stress induce in sensitive retinal ganglion cell neurons and their associated glia.
Our goal is to use this information to design new and improved neuroprotective strategies. For these experiments we employ a variety of cutting edge molecular, cellular, pharmacologic, and genetic techniques.
The laboratory currently has openings for trainees and interested applicants should contact me directly.
Selected Publications
Guo, X., Jiang, Q., Tuccitto, A., Chan, D., Alqawlaq, S., Won, G.J., and J.M., S. (2018). The AMPK-PGC-1α Signaling Axis Regulates the Astrocyte Glutathione System to Protect Against Oxidative and Metabolic Injury. Neurobiol of Disease, In Press.
Livne-Bar, I., Wei, J., Liu, H.H., Alqawlaq, S., Won, G.J., Tuccitto, A., Gronert, K., Flanagan, J.G., and Sivak, J.M. (2017). Astrocyte-derived lipoxins A4 and B4 promote neuroprotection from acute and chronic injury. The Journal of Clinical Investigation. pii: 77398. doi: 10.1172/JCI77398.
Exler, R.E., Guo, X., Chan, D., Livne-Bar, I., Vicic, N., Flanagan, J.G., and Sivak, J.M. (2016). Biomechanical insult switches PEA-15 activity to uncouple its anti-apoptotic function and promote erk mediated tissue remodeling. Exp Cell Res 340, 283-294.
Livne-Bar, I., Lam, S., Chan, D., Guo, X., Askar, I., Nahirnyj, A., Flanagan, J.G., and Sivak, J.M. (2016). Pharmacologic inhibition of reactive gliosis blocks TNF-alpha-mediated neuronal apoptosis. Cell Death & Disease 7, e2386.
Guo, X., Dason, E.S., Zanon-Moreno, V., Jiang, Q., Nahirnyj, A., Chan, D., Flanagan, J.G., and Sivak, J.M. (2014). PGC-1alpha signaling coordinates susceptibility to metabolic and oxidative injury in the inner retina. Am J Pathol 184, 1017-1029.
Alqawlaq, S., Sivak, J.M., Huzil, J.T., Ivanova, M.V., Flanagan, J.G., Beazely, M.A., and Foldvari, M. (2014). Preclinical development and ocular biodistribution of gemini-DNA nanoparticles after intravitreal and topical administration: Towards non-invasive glaucoma gene therapy. Nanomedicine: nanotechnology, biology, and medicine.
Mainolfi, N., Powers, J., Amin, J., Long, D., Lee, W., McLaughlin, M.E., Jaffee, B., Brain, C., Elliott, J., and Sivak, J.M. (2013). An effective prodrug strategy to selectively enhance ocular exposure of a cannabinoid receptor (CB1/2) agonist. J Med Chem 56, 5464-5472.
Nahirnyj, A., Livne-Bar, I., Guo, X., and Sivak, J.M. (2013). ROS Detoxification and Proinflammatory Cytokines Are Linked by p38 MAPK Signaling in a Model of Mature Astrocyte Activation. PLoS One 8, e83049.
Sivak, J.M. (2013). The aging eye: common degenerative mechanisms between the Alzheimer's brain and retinal disease. Invest Ophthalmol Vis Sci 54, 871-880.
Rogers, R.S., Dharsee, M., Ackloo, S., Sivak, J.M., and Flanagan, J.G. (2012). Proteomics analyses of human optic nerve head astrocytes following biomechanical strain. Mol Cell Proteomics 11, M111 012302.
Honours and Awards
Glaucoma Research Chair, Krembil Research Institute