RPE Development, Pigmentation and Regeneration
Previous work in our laboratory focused on identifying novel regulators of RPE development and pigmentation, and generating zebrafish models of ocular and oculocutaneous albinism. From these studies, we identified a role for the vacuolar ATPase complex during RPE pigmentation (Nuckels et al., 2009; Shine et al., 2014), and a role for de novo purine synthesis during pigmentation, wherein a GTP-dependent pathway modulates pigment synthesis (Ng et al., 2009). Recently, we identified a zebrafish model of Hermansky-Pudlak Syndrome Type 5, and a role for the N-terminal WD40 repeat of the hps5 protein in stabilizing its interactions with hps6 in the BLOC2 complex, a well-known regulator of melanosome formation (Daly et al., 2013). From our forward genetic screen, we have identified a mutation in nsfb that results in pigmentation defects and we are currently characterizing defects in this mutant to determine how nsfb functions during melanosome formation. Recently, we have initiated a series of studies to examine RPE regeneration. Finally, we are collaborating with Brian Brooks, M.D. Ph.D. at the National Eye Institute to develop zebrafish ocular and oculocutaneous albinism models for use as a screening tool for pharmacological therapies that lead to increased pigment synthesis.