Primary cilia are conserved microtubule-based "cellular antennae" that exhibit diverse morphologies and molecular composition across cell types. Following their discovery in the mid-19th century, primary cilia have been largely dismissed by researchers as “vestigial” cellular appendages until the early 2000s, when it was discovered that they mediate transduction of all key signaling pathways in development. Due to essential roles of primary cilia in signal transduction and their nearly ubiquitous presence on human cells, defects in cilia function cause genetic disorders called ciliopathies that affect many organ systems including the brain.

 

Our lab's current research directions are highlighted below:

 

 1. How does non-canonical Galpha protein signaling modulate cilia morphology and function?

​​Defective function of heterotrimeric G (alpha/beta/gamma) proteins, which are canonically activated by G-protein-coupled receptors (GPCRs), alters cilia morphology and is associated with neurodevelopmental disorders. However, the mechanisms, by which G proteins shape cilia morphology, and the extent to which disruption of ciliary Galpha signaling contributes to anatomical and behavioral changes in neurodevelopmental disorders remain largely unknown.

 

We recently demonstrated that the non-canonical activator and chaperone of Galpha proteins RIC-8 is required for cilia membrane expansion in specialized olfactory neurons in C. elegans - a novel function for this highly conserved protein (Campagna et al., 2023 PLoS Genetics).

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​In collaboration with the O'Donnell lab, we also discovered that although RIC-8 does not regulate cilia assembly in another class of chemosensory ASH neurons, it modulates ASH cilia-mediated sensory responses (Campagna et al., bioRxiv 2026).

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2. What are the developmental mechanisms that operate in neurons to assemble primary cilia?

​Cilia deficits are increasingly reported in neurological diseases that include neurodevelopmental, psychiatric, and neurodegenerative disorders that are not recognized ciliopathies. Notably, nearly 40 percent of individuals with neurodevelopmental ciliopathies are estimated to be without a genetic diagnosis, suggesting the existence of new pathways and cilia-dependent mechanisms in brain development. This project uses bioinformatics and proteomics, to identify new conserved genes and pathways in neuronal cilia assembly and function. ​

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​We also use C. elegans as an in vivo platform for investigating the molecular basis of human neurodevelopmental disorders.  Mutations in the human GNAI1 gene that encodes the Galpha subunit of heterotrimeric G proteins cause severe neurodevelopmental disorder associated with developmental delay, seizures, and autistic features. We discovered that GNAI1 is necessary for building primary cilia in human cells and used C. elegans as a whole-animal model to functionally classify a subset of patient mutations (Salama et al., 2025).

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3. What are the mechanisms and functional outcomes of stress-dependent cilia remodeling?

After exposure to environmental stress, primary cilia undergo structural remodeling, which is associated with altered cellular signaling output. These observations come largely from in vitro studies and make it clear that ciliary response to stress is dependent on stressor and cell context. However, the mechanisms or functional consequences of stress-dependent cilia remodeling in vivo remain largely unknown. We use C. elegans as a model to investigate cellular and molecular mechanisms that mediate stress-dependent cilia remodeling and signaling outcomes across neuron classes and stressors.

  

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