Professor
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Department of Biomedical Genetics (SMD) - Joint
Professor
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Center for Visual Science A&S (RC) - Joint
Professor
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Department of Pathology and Laboratory Medicine (SMD) - Joint
Credentials
Post-doctoral Training & Residency
Postdoctoral Fellow in Dr. Simon John's Laboratory. The Jackson Laboratory, Bar Harbor, ME. Neurodegeneration in Glaucoma. 2001 - 2005
Education
Doctorate in Biology | Boston College.1997
Bachelor of Science in Biology | Villanova University.0
Awards
The Thomas R. Lee Award for National Glaucoma Research.2020
Graduate Student Society Advocacy Award.2020
Shaffer Prize for Research.2017
University of Rochester School of Medicine & Dentistry Trainee Academic Mentoring Award in Basic Science..2013
Research to Prevent Blindness Career Development Award.2006 - 2010
Donald J. White Teaching Excellence Award..1993 - 1997
Research
Research Overview Glaucoma is a complex group of diseases where many different genetic and environmental factors conspire to cause vision loss. While there are many different causes of glaucoma, the ultimate cause of vision loss in all glaucomas is the death of retinal ganglion cells (RGCs), the ...
Research Overview Glaucoma is a complex group of diseases where many different genetic and environmental factors conspire to cause vision loss. While there are many different causes of glaucoma, the ultimate cause of vision loss in all glaucomas is the death of retinal ganglion cells (RGCs), the output neurons of the retina. Therefore, glaucoma is a neurodegeneration. Our lab focuses on the neurobiology of glaucoma. Primarily, we use mouse models of glaucoma and advanced mouse genetics to probe the pathophysiology of glaucoma. Specifically, we are interested in understanding the molecular processes that lead to RGC death in glaucoma and why are RGCs more likely to die in some patients than in others.
Cell Death Pathways Active in Glaucoma To date, no molecules are known to be necessary for glaucomatous neurodegeneration nor has the initial molecular trigger(s) been identified. Identifying the molecular pathways required for RGC death in glaucoma will answer fundamental questions about neuronal pathophysiology and will identify potential therapeutic targets for the treatment of optic neuropathies. To determine the molecular degeneration cascades active in glaucoma we are taking two approaches. (1) Candidate gene analysis. The neurotrophic deprivation pathway (as one example) has been implicated as a critical pathway for glaucomatous RGC death. At both the protein and RNA level, we found that components of this pathway (e.g. BIM, JUN, and JNKs) are present in glaucomatous DBA/2J mice, suggesting that this pathway contributes to RGC death. Currently using our knowledge of the key mediator of somal apoptosis in DBA/2J glaucoma (BAX activation) and the other molecules that have been impacted in glaucoma, we are attempting to 'back track' our way up the RGC degeneration pathway. Eventually we hope this approach will lead to a complete identification of the somal and axonal degeneration pathways and to the initial molecular trigger(s) in glaucoma. (2) Genomic analysis. We are also using microarray analysis to investigate DBA/2J glaucoma. Microarray analysis has the potential to identify molecules involved in glaucomatous neurodegeneration that could not be predicted from current knowledge. In these experiments, gene expression changes at various, distinct stages of DBA/2J glaucomatous neurodegeneration are being examined.
Neuronal Susceptibility Factors Elevated intraocular pressure is the best known risk factor for glaucoma. However, there is extensive patient variability in what constitutes pathogenic intraocular pressure (IOP), suggesting that other susceptibility factors are important in glaucoma. Therefore, even though glaucoma is clearly associated with IOP, susceptibility factors intrinsic to the RGCs and/or other retinal cells are likely critical mediators of glaucomatous neurodegeneration. We are attempting to define the genetic susceptibility factors that conspire with IOP to determine the probability of developing glaucoma and/or the severity of glaucoma. For instance we have shown that deficiencies in BAX gene dosage (a key molecule in the glaucomatous RGC degeneration pathway) can slow RGC loss in glaucomatous mice. These data suggest that allelic differences in components of the RGC degeneration pathway may contribute to glaucoma pathology. Also, we have been addressing the effect of blood pressure on glaucoma by backcrossing a null allele of angiotensin receptor 1 (Agtr1; deficiency in Agtr1 lowers blood pressure in mice) into DBA/2J. Low blood pressure in DBA/2J mice significantly increases the rate of glaucomatous neurodegeneration. Therefore, it appears that many diverse genetic factors can contribute to glaucomatous neurodegeneration and that the DBA/2J mouse is an effective tool in identifying these factors.
Wang X, Lou N, Eberhardt A, Yang Y, Kusk P, Xu Q, Förstera B, Peng S, Shi M, Ladrón-de-Guevara A, Delle C, Sigurdsson B, Xavier ALR, Ertürk A, Libby RT, Chen L, Thrane AS, Nedergaard M
Science translational medicine.. 2020 March 2512 (536)Epub 1900 01 01.
Apara A, Galvao J, Wang Y, Blackmore M, Trillo A, Iwao K, Brown DP, Fernandes KA, Huang A, Nguyen T, Ashouri M, Zhang X, Shaw PX, Kunzevitzky NJ, Moore DL, Libby RT, Goldberg JL
The Journal of neuroscience : the official journal of the Society for Neuroscience.. 2017 October 437 (40):9632-9644. Epub 09/04/2017.
Howell GR, Soto I, Zhu X, Ryan M, Macalinao DG, Sousa GL, Caddle LB, Macnicoll KH, Barbay JM, Porciatti V, Anderson MG, Smith RS, Clark AF, Libby RT, John SW
The Journal of clinical investigation.. 2012 April 122 (4):1246-61. Epub 03/19/2012.
Howell GR, Macalinao DG, Sousa GL, Walden M, Soto I, Kneeland SC, Barbay JM, King BL, Marchant JK, Hibbs M, Stevens B, Barres BA, Clark AF, Libby RT, John SW
The Journal of clinical investigation.. 2011 April 121 (4):1429-44. Epub 03/07/2011.
