Helen Willsey
University of California-San Francisco, CA·Neuroscience·Early-career
Researchers have identified hundreds of genes that strongly raise the risk of autism spectrum disorder (ASD), but how these genes lead to autism is still poorly understood. No treatments based on the condition's biology exist.
- Fields
Neuroscience
Genetics
Biology
- Topics
autism spectrum disorder
autism genetics
primary cilia
- Grants
- 2 known grants, through Apr 2031
What they work on
- Determine how SYNGAP1 gene dosage affects cilia formation and Hedgehog signaling in human neural progenitor cells before synapses form, and how this changes their proliferation and differentiation.
- Define how SYNGAP1 domains, isoforms and GTPase intermediates regulate PKA signaling within neuronal primary cilia, and how this regulation changes as synapses mature.
- Assess how SYNGAP1 loss alters the structure and function of motile cilia using human nasal brushings and Xenopus frog models, and identify possible therapeutic entry points in this accessible tissue.
- Test whether five autism-associated chromatin regulators localize to and act at microtubule structures such as mitotic spindles, growth cones and cilia, using the Xenopus experimental toolkit.
- Profile tubulin post-translational modifications in human cells with proteomics to identify the 'tubulin code' changes through which autism-linked chromatin regulators control microtubule dynamics.
More about the research
Researchers often infer a gene's job from database labels. This has focused attention on synapses, the junctions between neurons, and on proteins that control gene activity. The lab's projects test the idea that many autism genes are pleiotropic, meaning they do several jobs in different parts of the cell. These include roles at cilia, hair-like cell projections, and at microtubules, the protein filaments that give cells structure and make up the core of cilia.
Why it matters
Autism currently has no treatments based on its biology. If autism genes act partly through cilia, airway cilia could serve as biomarkers to help diagnose and monitor ASD and as accessible treatment targets, because they can be sampled with a simple nasal brushing. Showing that chromatin regulators also control microtubules could change how autism genes are studied. It may also extend to other conditions where these genes are implicated, such as schizophrenia.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Susan Dutcher
Washington University in St Louis, MO·Genetics
Determine how microtubule inner proteins (MIPs) inside ciliary doublet microtubules produce the symmetric beating used by sperm and nodal cilia, and test whether they act through outer dynein arms and tektin. Genetic, biochemical, proteomic and imaging approaches will be used.
Tamara Caspary
Emory University, GA·Genetics
Define the ciliary cAMP signaling signature in kidney epithelial cells that express only a cilia-excluded variant of ARL13B, a small GTPase concentrated in primary cilia.
Francesca Bartolini
Columbia University, NY·Neuroscience
Test whether unrelated CIPN-causing chemotherapy drugs share a mechanism of altering tubulin post-translational modifications early, before neuropathy symptoms appear, using cellular and preclinical models.
The school
University of California-San Francisco: 89 labs on PI Pages, $2.1B a year on research, 164 research doctorates a year.
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