Professor of Ophthalmology and Visual Sciences, Adjunct Professor of Neurobiology, and Adjunct Professor of Biological Sciences
Rod and cone photoreceptor cells in the retina mediate vision. These cells have evolved into highly polarized structures consisting of three distinct areas: the outer segment containing membrane disks housing proteins involved in phototransduction, the inner segment where biosynthesis occurs, and the synaptic terminal that transmits excitation by light to downstream neurons. The inner segment (cell body) connects to an outer segment through a narrow 9+0 transition zone and to the synaptic terminal by a slender axon.
My laboratory explores mechanisms in membrane protein transport in photoreceptors through the transition zone, a homolog of the transition zone in primary cilia. A central question concerns biogenesis and maintenance of the basal body/axoneme cytoskeleton providing the backbone for the outer segment. Defects in basal body docking to the cortex of the inner segment, extension of a transition zone and formation of the axoneme cause a number of non-syndromic and syndromic retinal disorders. Non-syndromic diseases (retinitis pigmentosa, Leber congenital amaurosis) affect only the retina. Syndromes (e.g., Bardet-Biedl, Senior Loken, and Joubert syndrome) affect multiple organs. We are generating knockout and other transgenic mouse models to mimic human retina disease phenotypes and understand mechanisms leading to disease. Finally, we are exploring gene-based and drug-based therapies to rescue the degeneration in our mouse models.
References (Selected Publications, since 2011)
- Zhang H, Constantine R, …Jorgensen EM, Hill CP, Tong L, and Baehr W (2011) UNC119 regulates G protein trafficking in sensory neurons. Nat Neurosci 14, 874-880.
- Jiang L, Zhang H, …., Frederick JM, Baehr W (2011). Long-term RNA interference gene therapy in a dominant retinitis pigmentosa mouse model. Proc Natl Acad Sci USA 108, 18476-81.
- Ying G, Avasthi P, ….. Baehr W (2014). Centrin 2 is required for mouse olfactory ciliary trafficking and development of ependymal cilia planar polarity. J Neurosci 34, 6377–6388.
- Li B, Vachali PP, …., Baehr W, Bernstein PS (2014). Inactivity of human β,β-carotene-9’,10’-dioxygenase (BCO2) underlies retinal accumulation of the human macular pigment. Proc Natl Acad Sci USA 111, 10173-10178.
- Baehr W (2015). Membrane protein trafficking in photoreceptors: The function of PDEδ. The Proctor lecture. Invest Ophthalmol Vis Sci 55, 8653-66.
- Jiang L, Wei Y, ….Frederick JM, Baehr W. (2015). Heterotrimeric Kinesin-2 (KIF3) mediates transition zone and axoneme formation of mouse photoreceptors. J Biol Chem, 15;290(20):12765-78.
- Hanke-Gogokhia C, Wu Z, … Zhang H, Baehr W (2016). Arf-like Protein 3 (ARL3) Regulates Protein Trafficking and Ciliogenesis in Mouse Photoreceptors. J Biol Chem, 291, 7142-7155. PMID: 26814127.
- Ying G, Gerstner CD, …. Baehr W (2016). Small GTPases Rab8, Rab10 and Rab11 are Dispensable for Rhodopsin Trafficking in Mouse Photoreceptors. Published 16 Aug 2016 PLOS ONE http://dx.doi.org/10.1371/journal.pone.0161236.
- Ronquillo CC, Hanke-Gogokhia C, …. Baehr W (2016). Ciliopathy-associated IQCB1/NPHP5 protein is required for mouse photoreceptor outer segment formation. FASEB J. 30(10):3400-3412. PMID: 27328943. DOI: 10.1096/fj.201600511R.
- Hanke-Gogokhia C, Wu Z, ..... Baehr W (2017). The guanine nucleotide exchange factor, Arf-like protein 13b, is essential for assembly of the mouse photoreceptor transition zone and outer segment. J Biol Chem, Dec 29;292(52):21442-21456. PMID: 29089384.
- Hanke-Gogokhia C, …. Frederick JM, Baehr W (2018). Rescue of cone function in cone-only Nphp5 knockout mouse model with Leber congenital amaurosis phenotype. Molecular Vision 24:834-846.
- Ying G, …., Frederick JM and Baehr W (2018). The small GTPase Rab28 is essential for mouse cone outer segment disc shedding. J Biol Chem 293 (45) 17546-17558.
- Baehr W, Hanke-Gogokhia C…. Ying G (2019). Insights into Photoreceptor Ciliogenesis Revealed by Animal Models. Progr. Ret Eye Res, 71, 26-56. doi: 10.1016/j.preteyeres.2018.12.004. [Epub ahead of print] Review.
- Ying G, Frederick JM and Baehr W (2019). Deletion of both centrin 2 (CETN2) and CETN3 destabilizes the distal connecting cilium of mouse photoreceptors. J Biol Chem, J Biol Chem. 294(11):3957-3973.
- Frederick JM, Hanke-Gogokhia C, Ying G and Baehr W (2019). Diffuse or hitch a ride: how photoreceptor lipidated proteins get from here to there, Biol. Chem. (de Gruyter). Dec 24. pii: /j/bchm.ahead-of-print/hsz-2019-0375/hsz-2019-0375.xml. doi: 10.1515/hsz-2019-0375. [Epub ahead of print]