Seth Blackshaw, Ph.D.

Headshot of Seth Blackshaw
  • Professor of Neuroscience

Expertise

Neurodevelopmental Disorders, Neurogenetics, Obesity ...read more

Research Interests

Regulation of hypothalamic cell fate specification and function; 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 ...read more

Background

Dr. Seth Blackshaw is a professor of neuroscience, neurology and ophthalmology at the Johns Hopkins University School of Medicine. Additionally, he serves as an investigator in both the High Throughput Biology Center and the Institute for Cell Engineering at Johns Hopkins.

His work examines the molecular basis of neuronal and glial cell fate specification and survival.  His research focuses on characterizing the network of genes that control specification of different cell types within the retina and hypothalamus, two structures that arise from the embryonic forebrain.  The ultimate goal is to use insights gained from learning how individual cell types are specified to understand how these cells contribute to the regulation of behavior, and how they can be replaced in neurodegenerative disease.

Dr. Blackshaw received a B.A. in biology and an M.S. in biochemistry from the University of Chicago in 1991. He completed his Ph.D. in neurosciences at Johns Hopkins in 1997 and subsequently conducted postdoctoral work in genetics at the Harvard University Medical School. He joined the Hopkins faculty in 2004.

Dr. Blackshaw has authored or co-authored more than 190 peer-reviewed publications and holds several patents and copyrights. His work has garnered numerous grants and awards, including the W. M. Keck Foundation Distinguished Young Scholar in Medical Research Award, the Klingenstein Fellowship, the Basil O’Connor Starter Scholar Award, the Ruth and Milton Steinbach Fund Award for Research in Macular Degeneration, and the Stein Innovation Award from Research to Prevent Blindness. He is a member of the Society for Developmental Biology and the Society for Neuroscience, and serves on the editorial boards of Biomolecules and Frontiers of Systems Biology.

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Titles

  • Professor of Neuroscience
  • Joint Appointment in Ophthalmology

Departments / Divisions

Centers & Institutes

Education

Degrees

  • Ph.D.; Johns Hopkins University School of Medicine (Maryland) (1997)

Additional Training

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

Research & Publications

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.

Lab

Lab Website: Seth Blackshaw Lab

Selected Publications

View all on PubMed

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

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

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

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

Contact for Research Inquiries

Email me Phone: 443-287-5609

Academic Affiliations & Courses

Graduate Program Affiliation

Activities & Honors

Honors

  • Basil O’Connor Starter Scholar Award, March of Dimes, 2006
  • Ruth and Milton Steinbach Fund Award for Research in Macular Degeneration, 2007
  • Young Investigator Award, National Alliance for Research on Schizophrenia and Depression , 2007
  • Distinguished Young Scholar in Medical Research Award, W. M. Keck Foundation , 2006
  • Award in the Neurosciences, Klingenstein Foundation , 2006
  • Research Grant, Whitehall Foundation , 2005
  • Research Fellowship, Sloan Foundation , 2005
  • Fellow of the Life Sciences Research Foundation, Howard Hughes Medical Institute , 1999
  • Predoctoral Fellow, Howard Hughes Medical Institute , 1991
  • , Phi Beta Kappa, 1991
  • National Merit Scholar Award, 1987
  • Summer Program Award, Telluride Association , 1986
  • Stein Innovation Award, Research to Prevent Blindness, 2019 - 2021

Memberships

  • Society for Developmental Biology
  • Society for Neuroscience

Professional Activities

  • Editorial Board, Biomolecules, 2011
  • Editorial Board, Frontiers of Systems Biology, 2011
  • Guest Editor, PNAS, 2011
  • Guest Editor, PLoS Genetics, 2011
  • Reviewing Editor - eLife, 2023

Videos & Media

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)

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