Animal models of diseases have been used extensively to study the disease process as well as to test therapeutic interventions. However, in many cases these rodent models do not provide a system which mimic the human disease completely. Moreover it is important to reduce the use of animals in scientific research and use equally robust in vitro culture system. We propose to derive patient specific induced pluripotent stem cells from patients with amyotrophic lateral sclerosis (ALS). We will use dermal fibroblast cells from patients who have ALS (caused by mutations in the angiogenin gene) to derive induced pluripotent stem cells. We will then induce these iPS cells to differentiate into motor neurons and study their cellular and molecular phenotype to understand Ang mediated ALS. This will provide a robust model system to study ALS and replace animal models for Ang mediated ALS.
Ferguson R & Subramanian V (2016) PA6 stromal cell co-culture enhances SH-SY5Y and VSC4.1 neuroblastoma differentiation to mature phenotypes. PLoS One 11(7):e0159051 doi:10.1371/journal.pone.0159051
Thiyagarajan N, Ferguson R, Subramanian V, Acharya KR (2012) Structural and molecular insights into the mechanism of action of human angiogenin-ALS variants in neurons. Nat. Commun. 3:1121 doi:10.1038/ncomms2126