Brian Clark, Ph.D.

Assistant Professor
Ophthalmology and Visual Sciences

Developmental, Regenerative and Stem Cell Biology Program
Neurosciences Program
Molecular Genetics and Genomics Program

Research Abstract:

Using single cell RNA-sequencing techniques developing mouse and human retinas (Clark and Stein-O’Brien, et al, 2019; Neuron; Lu and Shiau, et al, 2019; bioRxiv), we are beginning to understand the transcriptional signature of retinal progenitors across development and during the process of retinal neurogenesis. We have identified numerous genes with unknown retinal function that display both dynamic and temporally restricted expression patterns that we hypothesize to be important in the regulation of retinal development. Using a suite of moderate to high-throughput genetic and molecular biology techniques, we aim to identify the mechanisms by which these genes function to control retinal neurogenesis and cell fate specification. This includes analysis of transcriptional state, epigenetics, and cis¬-regulatory sequence activity within individual cells, across retinal development.

While many of the candidate genes encode for proteins, the lab is also focused on understanding the roles of long, non-protein coding RNAs (lncRNAs) during retinal development. We are in the process of developing novel tools to study the in vivo mechanisms by which these unique biomolecules function. Combined, we anticipate these studies to expand our understanding on the mechanisms governing transcriptional regulation and cell fate specification.

Selected Publications:

Single-cell analysis of human retina identifies evolutionarily conserved and species-specific mechanisms controlling development. Lu Y, Shiau F, Yi W, Lu S, Wu Q, Pearson JD, Kallman A, Hoang T, Zhong S, Zuo Z, Zhao F, Tsai N, Zhuo Y, He S, Zhang J, Stein-O’Brien GL, Sherman TD, Duan X, Fertig EJ, Goff LA, Zack DJ, Handa JT, Xue T, Bremner R^, Blackshaw S^, Wang X^, Clark BS^. (2019) bioRxiv. https://www.biorxiv.org/content/10.1101/779694v1

Single-Cell RNA-Seq Analysis of Retinal Development Identifies NFI Factors as Regulating Mitotic Exit and Late-Born Cell Specification. Clark BS, Stein-O'Brien GL, Shiau F, Cannon GH, Davis-Marcisak E, Sherman T, Santiago CP, Hoang TV, Rajaii F, James-Esposito RE, Gronostajski RM, Fertig EJ, Goff LA, Blackshaw S. (2019) Neuron. https://www.ncbi.nlm.nih.gov/pubmed/31128945

Decomposing Cell Identity for Transfer Learning across Cellular Measurements, Platforms, Tissues, and Species. Stein-O'Brien GL*, Clark BS*, Sherman T, Zibetti C, Hu Q, Sealfon R, Liu S, Qian J, Colantuoni C, Blackshaw S, Goff LA, Fertig EJ. (2019) Cell Systems. https://www.ncbi.nlm.nih.gov/pubmed/31121116

Understanding the Role of lncRNAs in Nervous System Development. Clark BS, Blackshaw S. (2017) Adv Exp Med Biol. https://www.ncbi.nlm.nih.gov/pubmed/28815543

Long non-coding RNA-dependent transcriptional regulation in neuronal development and disease. Clark BS, Blackshaw S. (2014) Front Genet. https://www.ncbi.nlm.nih.gov/pubmed/24936207

Full list of publications available at: https://www.ncbi.nlm.nih.gov/pubmed/?term=clark%2C+brian+s

Last Updated: 11/15/2019 10:27:07 PM

UMAP dimension reduction single-cell RNA-sequencing experiments across retinal development in mouse (left) and human (right) with individual cells colored by developmental age or annotated cell type, respectively.
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