Elizabeth M. Simpson
Therapies for the brain and eye represent a major unmet need, and gene therapy is emerging as a real treatment option, with numerous clinical trials ongoing such as those for macular degeneration, and Alzheimer and Parkinson Disease.
The overall goal of my research is to develop gene-based therapies for diseases of the brain and eye. My approach is to use rAAV (recombinant adeno-associated virus) to deliver therapies to treat mouse models of human disease. Currently, we are mining the human genome for cell-type-specific promoters to use in viruses, and developing gene augmentation and genome editing (CRISPR/cas9) therapies focused on curing the congenital blindness aniridia.
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 lose all vision. Thus, there is a therapeutic window available to prevent vision loss. Our short-term goal is to cure the mouse model of aniridia. Curing aniridia in mice will lay the conceptual and practical foundation upon which human gene therapy can be designed.
We still have only a cursory understanding of the 98% of the human genome that is non-coding. However, we do know that it contains large complex promoters. Understanding and harnessing this regulatory potential into “MiniPromoters” (small selected regions of human promoters), to drive gene expression in defined regions of the brain and eye, is an interest of Dr. Simpson. Such MiniPromoters have many applications for basic and clinical research, but the most demanding and exciting is gene therapy; a promising approach for diseases with unmet therapeutic needs.
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, 7; Provisional Patent Applications, 10; Licences, 3.
Targeted CNS delivery using human MiniPromoters and demonstrated compatibility with adeno-associated viral vectors. de Leeuw, C.N., Dyka, F.M., Boye, S.L., Laprise, S., Zhou, M., Chou, A.Y., Borretta, L.J., McInerny, S.C., Banks, K.G., Portales-Casamar, E., Swanson, M.I., D'Souza, C.A., Boye, S.E., Jones, S.J.M., Holt, R.A., Goldowitz, D., Hauswirth, W.W., Wasserman, W.W., and Simpson, E.M. (2014). Mol Ther Methods Clin Dev 1, 1-15, Impact Factor Not Yet Assigned, Cited 5, PMID 24761428.
Absence of NR2E1 mutations in Patients with Aniridia. Corso-Díaz, X., Borrie, A.E., Bonaguro, R.J., Schuetz, J.M., Rosenberg, T., Jensen, H., Brooks, B.P., MacDonald, I., Pasutto, F., Walter, M., Gronskov, K., Brooks-Wilson, A.R., and Simpson, E.M. (2012). Molecular vision 18, 2770-2782, Impact Factor 1.987, Cited 3, PMID 23213277
Fierce: a new mouse deletion of Nr2e1; violent behaviour and ocular abnormalities are background-dependent. Young, K.A., Berry, M.L., Mahaffey, C.L., Saionz, J.R., Hawes, N.L., Chang, B., Zheng, Q.Y., Smith, R.S., Bronson, R.T., Nelson, R.J., and Simpson, E.M. (2002). Behavioural Brain Research 132, 145-158, Impact Factor 2.791, Cited 104, PMID 11997145.
Genetic variation among 129 substrains and its importance for targeted mutagenesis in mice. Simpson, E.M., Linder, C.C., Sargent, E.E., Davisson, M.T., Mobraaten, L.E., and Sharp, J.J. (1997). Nature Genetics 16, 19-27, Impact Factor 38.854, Cited 625, PMID 9140391.