Staff Collaborate Conference Room

Brian A. Link, PhD

Brian-Link

Brian A. Link, PhD

Professor

Locations

  • Cell Biology, Neurobiology & Anatomy

Contact Information

Biography

Education

PhD, Oregon Health & Sciences University, 1997
Postdoctoral Fellow, Harvard University, 2001
BS, University of California, San Diego, CA, 1991

Research Interests

 
Cell biology of signaling during development and disease

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.

Figure 1

link_fig_2

Movie 1. In vivo confocal time-lapse movie shows heterogeneity of interkinetic nuclear migration in retinal progenitors from 24 hpf.

Mechanisms of vertebrate retinogenesis

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).

Complex gene interactions underlying glaucoma-phenotypes

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)

Brian Link, PhD

Publications

Link Lab

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