Kassandra Ori-McKenney

Microtubules are dynamic cytoskeletal polymers that play essential roles in neuronal development, function, and plasticity. By regulating neuronal morphology, intracellular transport, and the organization and delivery of cellular components, microtubules provide a critical structural framework for changes in neuronal connectivity. Prior work has demonstrated that serotonergic psychedelics and related compounds, which are termed psychoplastogens, rapidly promote neuritogenesis, spinogenesis, and synaptogenesis through TrkB, mTOR, and 5-HT2A-dependent signaling. These findings raise the possibility that regulation of the microtubule cytoskeleton may contribute to the persistent structural changes induced by psychoplastogens. We have recently demonstrated that the microtubule cytoskeleton is a highly responsive system that integrates cellular signals and environmental changes to regulate microtubule dynamics and cellular function. We found that changes in cytoplasmic density, such as those accompanying osmotic stress, remodel the microtubule lattice and alter microtubule-associated protein (MAP) binding, which in turn differentially regulates tubulin posttranslational modifications (PTMs). These MAP-PTM combinations selectively control intracellular cargo transport, demonstrating that cells can adapt microtubule function to changing physiological conditions. We further showed that another MAP, tau, is an active regulator of microtubule dynamics whose phosphorylation increases microtubule dynamicity and, following traumatic brain injury, drives behavioral changes through activation of dopaminergic and serotonergic circuits. We then found that increases in the tubulin PTM, acetylation, is a conserved feature of cellular senescence and aging, and impairs microtubule polymerization, disrupts secretory vesicle transport, and alters cytoplasmic mechanics. Together, these findings establish that regulated changes in MAPs and tubulin PTMs provide a mechanism for cellular adaptation by tuning cytoskeletal dynamics and function. To determine whether psychoplastogens directly regulate this adaptive cytoskeletal system, we examined the effects of psilocin on tubulin PTMs in BEAS-2B cells. We found that psilocin selectively altered the tubulin PTM landscape, with only one of the PTM signatures examined showing a significant change. This highly selective response suggests that psychoplastogens may regulate the microtubule cytoskeleton through specific, acute remodeling of the tubulin code rather than through global changes in microtubule PTMs. Our findings identify the microtubule cytoskeleton as a potential target of psilocin and provide a new framework for investigating how psychedelic signaling may be translated into the structural changes underlying neural plasticity.

Dr. Kassandra Ori-McKenney is Professor of Molecular and Cellular Biology at the University of California, Davis. She received her B.A. cum laude in Neuroscience and Behavior from Vassar College in 2005, followed by an M.A. (2007), M.Phil. (2009), and Ph.D. with distinction (2011) in Biological Sciences from Columbia University, where she studied cytoplasmic dynein in neurodevelopmental and neurodegenerative disease under the mentorship of Richard Vallee. She subsequently completed a postdoctoral fellowship in Neurobiology at the University of California, San Francisco, under the mentorship of Yuh Nung Jan.

Dr. Ori-McKenney joined UC Davis in 2016 as an Assistant Professor and was promoted to Associate Professor in 2021 and Professor in 2026. Her honors include the Presidential Early Career Award for Scientists and Engineers (PECASE, 2025), the UC Davis Chancellor’s Fellow (2024), Pew Biomedical Scholars Award (2018), Simons Foundation Autism Research Initiative Pilot Award (2017), March of Dimes Basil O’Connor Scholar Award (2017), and NIH K99 Pathway to Independence Award (2014). She was also named a Cell Scientist to Watch by the Journal of Cell Science in 2019 and received the Jane Coffin Childs Postdoctoral Research Award in 2011.