Welcome

Research in the Kiser lab is broadly focused on metabolic processing of retinoids and carotenoids with an emphasis on how such transformations support vision. One line of inquiry concerns a biochemical pathway, known as the visual or retinoid cycle, that produces the 11-cis-retinal chromophore needed to regenerate the visual pigments our rod and cone photoreceptors use to detect light. Our research is devoted to understanding the mechanisms underlying visual cycle function as well as the physiologic roles of ancillary 11-cis-retinal biosynthetic pathways. We are also interested in uncovering mechanisms of visual cycle-associated retinal diseases and developing agents (primarily small molecules) that modulate visual cycle activity for therapeutic use in conditions such as Stargardt disease and age-related macular degeneration. Our work integrates findings from in vivo studies of animal models, cell-based model systems, pharmacologic and biochemical studies, and structural biology to develop a comprehensive understanding of retinoid processing in the retina. Beyond the biochemistry of retinoids, we have also contributed to structural understanding of proteins involved in phototransduction. A recent focus has been on the structural biology of beta-arrestins, which are essential for controlling the duration of visual pigment signaling. Another facet of our research is on the molecular enzymology of a family of enzymes known as carotenoid cleavage dioxygenases. In relation to vision in animals, these enzymes are essential for the conversion of pro-vitamin A carotenoids into retinoids as well as the formation of 11-cis-retinoids. Not limited to metazoa, these enzymes play essential roles in plant physiology and enable photon detection in cyanobacteria, amongst other functions. We collaborate with biophysicists, spectroscopists, medicinal chemists, and clinicians to achieve our experimental goals. Our work is funded by the National Eye Institute, the Department of Veterans Affairs, the National Science Foundation, and Research to Prevent Blindness.