@article{sen_voulgaropoulos_keung_2021, title={Effects of early geometric confinement on the transcriptomic profile of human cerebral organoids}, volume={21}, ISSN={["1472-6750"]}, DOI={10.1186/s12896-021-00718-2}, abstractNote={Abstract}, number={1}, journal={BMC BIOTECHNOLOGY}, author={Sen, Dilara and Voulgaropoulos, Alexis and Keung, Albert J.}, year={2021}, month={Oct} } @article{sen_drobna_keung_2021, title={Evaluation of UBE3A antibodies in mice and human cerebral organoids}, volume={11}, ISSN={["2045-2322"]}, DOI={10.1038/s41598-021-85923-x}, abstractNote={Abstract}, number={1}, journal={SCIENTIFIC REPORTS}, author={Sen, Dilara and Drobna, Zuzana and Keung, Albert J.}, year={2021}, month={Mar} } @misc{sen_keung_2020, title={Capturing complex epigenetic phenomena through human multicellular systems}, volume={16}, ISSN={["2468-4511"]}, DOI={10.1016/j.cobme.2020.05.008}, abstractNote={Epigenetic states inherently define a wide range of complex biological phenotypes and processes in development and disease. Accurate cellular modeling would ideally capture the epigenetic complexity of these processes as well as the accompanying molecular changes in chromatin biochemistry including in DNA and histone modifications. Here we highlight recent work that demonstrate how multicellular systems provide a natural approach to capture complex epigenetic phenomena. They accomplish this through more closely matching the in vivo environment and through the intrinsic nature of multicellular systems being able to generate and model multiple distinct cellular states, all within one system. We also discuss challenges and limitations of such systems, efforts to tune and modulate epigenetics directly in multicellular systems, and how molecular interventional approaches could advance and improve the utility of these models.}, journal={CURRENT OPINION IN BIOMEDICAL ENGINEERING}, author={Sen, Dilara and Keung, Albert J.}, year={2020}, month={Dec}, pages={34–41} } @article{sen_voulgaropoulos_drobna_keung_2020, title={Human Cerebral Organoids Reveal Early Spatiotemporal Dynamics and Pharmacological Responses of UBE3A}, volume={15}, ISSN={["2213-6711"]}, DOI={10.1016/j.stemcr.2020.08.006}, abstractNote={Angelman syndrome is a complex neurodevelopmental disorder characterized by delayed development, intellectual disability, speech impairment, and ataxia. It results from the loss of UBE3A protein, an E3 ubiquitin ligase, in neurons of the brain. Despite the dynamic spatiotemporal expression of UBE3A observed in rodents and the potential clinical importance of when and where it is expressed, its expression pattern in humans remains unknown. This reflects a common challenge of studying human neurodevelopment: prenatal periods are hard to access experimentally. In this work, human cerebral organoids reveal a change from weak to strong UBE3A in neuronal nuclei within 3 weeks of culture. Angelman syndrome human induced pluripotent stem cell-derived organoids also exhibit early silencing of paternal UBE3A, with topoisomerase inhibitors partially rescuing UBE3A levels and calcium transient phenotypes. This work establishes human cerebral organoids as an important model for studying UBE3A and motivates their broader use in understanding complex neurodevelopmental disorders.}, number={4}, journal={STEM CELL REPORTS}, author={Sen, Dilara and Voulgaropoulos, Alexis and Drobna, Zuzana and Keung, Albert J.}, year={2020}, month={Oct}, pages={845–854} }