Seth Blackshaw, PhD

Primary Academic Title

Professor of Neuroscience

Background

Centers and Institutes

• Basic Biomedical Sciences, Institute for
• Cell Engineering, Institute for

Videos

• Dr. Seth Blackshaw | Neurons That Control Biological Rhythms and Sleep

Recent News Articles and Media Coverage

• Proof-of-Concept Study Advances Potential New Way to Deliver Gene Therapy, Johns Hopkins Medicine (October 27, 2022)

  Finding a cell's true identity, Eurekalert (May 28, 2019)

  Love your beauty rest? You can thank these brain cells, ScienceDaily (August 31, 2017)

  Sleep Cycles Explained—No Jet Lag When Running a Fever, R&D World (December 27, 2016)

  Researchers Pinpoint Protein Crucial For Development Of Biological Rhythms In Mice, Johns Hopkins Medicine (April 24, 2014)

  Neural Protective Protein Has Two Faces, Johns Hopkins Medicine  (May 29, 2012)

  Weight Struggles? Blame New Neurons in Your Hypothalamus, Johns Hopkins Medicine (May 21, 2012)

  Genetic ''Parts'' List Now Available For Key Part of The Mammalian Brain, Johns Hopkins Medicine (June 3, 2010)

  'Moonlighting' Molecules Discovered, Johns Hopkins Medicine (October 29, 2009)

  The Difference Between Eye Cells is...Sumo?, Johns Hopkins Medicine (March 9, 2009)

Additional Academic Titles

Joint Appointment in Ophthalmology

Contact for Research Inquiries

Phone: (443) 287-5609
sblack@jhmi.edu

Research Interests

Functional analysis of candidate regulators of cell specification and survival in retina, High throughput screening, Molecular basis of neuronal and glial cell fate specification and survival, Regulation of hypothalamic cell fate specification and function

Lab Website

Seth Blackshaw Lab - Lab Website

• The Seth Blackshaw Lab uses functional genomics and proteomics to rapidly identify the molecular mechanisms that regulate cell specification and survival in both the retina and hypothalamus. We have profiled gene expression in both these tissues, from the start to the end of neurogenesis, characterizing the cellular expression patterns of more than 1,800 differentially expressed transcripts in both tissues. Working together with the lab of Heng Zhu in the Department of Pharmacology, we have also generated a protein microarray comprised of nearly 20,000 unique full-length human proteins, which we use to identify biochemical targets of developmentally important genes of interest.

Research Summary

The vertebrate central nervous system (CNS) is an amazingly complex structure composed of distinct subtypes of neurons and glia.  To identify the molecular mechanisms that regulate cell specification in the CNS, we use the mouse retina and hypothalamus, both of which arise from the ventral embryonic forebrain.  The relatively simple anatomy of the retina provides an excellent system to identify molecular mechanisms that regulate neuronal cell fate.  The hypothalamus, which is a central regulator of behaviors ranging from sleep to feeding to reproduction, offers an opportunity to bring the power of developmental genetics to help unravel the neural circuitry controlling a huge range of experimentally tractable and medically important behaviors.

In recent years, we have worked to map out the transcriptional regulatory networks controlling the developmental competence of retinal progenitor cells, photoreceptor specification and survival, as well how retinal glia are specified and help promote photoreceptor survival.  In the hypothalamus, we have identified transcription factors that are essential for specification of neural circuitry controlling circadian rhythms and sleep.  We also discovered that tanycytes of the hypothalamic median eminence are a diet-responsive neural progenitor cell population.  Future work will investigate the function of novel candidate regulators of retinal and hypothalamic cell identity, the role of previously uncharacterized hypothalamic cell subtypes in regulating motivated behaviors, and the contribution of tanycyte-derived neurogenesis to the regulation of feeding and body weight.

PubMed

http://www.ncbi.nlm.nih.gov/pubmed?term=Blackshaw%20s

Selected Publications

• Clark BS, Stein-O’Brien GL, Shiau F, Cannon GH, Davis E, Sherman T, Rajaii F, James-Esposito RE, Gronostajski RM, Fertig EJ, Goff LA, and Blackshaw S.   Comprehensive analysis of retinal development at single cell resolution identifies NFI factors as essential for mitotic exit and specification of late-born cells.  Neuron 2019 102:1111-1126

• Hoang T, Wang J, Boyd P, Wang F, Santiago C, Jiang L, Lahne M, Todd LJ, Saez C, Yoo S, Keuthan C, Palazzo I, Squires N, Campbell WA , Jia M, Rajaii F, Payail T, Wang G , Ash J, Fischer AJ, Hyde DR, Qian J, and Blackshaw S. Cross-species transcriptomic and epigenomic analysis reveals key regulators of injury response and neuronal regeneration in vertebrate retinas.  Science 2020 3706519:eabb8598

• Liu K, Kim J, Kim DW, Zhang S, Denaxa M, Bao H, Lim SA, Kim E, Liu C, Wickersham IR, Pachinis V, Hattar S, Song J, Brown SR, and Blackshaw S. Lhx6-positive GABAergic neurons of the zona incerta promote sleep.  Nature 2017 548:582-587

• YLing J, Bygrave A, Santiago CP, Trinh V, Carmen R, Yu M, Li Y, Han J, Taneja K, Liu Y, Dongmo R, Babola T, Parker P, Jiang L, Leavey P, Smith J, Vistein R, Gimmen M, Dubner B, Teodorescu P, Kanold P, Bergles D, Langmead B, Sun S, Nielsen K, Peachey N, Singh M, Dalton W, Rajaii F, Huganir R, and Blackshaw S. Cell-specific regulation of gene expression using splicing-dependent frameshifting. Nature Communications 2022 13:5773

• Yoo S,  Kim J, Lyu P, Hoang TV, Ma A, Trinh V, Dai W, Jiang L, Leavy P, Won JK, Park SH, Qian J, Brown SP, and Blackshaw S. Control of neurogenic competence in mammalian hypothalamic tanycytes. Science Advances 2021 7:eabg3777

Honors

• Stein Innovation Award, Research to Prevent Blindness, 12/1/19
• Ruth and Milton Steinbach Fund Award for Research in Macular Degeneration, 1/1/07
• Young Investigator Award, National Alliance for Research on Schizophrenia and Depression, 1/1/07
• Basil O'Connor Starter Scholar Award, March of Dimes, 1/1/06
• Distinguished Young Scholar in Medical Research Award, W. M. Keck Foundation, 1/1/06
• Award in the Neurosciences, Klingenstein Foundation, 1/1/06
• Research Grant, Whitehall Foundation, 1/1/05
• Research Fellowship, Sloan Foundation, 1/1/05
• Fellow of the Life Sciences Research Foundation, Howard Hughes Medical Institute, 1/1/99
• Predoctoral Fellow, Howard Hughes Medical Institute, 1/1/91
• National Merit Scholar Award, 1/1/87
• Summer Program Award, Telluride Association, 1/1/86

Graduate Program Affiliations

• Cellular and Molecular Medicine
• Biochemistry, Cellular and Molecular Biology 
• Human Genetics and Molecular Biology
• Neuroscience

Memberships

• Society for Developmental Biology
• Society for Neuroscience

Professional Activities

• Biomolecules, Editorial Board, 1/1/11
• Frontiers of Systems Biology, Editorial Board, 1/1/11
• PLoS Genetics, Guest Editor, 1/1/11
• PNAS, Guest Editor, 1/1/11

Additional Training

Harvard University Medical School, Boston, MA, 2004, Genetics; Johns Hopkins University School of Medicine, Baltimore, MD, 1999, Neuroscience