Elizabeth M. Simpson
The overall goal of my research is to develop gene-based therapies for diseases of the brain and eye. My immediate goal is to use recombinant adeno-associated viruses to deliver therapies for treatment of mouse models of human disease. Currently, we are developing cell-type-specific promoters to use in viruses, engineering better mouse models, and developing gene augmentation and genome editing (CRISPR/Cas9) therapies focused on curing the congenital blindness aniridia.
We still have only a cursory understanding of the 98% of the human genome that is non-coding, although we do know that it contains large complex gene promoters. By harnessing this regulatory potential into “MiniPromoters” (small selected regions of human promoters), to drive gene expression in defined cell types of the brain and eye, we are improving the efficacy and safety of gene therapy.
We need new humanized mouse models engineered so that genome editing therapies will bind human DNA, and thus provide proof of principle in treating disease, but also be immediately translatable to human cells and patients. For these new mouse models, currently under development, we have coined the term CHuMMMs (CRISPR humanized-minimally mouse models).
Aniridia is a rare, congenital, panocular, eye disorder. Individuals with aniridia are typically born with low vision, and because there is no effective treatment, subsequently become blind. Research by our lab, and others, have shown that there is a therapeutic window available to limit vision loss. Our short-term goal is to cure the mouse model of aniridia to lay the conceptual and practical foundation upon which human gene therapy can be designed.
MAJOR ACHIEVEMENTS & PUBLICATIONS
As part of a collaborative team, Dr. Simpson’s laboratory restored visual function in a mouse model of complete congenital stationary night blindness (Scalabrino et al., 2015). – 2015
Genome British Columbia Award for Scientific Excellence (LifeSciences BC) – 2014
Canada Research Chair, Tier II, Genetics & Behaviour – 2001-2010
Patents Issued, 5; Provisional Patent Applications, 8; Licences, 3.
AAV-Compatible MiniPromoters for Restricted Expression in the Brain and Eye. de Leeuw, C.N.d., Korecki, A.J., Berry, G.E., Hickmott, J.W., Lam, S.L., Lengyell, T.C., Bonaguro, R.J., Borretta, L., Chopra, V., Chou, A.Y., D’Souza, C.A., Kaspieva, O., Laprise, S., McInerny, S.C., Portales-Casamar, E., Swanson-Newman, M.I., Wong, K., Yang, G.S., Zhoua, M., Jones, S.J.M., Holt, R.A., Asokan, A., Goldowitz, D., Wasserman, W.W., and Simpson, E.M. (2016). Molecular Brain, 9(1):52, Impact Factor 3.617, Cited 3, PMID 27164903.
PAX6 MiniPromoter Drive Restricted Expression from rAAV in the Adult Mouse Retina. Hickmott, J., Chen, C.-y., Arenillas, D.J., Korecki, A.J., Lam, S.L., Molday, L.L., Bonaguro, R.J., Zhou, M., Chou, A.Y., Mathelier, A., Boye, S.L., Hauswirth, W.W., Molday, R.S., Wasserman, W.W., and Simpson, E.M. (2016). Molecular Therapy – Methods & Clinical Development, 3: 16051, Impact Factor Not Yet Assigned, PMID 27556059.
Co-activator candidate interactions for the orphan nuclear receptor NR2E1. Corso-Díaz, X., de Leeuw, C., Alonso, V., Melchers, D., Wong, B.K., Houtman, R., and Simpson, E.M. (2016). BMC Genomics, 17(1): 832, Impact Factor 3.867, PMID 27782803.