Helen Willsey, PhD
Assistant Professor
Psychiatry
School of Medicine

Specifically, we created half-mutant animals (divided by the midline) by CRISPR/Cas9 targeted injections and observed defects in neural progenitor maturation for the top 10 ASD risk genes. By drug screening, we identified estrogen signaling as a potential resilience factor for multiple different genes. Going forward, we are focusing on how these risk genes affect neurogenesis, how estrogen signaling interacts, and expanding this experimental platform to begin work on other disorders with large-effect risk genes, including Schizophrenia, Tourette Disorder, ADHD, and OCD.

• A foundational atlas of autism protein interactions reveals molecular convergence.
  bioRxiv : the preprint server for biology 2024 Wang B, Vartak R, Zaltsman Y, Naing ZZC, Hennick KM, Polacco BJ, Bashir A, Eckhardt M, Bouhaddou M, Xu J, Sun N, Lasser MC, Zhou Y, McKetney J, Guiley KZ, Chan U, Kaye JA, Chadha N, Cakir M, Gordon M,…
• Autism genes converge on microtubule biology and RNA-binding proteins during excitatory neurogenesis.
  bioRxiv : the preprint server for biology 2024 Sun N, Teyssier N, Wang B, Drake S, Seyler M, Zaltsman Y, Everitt A, Teerikorpi N, Willsey HR, Goodarzi H, Tian R, Kampmann M, Willsey AJ
• Pleiotropy of autism-associated chromatin regulators.
  Development (Cambridge, England) 2023 Lasser M, Sun N, Xu Y, Wang S, Drake S, Law K, Gonzalez S, Wang B, Drury V, Castillo O, Zaltsman Y, Dea J, Bader E, McCluskey KE, State MW, Willsey AJ, Willsey HR
• Genomics, convergent neuroscience and progress in understanding autism spectrum disorder.
  Nature reviews. Neuroscience 2022 Willsey HR, Willsey AJ, Wang B, State MW
• Modeling Human Genetic Disorders with CRISPR Technologies in Xenopus.
  Cold Spring Harbor protocols 2022 Willsey HR, Guille M, Grainger RM
• Picroscope: low-cost system for simultaneous longitudinal biological imaging.
  Communications biology 2021 Ly VT, Baudin PV, Pansodtee P, Jung EA, Voitiuk K, Rosen YM, Willsey HR, Mantalas GL, Seiler ST, Selberg JA, Cordero SA, Ross JM, Rolandi M, Pollen AA, Nowakowski TJ, Haussler D, Mostajo-Radji MA, …
• Deep learning is widely applicable to phenotyping embryonic development and disease.
  Development (Cambridge, England) 2021 Naert T, Çiçek Ö, Ogar P, Bürgi M, Shaidani NI, Kaminski MM, Xu Y, Grand K, Vujanovic M, Prata D, Hildebrandt F, Brox T, Ronneberger O, Voigt FF, Helmchen F, Loffing J, Horb ME, Willsey HR, Lienkamp …
• Whole-Mount RNA In Situ Hybridization and Immunofluorescence of Xenopus Embryos and Tadpoles.
  Cold Spring Harbor protocols 2021 Willsey HR
• A convergent molecular network underlying autism and congenital heart disease.
  Cell systems 2021 Rosenthal SB, Willsey HR, Xu Y, Mei Y, Dea J, Wang S, Curtis C, Sempou E, Khokha MK, Chi NC, Willsey AJ, Fisch KM, Ideker T
• Parallel in vivo analysis of large-effect autism genes implicates cortical neurogenesis and estrogen in risk and resilience.
  Neuron 2021 Willsey HR, Exner CRT, Xu Y, Everitt A, Sun N, Wang B, Dea J, Schmunk G, Zaltsman Y, Teerikorpi N, Kim A, Anderson AS, Shin D, Seyler M, Nowakowski TJ, Harland RM, Willsey AJ, State MW
• Xenopus leads the way: Frogs as a pioneering model to understand the human brain.
  Genesis (New York, N.Y. : 2000) 2020 Exner CRT, Willsey HR
• In Xenopus ependymal cilia drive embryonic CSF circulation and brain development independently of cardiac pulsatile forces.
  Fluids and barriers of the CNS 2020 Dur AH, Tang T, Viviano S, Sekuri A, Willsey HR, Tagare HD, Kahle KT, Deniz E
• The neurodevelopmental disorder risk gene DYRK1A is required for ciliogenesis and control of brain size in Xenopus embryos.
  Development (Cambridge, England) 2020 Willsey HR, Xu Y, Everitt A, Dea J, Exner CRT, Willsey AJ, State MW, Harland RM
• DYRK1A-related intellectual disability: a syndrome associated with congenital anomalies of the kidney and urinary tract.
  Genetics in medicine : official journal of the American College of Medical Genetics 2019 Blackburn ATM, Bekheirnia N, Uma VC, Corkins ME, Xu Y, Rosenfeld JA, Bainbridge MN, Yang Y, Liu P, Madan-Khetarpal S, Delgado MR, Hudgins L, Krantz I, Rodriguez-Buritica D, Wheeler PG, Al-Gazali L, …
• Katanin-like protein Katnal2 is required for ciliogenesis and brain development in Xenopus embryos.
  Developmental biology 2018 Willsey HR, Walentek P, Exner CRT, Xu Y, Lane AB, Harland RM, Heald R, Santama N
• The Psychiatric Cell Map Initiative: A Convergent Systems Biological Approach to Illuminating Key Molecular Pathways in Neuropsychiatric Disorders.
  Cell 2018 Willsey AJ, Morris MT, Wang S, Willsey HR, Sun N, Teerikorpi N, Baum TB, Cagney G, Bender KJ, Desai TA, Srivastava D, Davis GW, Doudna J, Chang E, Sohal V, Lowenstein DH, Li H, Agard D, Keiser MJ, …
• Localized JNK signaling regulates organ size during development.
  eLife 2016 Willsey HR, Zheng X, Carlos Pastor-Pareja J, Willsey AJ, Beachy PA, Xu T
• Gp93, the Drosophila GRP94 ortholog, is required for gut epithelial homeostasis and nutrient assimilation-coupled growth control.
  Developmental biology 2010 Maynard JC, Pham T, Zheng T, Jockheck-Clark A, Rankin HB, Newgard CB, Spana EP, Nicchitta CV