Philip D Kiser

Picture of Philip D Kiser
Associate Professor, Physiology & Biophysics
School of Medicine
Joint appointment, Ophthalmology
School of Medicine
Joint appointment, Department of Clinical Pharmacy Practice
School of Pharmacy & Pharmaceutical Sciences
Member, Center for Translational Vision Research
Ph.D., Case Western Reserve University, 2010, Pharmacology
Pharm.D., St. Louis College of Pharmacy, 2005, Pharmacy
Phone: 949-824-6954
Fax: 949-824-8540
Email: pkiser@uci.edu
University of California, Irvine
Gillespie Neuroscience Research Facility
RM 2216
837 Health Sciences Rd
Irvine, CA 92617
Research Interests
Vision Science, retinal diseases, retinoid biochemistry, carotenoid oxygenases, pharmacology, crystallography
Research Abstract
My laboratory studies the enzymes, transporters and binding proteins that comprise a metabolic pathway known as the visual cycle as well as a variety of other proteins important for the health of the retina. We use an array of experimental techniques and methodologies, including X-ray crystallography, electron microscopy, knockout mouse models, and classic biochemistry approaches to answer important questions about the structure and function of these proteins. Major emphasis is placed on the use of such information to develop effective therapeutics for currently untreatable retinal diseases.
Awards and Honors
Career Advancement Award, Research to Prevent Blindness, 2024
Fellow of the International Carotenoid Society, 2023
Pisart Award in Vision Science, Lighthouse Guild, 2020
Career Development Award (CDA-2), Department of Veterans Affairs, 2015-2020
March of Dimes Travel Award, FASEB Biology and Chemistry of Vision Conference, 2015
NIH Pediatric Research Loan Repayment Program Award, 2006-2010
Doctoral Excellence Award in Pharmacology, Case Western Reserve University, 2010
Merck Award for Highest Rank Collectively in Pharmacology, Pharmacy Practice, Therapeutics, and Medicinal Chemistry, St. Louis College of Pharmacy, 2004
Publications
Barnes, C. L., Salom, D., Namitz, K., Smith, W. C., Cosgrove, M. S., Kiser, P. D.#, and Calvert, P. D.# (2024) Mechanisms of amphibian arrestin 1 self-association and dynamic distribution in retinal photoreceptors. J. Biol. Chem. accepted
#Co-corresponding
Leinonen, H., Zhang, J., Occelli, L. M., Seemab, U., Choi, E. H., LF, L. P. Marinho, Querubin, J., Kolesnikov, A. V., Galinska, A., Kordecka, K., Hoang, T., Lewandowski, D., Lee, T. T., Einstein, E. E., Einstein, D. E., Dong, Z., Kiser, P. D., Blackshaw, S., Kefalov, V. J., Tabaka, M., Foik, A., Petersen-Jones, S. M., and Palczewski, K. (2024) A combination treatment based on drug repurposing demonstrates mutation-agnostic efficacy in pre-clinical retinopathy models. Nat. Commun. 15, 5943
Solano, Y. J., and Kiser, P. D.# (2024) Double duty isomerases: a case study of isomerization-coupled enzymatic catalysis. Trends Biochem. Sci. accepted
#Corresponding
Solano, Y. J., Everett, M. P., Dang, K. S., Abueg, J., and Kiser, P. D.# (2024) Carotenoid cleavage enzymes evolved convergently to generate the visual chromophore. Nat. Chem. Biol. 20, 779-788
#Corresponding
Bassetto, M., Kolesnikov, A. V., Lewandowski, D., Kiser, J. Z., Halabi, M., Einstein, D. E., Choi, E. H., Palczewski, K., Kefalov, V. J., and Kiser, P. D.# (2024) Dominant role for pigment epithelial CRALBP in supplying visual chromophore to photoreceptors. Cell Rep. 43, 114143
#Corresponding
Hong, J. D., Salom, D., Choi, E. H., Du, S. W., Tworak, A., Smidak, R., Gao, F., Solano, Y. J., Zhang, J., Kiser, P. D., and Palczewski, K. (2024) Retinylidene chromophore hydrolysis from mammalian visual and non-visual opsins. J Biol Chem 300, 105678
Wu, A., Salom, D., Hong, J. D., Tworak, A., Watanabe, K., Pardon, E., Steyaert, J., Kandori, H., Katayama, K., Kiser, P. D.#, and Palczewski, K. (2023) Structural basis for the allosteric modulation of rhodopsin by nanobody binding to its extracellular domain. Nat. Commun. 14, 5209
#Co-corresponding
Schmittou, A. N., Solano, Y. J., Kiser, P. D., and Pierce, B. S. (2023) 3-mercaptopropionate dioxygenase. in Encyclopedia of Inorganic and Bioinorganic Chemistry (Scott, R. A. ed.), John Wiley & Sons, Ltd. 1-36
Luu, J. C., Saadane, A., Leinonen, H., Choi, E. H., Gao, F., Lewandowski, D., Halabi, M., Sander, C. L., Wu, A., Wang, J. M., Singh, R., Gao, S., Lessieur, E. M., Dong, Z., Palczewska, G., Mullins, R. F., Peachey, N. S., Kiser, P. D., Tabaka, M., Kern, T. S., and Palczewski, K. (2023) Stress resilience-enhancing drugs preserve tissue structure and function in degenerating retina via phosphodiesterase inhibition. Proc. Natl. Acad. Sci. U.S.A. 120, e2221045120
Bassetto, M., Zaluski, J., Li, B., Zhang, J., Badiee, M., Kiser, P. D.#, and Tochtrop, G. P.# (2023) Tuning the metabolic stability of visual cycle modulators through modification of an RPE65 recognition motif. J. Med. Chem. 66, 8140-8158
#Co-corresponding
Tworak, A., Kolesnikov, A. V., Hong, J. D., Choi, E. H., Luu, J. C., Palczewska, G., Dong, Z., Lewandowski, D., Brooks, M. J., Campello, L., Swaroop, A., Kiser, P. D., Kefalov, V. J., and Palczewski, K. (2023) Rapid RGR-dependent visual pigment recycling is mediated by the RPE and specialized Muller glia. Cell Rep. 42, 112982
Kiser, P. D.# (2022) Retinal Pigment Epithelium 65 kDa Protein (RPE65): An Update. Prog. Retin. Eye Res. 88, 101013
#Corresponding
Hong, J. D., Salom, D., Kochman, M. A., Kubas, A., Kiser, P. D., and Palczewski, K. (2022) Chromophore Hydrolysis and Release from Photoactivated Rhodopsin in Native Membranes. Proc. Natl. Acad. Sci. U.S.A. 119, e2213911119
Huh, C. Y. L., Leinonen, H., Nakayama, T., Tomasello, J. R., Zhang, J., Zeitoun, J., Peach, J. P., Halabi, M., Kiser, J. Z., Palczewski, K., Kiser, P. D., and Gandhi, S. P. (2022) Retinoid therapy restores eye-specific cortical responses in adult mice with retinal degeneration. Curr. Biol. 32, 1-9
Daruwalla A, Sui X, Kiser PD#. Preparation of carotenoid cleavage dioxygenases for X-ray crystallography. Methods Enzymol. 2022;671:243-271.
#Corresponding
Occelli LM, Daruwalla A, De Silva SR, Winkler PA, Sun K, Pasmanter N, Minella A, Querubin J, Lyons LA; 99 Lives Consortium, Robson AG, Heon E, Michaelides M, Webster AR, Palczewski K, Vincent A, Mahroo OA, Kiser PD, Petersen-Jones SM. A large animal model of RDH5-associated retinopathy recapitulates important features of the human phenotype. Hum Mol Genet. 2022 Apr 22;31(8):1263-1277.
Sander CL, Luu J, Kim K, Furkert D, Jang K, Reichenwallner J, Kang M, Lee HJ, Eger BT, Choe HW, Fiedler D, Ernst OP, Kim YJ, Palczewski K, Kiser PD#. Structural evidence for visual arrestin priming via complexation of phosphoinositols. Structure. 2022 Feb 3;30(2):263-277.e5.
#Corresponding
Sander, C. L., Sears, A. E., Pinto, A. F. M., Choi, E. H., Kahremany, S., Gao, F., Salom, D., Jin, H., Pardon, E., Suh, S., Dong, Z., Steyaert, J., Saghatelian, A., Skowronska-Krawczyk, D.#, Kiser, P. D.#, and Palczewski, K.# (2021) Nano-scale resolution of native retinal rod disk membranes reveals differences in lipid composition. J. Cell Biol. 220
#Co-corresponding
Choi, E. H., Suh, S., Einstein, D. E., Leinonen, H., Dong, Z., Rao, S. R., Fliesler, S. J., Blackshaw, S., Yu, M., Peachey, N. S., Palczewski, K., and Kiser, P. D.# (2021) An inducible Cre mouse for studying roles of the RPE in retinal physiology and disease. JCI Insight 6
#Corresponding
Blum, E., Zhang, J., Zaluski, J., Einstein, D. E., Korshin, E., Kubas, A., Gruzman, A.#, Tochtrop, G. P.#, Kiser, P. D.#, and Palczewski, K.# (2021) Rational alteration of pharmacokinetics of chiral fluorinated and deuterated derivatives of emixustat for retina therapies. J. Med. Chem. 64, 8287-8302
#Co-corresponding
York, N. J., Lockart, M. M., Sardar, S., Khadka, N., Shi, W., Stenkamp, R. E., Zhang, J., Kiser, P. D.#, and Pierce, B. S.# (2021) Structure of 3-mercaptopropionic acid dioxygenase with a substrate analog reveals bidentate substrate binding at the iron center. J. Biol. Chem. 100492
#Co-corresponding
Kolesnikov, A. V., Kiser, P. D., Palczewski, K., and Kefalov, V. J. (2021) Function of mammalian M-cones depends on the level of CRALBP in Muller cells. J. Gen. Physiol. 153
Kiser, P.D., and Palczewski, K. (2021) Pathways and disease-causing alterations in visual chromophore production for vertebrate vision. J. Biol. Chem. 296
Daruwalla, A., Zhang, J., Lee, H. J., Khadka, N., Farquhar, E. R., Shi, W., von Lintig, J., and Kiser, P. D.# (2020) Structural basis for carotenoid cleavage by an archaeal carotenoid dioxygenase. Proc Natl Acad Sci U S A 117, 19914-19925
#Corresponding
Suh, S., Choi, E. H., Leinonen, H., Foik, A. T., Newby, G. A., Yeh, W. H., Dong, Z., Kiser, P. D., Lyon, D. C., Liu, D. R., and Palczewski, K. (2020) Restoration of visual function in adult mice with an inherited retinal disease via adenine base editing. Nat Biomed Eng 5, 169-178
Gazda, M. A., Toomey, M. B., Araujo, P. M., Lopes, R. J., Afonso, S., Myers, C. A., Serres, K., Kiser, P. D., Hill, G. E., Corbo, J. C., and Carneiro, M. (2020) Genetic Basis of De Novo Appearance of Carotenoid Ornamentation in Bare-Parts of Canaries. Mol. Biol. Evol. 37, 1317-1328
Kiser, P.D. (2019) Alkene-cleaving carotenoid cleavage dioxygenases. in Encyclopedia of Inorganic and Bioinorganic Chemistry (Scott, R. A. ed.), John Wiley & Sons, Ltd. 1-13
Kiser, P. D.#, Kolesnikov, A. V., Kiser, J. Z., Dong, Z., Chaurasia, B., Wang, L., Summers, S. A., Hoang, T., Blackshaw, S., Peachey, N. S., Kefalov, V. J., and Palczewski, K. (2019) Conditional deletion of Des1 in the mouse retina does not impair the visual cycle in cones. FASEB J. 33, fj201802493R
#Corresponding
Khadka, N., Farquhar, E. R., Hill, H. E., Shi, W., von Lintig, J., and Kiser, P. D.# (2019) Evidence for distinct rate-limiting steps in the cleavage of alkenes by carotenoid cleavage dioxygenases. J. Biol. Chem. 294, 10596-10606
#Corresponding
Sui, X., Farquhar, E. R., Hill, H. E., von Lintig, J., Shi, W., and Kiser, P. D.#(2018) Preparation and characterization of metal-substituted carotenoid cleavage oxygenases. Journal of Biological Inorganic Chemistry 23, 887-901
#Corresponding
Choi, E. H., Suh, S., Sander, C. L., Hernandez, C. J. O., Bulman, E. R., Khadka, N., Dong, Z., Shi, W., Palczewski, K.#, and Kiser, P. D.# (2018) Insights into the pathogenesis of dominant retinitis pigmentosa associated with a D477G mutation in RPE65. Human Molecular Genetics 27, 2225-2243
#Co-corresponding
Kiser, P. D.#, Zhang, J., Sharma, A., Angueyra, J. M., Kolesnikov, A. V., Badiee, M., Tochtrop, G. P., Kinoshita, J., Peachey, N. S., Li, W., Kefalov, V. J.#, and Palczewski, K.# (2018) Retinoid isomerase inhibitors impair but do not block mammalian cone photoreceptor function. Journal of General Physiology 150, 571-590
#Co-corresponding
Sui, X., Weitz, A. C., Farquhar, E. R., Badiee, M., Banerjee, S., von Lintig, J., Tochtrop, G. P., Palczewski, K., Hendrich, M. P.#, and Kiser, P. D.# (2017) Structure and Spectroscopy of Alkene-Cleaving Dioxygenases Containing an Atypically Coordinated Non-Heme Iron Center. Biochemistry 56, 2836-2852
#Co-corresponding
Kiser, P. D., Zhang, J., Badiee, M., Kinoshita, J., Peachey, N. S., Tochtrop, G. P., and Palczewski, K. (2017) Rational Tuning of Visual Cycle Modulator Pharmacodynamics. Journal of Pharmacology and Experimental Therapeutics 362, 131-145
Sui, X., Zhang, J., Golczak, M., Palczewski, K., and Kiser, P. D. (2016) Key Residues for Catalytic Function and Metal Coordination in a Carotenoid Cleavage Dioxygenase. Journal of Biological Chemistry 291, 19401-19412
Kiser, P. D., Zhang, J., Badiee, M., Li, Q., Shi, W., Sui, X., Golczak, M., Tochtrop, G. P., and Palczewski, K. (2015) Catalytic mechanism of a retinoid isomerase essential for vertebrate vision. Nature Chemical Biology 11, 409-415
Grants
I02 BX004939-01 4/1/2024 – 3/31/2028 Department of Veterans Affairs Title: Modulation of retinoid reactivity and pathological signaling in retinal therapeutics Role: PI
NSF-2107713 9/1/2021 – 8/31/2024 National Science Foundation Title: Unraveling the principles of catalytic diversity in the carotenoid oxygenase superfamily Role: PI
R01EY034519 3/1/2023 – 2/28/2027 National Eye Institute Title: Chemical Biology of the Vertebrate Visual Pigments Role: PI
Professional Societies
The Association for Research in Vision and Ophthalmology
International Carotenoid Society
Other Experience
Research Health Scientist
VA Long Beach Healthcare System 2015—pres
Staff Pharmacist
Pharmacy Systems Inc. 2014—2018
Staff Pharmacist
CVS Pharmacy 2005—2008
Registered Pharmacist, State of California
2022—pres
Registered Pharmacist, State of Ohio
2005—pres
Graduate Programs
Cellular and Molecular Biosciences
Interdepartmental Neuroscience Program
Research Centers
Center for Translational Vision Research
Last updated
11/08/2024