Helen Willsey, PhD
Assistant Professor
Psychiatry
School of Medicine

We use Xenopus and human cell culture models to identify points of convergence among seemingly unrelated genetic risk factors, revealing common molecular mechanisms that contribute not only to autism but also to its comorbidities, including congenital heart disease and gastrointestinal dysfunction. Our approach integrates high-throughput functional genomics, live imaging, and in vivo perturbation to map the developmental trajectories altered by neurodevelopmental risk genes. By resolving the complexity introduced by genetic pleiotropy, we aim to define actionable entry points for therapeutic discovery. We're passionate about advancing both fundamental neuroscience and translational insight, while also mentoring the next generation of scientists. If you’re interested in collaboration, mentorship, or learning more about our work, feel free to connect.

• Autism gene variants disrupt enteric neuron migration and cause gastrointestinal dysmotility.
  bioRxiv : the preprint server for biology 2024 McCluskey KE, Stovell KM, Law K, Kostyanovskaya E, Schmidt J, Exner CRT, Dea J, Brimble E, State MW, Willsey AJ, Willsey HR
• Modelling human genetic disorders in Xenopus tropicalis.
  Disease models & mechanisms 2024 Willsey HR, Seaby EG, Godwin A, Ennis S, Guille M, Grainger RM
• 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