STANTON LAB
TECHNOLOGY TOWARDS TREATMENTS
Research Areas
Driven by the need for better treatments for neurological disease, we combine neurogenetics, omics, and cell biology techniques with tools spanning nanotechnology, microfluidics, microphysiological systems, biomaterials engineering, and tissue engineered organoid approaches. Below are major focal areas.
Functional Consequences of Genetic Variants
A critical bottleneck to translating genetic variant discovery into therapeutic strategies is understanding the functional consequences of the variant. As many risk variants reside in non-coding and regulatory regions not well-conserved in other animals, human cell-based systems provide unique advantages for decoding variant effects. We develop variant-specific models to probe phenotypes on both a cell type-specific basis and the tissue scale, resultant from multicellular crosstalk. Leveraging engineering techniques, we advance the biomimicry of these systems, modeling new facets of disease etiology towards increasing predictive power and translational relevance.
Drug Delivery
to the Brain
One of the most formidable challenges in developing effective neurotherapeutics is successfully delivering treatments to the brain--an organ well-protected by tightly regulated brain barriers, including the blood-brain barrier (BBB). Estimates suggest that over 98% of all small molecule drugs and almost all large molecules fail to cross the adult human BBB. To address this, we are engineering carriers for enhanced delivery, developing targeted delivery strategies, and establishing advanced systems aimed at gaining fundamental understanding and more efficiently identifying effective compounds.
Towards A Pipeline for Precision Medicine
Many neurological diseases involve a spectrum of disorders with overlapping characteristics, frequently caused by a combination of genetic variants and environmental factors. We have a strong interest in subtyping neurological disease to address underlying mechanisms on a patient-specific basis. We further aim to understand how disparate variants converge in shared pathologies and identify contributors to sporadic disease. To address this we design tools to understand underlying mechanisms and test treatments, with a view to develop precise medicines based on individuals' unique disease profiles.
Publications
For the most up-to-date list, please visit pubmed.
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Stanton AE, Bubnys A, Agbas E, James B, Park DS, Jiang A, Pinals RL, Truong N, Loon A, Staab C, Liu L, Cerit O, Wen HL, Kellis M, Blanchard JW, Langer R, and Tsai LH (2024). Engineered 3D Immuno-Glial-Neurovascular Human miBrain Model. bioRxiv. https://www.biorxiv.org/content/10.1101/2023.08.15.553453v2.
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Cable J, Arlotta P, Parker KK, Hughes AJ, Goodwin K, Mummery CL, Kamm RD, Engle SJ, Tagle DA, Boj SF, Stanton AE, et al. (2022). Engineering multicellular living systems—A Keystone Symposia report. Annals of the New York Academy of Sciences. https://nyaspubs.onlinelibrary.wiley.com/doi/abs/10.1111/nyas.14896.
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Stanton AE, Tong X, Jing SL, Behn A, Storaci H, and Yang F (2022). Aligned gelatin microribbon scaffolds with hydroxyapatite gradient for engineering the bone-tendon interface. Tissue Engineering Part A. 28:15-16, 712-723. https://www.liebertpub.com/doi/abs/10.1089/ten.TEA.2021.0099.
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Stanton AE, JP Gleghorn, AL Pavlovich, and CM Nelson (2022). Negative transmural pressure disrupts airway morphogenesis by suppressing FGF10. Frontiers in Developmental Biology. https://www.frontiersin.org/articles/10.3389/fcell.2021.725785/full.
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Stanton AE, Tong X, and Yang F (2019). Varying Solvent Type Modulates Collagen Coating and Stem Cell Mechanotransduction on Hydrogel Substrates. APL Bioengineering, 3 (3). https://pubs.aip.org/aip/apb/article/3/3/036108/22960.
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Stanton AE, Tong X, and Yang F (2019). Extracellular Matrix Type Modulates Mechanotransduction of Stem Cells, Acta Biomaterialia, 96, 310-320. https://www.sciencedirect.com/science/article/abs/pii/S1742706119304702.
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Stanton AE, Tong X, Lee S, and Yang F (2019). Biochemical Ligand Density Regulates Yes-Associated Protein Translocation in Stem Cells through Cytoskeletal Tension and Integrins. ACS Applied Materials & Interfaces, 11 (9) 8849-8857. https://pubs.acs.org/doi/abs/10.1021/acsami.8b21270.
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Lee S, Stanton AE, Tong X, and Yang F (2019). Hydrogels with enhanced protein conjugation efficiency reveal stiffness-induced YAP localization in stem cells depends on biochemical cues. Biomaterials, 202, 26-34. https://www.sciencedirect.com/science/article/abs/pii/S0142961219301188.