Currently, we work collaboratively with the Palczewski and Kiser labs understanding the visual cycle. We are interested in gaining a mechanistic understanding of how retinoids (and drugs affecting vision) utilize the cellular machinery comprising the visual cycle. Specifically, we are actively studying the mechanism by which RPE65 is able to isomerize all-trans-retinyl esters to 11-cis-retinol, and the implications of these findings on the drug candidate Emixustat. Additionally, we are interested in how the formate esters of retinoids can form covalent adducts with the apo form of opsin.

a. Kahremany S, Kubas A, Tochtrop GP, Palczewski K. Catalytic synthesis of 9-cis-retinoids: mechanistic insights. Dalton Trans. 2019 Jul 16;48(28):10581-10595.

b. Kiser PD, Zhang J, Sharma A, Angueyra JM, Kolesnikov AV, Badiee M, Tochtrop GP, Kinoshita J, Peachey NS, Li W, Kefalov VJ, Palczewski K. Retinoid isomerase inhibitors impair but do not block mammalian cone photoreceptor function. J Gen Physiol. 2018 150:571-590. PMID: 29500274

c. Kiser PD, Zhang J, Badiee M, Kinoshita J, Peachey NS, Tochtrop GP, Palczewski K. Rational tuning of visual cycle modulator pharmacodynamics. J Pharmacol Exp Ther. 2017:117.240721. PMID: 28476927

d. Gulati S, Jastrzebska B, Banerjee S, Placeres ÁL, Miszta P, Gao S, Gunderson K, Tochtrop GP, Filipek S, Katayama K, Kiser PD, Mogi M, Stewart PL, Palczewski K, Photocyclic behavior of rhodopsin induced by an atypical isomerization mechanism. Proc Natl Acad Sci U S A. 2017 :E2608-E2615 PMID:28289214