Engineering Neural Tissues
Our primary model system is human pluripotent stem cells (hPSCs) and the specialized cell types we derive from them. We harness the broad developmental potential of these cells to model tissue development in 2D cultures, as well as 3D tissue organoids and micropatterned brain tissues.
We're working to develop reproducible hPSC models that are increasingly able to mimic human microenvironments, making them incredibly powerful tools for research into the developing brain.
Knock, E., & Julian, L. M. (2021). Frontiers in cellular neuroscience, 15, 767457. https://doi.org/10.3389/fncel.2021.767457
Modifying NSC fates
To realize the developmental potential of hPSCs, we are working to understand the precise regulatory mechanisms that drive cellular development. These mechanisms involve many biochemical cascades that intersect and often synergize with each other to ultimately determine hPSC and neural stem cell (NSC) fate.
This knowledge allows us to adapt our hPSC models of the developing brain accordingly, which enables us to create new tools to answer new questions.
Allen, G. E., Dhanda, A. S., & Julian, L. M. (2022). Methods in molecular biology (Clifton, N.J.), 2515, 319–342. https://doi.org/10.1007/978-1-0716-2409-8_20
Investigating Brain Disorders
Some of the hPSC lines we work with are reprogrammed from patients who carry disease-causing genetic mutations, or have undergone genome editing to carry mutations of interest. We also employ high-throughput techniques like functional metabolic profiling, live-cell and high content imaging, and automated neural activity analysis.
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Currently, we are focused on a set of neurodevelopmental disorders called malformations of cortical development (MCD), as well as early onset neurodegenerative disorders like Spinocerebellar Ataxia and CLN3 Batten Disease.​​
Delaney, S. P., Julian, L. M., & Stanford, W. L. (2014). Frontiers in cell and developmental biology, 2, 69. https://doi.org/10.3389/fcell.2014.00069
Enabling personalized medicine
Our long-term vision is to identify regulatory mechanisms of hPSCs, particularly as they produce brain cells and tissues, that can be exploited for different purposes. These include disease modelling and drug development, tissue regeneration applications, and identifying causative biological mechanisms or biomarkers that will guide the development of next-generation therapies.
