
Brian A. Link, PhD
Professor
Locations
- Cell Biology, Neurobiology & Anatomy
Contact Information
Education
Postdoctoral Fellow, Harvard University, 2001
BS, University of California, San Diego, CA, 1991
Research Interests
The overarching research goal of the Link lab is to study the cellular basis of signaling and the role in development and relationships to disease processes. We primarily use zebrafish for our studies, combining imaging based technologies and genome editing. As part of this research we have developed tools to monitor and manipulate basic cellular processes such as endocytosis, vesicle trafficking and nuclear dynamics. In addition, we have created transgenic animals to investigate and quantitate signaling networks including Notch, BMP/Smad, and Hippo-Yap/Taz. There are several areas of research we are currently focused. One goal is to understand the cell biology and signaling events critical for ocular development and disease. Currently we are studying how endocytosis and polarized vesicle trafficking affect signaling, primarily Notch, Wnt and Hippo-Yap/Taz pathways, in neuroepithelia and how these pathways interact to regulate neurogenesis. Ancillary to these studies, we are characterizing the role of Yap/Taz activity in retinal pigment epithelial development and maintenance. For ocular disease studies, we are characterizing the cellular mechanisms underlying pathology in several eye disorders including PhR degenerations, glaucomas, and myopia. Integrated with all these research goals, the Link lab emphasizes collaborative research and career training for students and post-docs.
Movie 1. In vivo confocal time-lapse movie shows heterogeneity of interkinetic nuclear migration in retinal progenitors from 24 hpf.
Images are composed of compressed z-stacks of H2A-GFP fluorescence overlaid with single mid-plane bright-field images. Apical and basal surfaces are outlined with dashed white lines in the first and last frame and an arrow indicates a cell undergoing mitosis at the apical surface. The movie plays at 6 frames per second covering 12 hr of development time (Baye and Link, 2007).
Specifically, neuroepithelia with deep basal nuclear migrations and shorter cell cycles are biased to produce neurons, rather than give rise to daughter cells that re-enter the cell cycle. The lab is currently exploring the signals and mechanisms underlying these relationships.
Complex gene interactions underlying glaucoma-phenotypes
The overall goal of these studies is to understand the relationships between genes that contribute to glaucoma-phenotypes. The glaucomas are a heterogeneous group of ocular disorders characterized by retinal ganglion cell death, optic nerve damage and visual field loss. Elevated intraocular pressure is a principal risk factor for this neurodegenerative disease. The majority and perhaps all forms of glaucoma are complex – requiring the interaction of multiple genes. While several genes that contribute to glaucoma have been identified, many additional loci remain unknown. We are using zebrafish to identify and study genes which promote glaucoma-phenotypes (Figure 3).
In particular, we are focusing on the complex-gene interactions that promote retinal ganglion cell death in the context of elevated intraocular pressure. Additional projects are focused on genes that regulate the development of glaucoma-relevant ocular tissues, as such genes have previously been shown to impact glaucoma (Movie 2).
Movie 2. In vivo confocal time-lapse movie showing migration of neural crest cells into the periocular region of the eye. These cells, along with head mesoderm, contribute to the structures of the anterior segment that regulate intraocular pressure. Cells were labeled with the foxd3:GFP transgene (Gilmour et al. Neuron 34:577-88, 2002)
Publications
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(Brandt ZJ, Echert AE, Bostrom JR, North PN, Link BA.) Development. 2020 06 22;147(12) PMID: 32439761 PMCID: PMC7328147 SCOPUS ID: 2-s2.0-85087440712 05/23/2020
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Upstream regulation of the Hippo-Yap pathway in cardiomyocyte regeneration.
(Flinn MA, Link BA, O'Meara CC.) Semin Cell Dev Biol. 2020 04;100:11-19 PMID: 31606277 PMCID: PMC7263368 SCOPUS ID: 2-s2.0-85073003673 10/14/2019
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(Clark EM, Nonarath HJT, Bostrom JR, Link BA.) Dis Model Mech. 2020 01 28;13(1) PMID: 31852729 PMCID: PMC6994954 SCOPUS ID: 2-s2.0-85079534293 12/20/2019
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Somatic Mutations of lats2 Cause Peripheral Nerve Sheath Tumors in Zebrafish.
(Brandt ZJ, North PN, Link BA.) Cells. 2019 08 25;8(9) PMID: 31450674 PMCID: PMC6770745 SCOPUS ID: 2-s2.0-85084889096 08/28/2019
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The Roles of Hippo Signaling Transducers Yap and Taz in Chromatin Remodeling.
(Hillmer RE, Link BA.) Cells. 2019 05 24;8(5) PMID: 31137701 PMCID: PMC6562424 05/30/2019
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(Flinn MA, Jeffery BE, O'Meara CC, Link BA.) Cardiovasc Res. 2019 03 01;115(3):570-577 PMID: 30295714 SCOPUS ID: 2-s2.0-85061983162 10/09/2018
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The Hippo Pathway Regulates Caveolae Expression and Mediates Flow Response via Caveolae.
(Rausch V, Bostrom JR, Park J, Bravo IR, Feng Y, Hay DC, Link BA, Hansen CG.) Curr Biol. 2019 01 21;29(2):242-255.e6 PMID: 30595521 PMCID: PMC6345631 SCOPUS ID: 2-s2.0-85060027631 01/01/2019
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(Collery RF, Link BA.) Front Cell Dev Biol. 2019;7:167 PMID: 31457013 PMCID: PMC6700241 SCOPUS ID: 2-s2.0-85072723134 08/29/2019
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Regeneration of the zebrafish retinal pigment epithelium after widespread genetic ablation.
(Hanovice NJ, Leach LL, Slater K, Gabriel AE, Romanovicz D, Shao E, Collery R, Burton EA, Lathrop KL, Link BA, Gross JM.) PLoS Genet. 2019 01;15(1):e1007939 PMID: 30695061 PMCID: PMC6368336 SCOPUS ID: 2-s2.0-85061272556 01/30/2019
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Kif17 phosphorylation regulates photoreceptor outer segment turnover.
(Lewis TR, Kundinger SR, Link BA, Insinna C, Besharse JC.) BMC Cell Biol. 2018 11 20;19(1):25 PMID: 30458707 PMCID: PMC6245759 SCOPUS ID: 2-s2.0-85056802940 11/22/2018
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Yap regulates glucose utilization and sustains nucleotide synthesis to enable organ growth.
(Cox AG, Tsomides A, Yimlamai D, Hwang KL, Miesfeld J, Galli GG, Fowl BH, Fort M, Ma KY, Sullivan MR, Hosios AM, Snay E, Yuan M, Brown KK, Lien EC, Chhangawala S, Steinhauser ML, Asara JM, Houvras Y, Link B, Vander Heiden MG, Camargo FD, Goessling W.) EMBO J. 2018 11 15;37(22) PMID: 30348863 PMCID: PMC6236334 SCOPUS ID: 2-s2.0-85055253100 10/24/2018
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(Lapierre-Landry M, Huckenpahler AL, Link BA, Collery RF, Carroll J, Skala MC.) Transl Vis Sci Technol. 2018;7(5):4 PMID: 30197836 PMCID: PMC6126953 09/11/2018
Link Lab
