@article{voulgaropoulos_2022, title={Mitigation of PFAS in US Public Water Systems: Future steps for ensuring safer drinking water}, ISSN={["1944-7450"]}, DOI={10.1002/ep.13800}, abstractNote={AbstractThe circulation and usage of per‐ and polyfluoroalkyl substances (PFAS) and PFAS‐derived products, such as Teflon and aqueous film‐forming foam (AFFF), have led to PFAS being found in organisms worldwide. PFAS are emerging chemical contaminants that are toxic and take a long time to break down in the environment. PFAS can cause adverse health effects, including kidney cancer, testicular cancer, and ulcerative colitis. Studies have shown a widespread presence of PFAS in public water systems and people across the United States. The main pollution sources that contribute to PFAS in water are the chemical manufacturing industry, AFFF runoff, and landfills. With the health issues associated, and the occurrence in water systems, action should be taken to reduce PFAS in drinking water. Despite the adverse health effects associated with PFAS, the Environmental Protection Agency has not yet set enforceable limits for the chemicals in drinking water. Future actions should tackle two areas: (1) reducing the contamination at the pollution source and (2) improving the quality of PFAS contaminated drinking water. Five recommendations are suggested for key stakeholders. Contamination can be reduced by setting stricter industrial controls for waste streams, phasing out AFFF usage, and banning the majority of PFAS. Drinking water quality can be improved through setting state‐enforced maximum contaminant levels and equipping water treatment plants with adequate PFAS removal technologies. Application of these recommendations could help reduce the presence of PFAS in drinking water and ensure safer drinking water for communities across the United States.}, journal={ENVIRONMENTAL PROGRESS & SUSTAINABLE ENERGY}, author={Voulgaropoulos, Alexis}, year={2022}, month={Feb} }
 @article{sen_voulgaropoulos_keung_2021, title={Effects of early geometric confinement on the transcriptomic profile of human cerebral organoids}, volume={21}, ISSN={["1472-6750"]}, url={https://doi.org/10.1186/s12896-021-00718-2}, DOI={10.1186/s12896-021-00718-2}, abstractNote={Abstract
                Background
                Human cerebral organoids (hCO) are attractive systems due to their ability to model important brain regions and transcriptomics of early in vivo brain development. To date, they have been used to understand the effects of genetics and soluble factors on neurodevelopment. Interestingly, one of the main advantages of hCOs are that they provide three dimensionality that better mimics the in vivo environment; yet, despite this central feature it remains unclear how spatial and mechanical properties regulate hCO and neurodevelopment. While biophysical factors such as shape and mechanical forces are known to play crucial roles in stem cell differentiation, embryogenesis and neurodevelopment, much of this work investigated two dimensional systems or relied on correlative observations of native developing tissues in three dimensions. Using hCOs to establish links between spatial factors and neurodevelopment will require the use of new approaches and could reveal fundamental principles of brain organogenesis as well as improve hCOs as an experimental model.
              
                Results
                Here, we investigated the effects of early geometric confinements on transcriptomic changes during hCO differentiation. Using a custom and tunable agarose microwell platform we generated embryoid bodies (EB) of diverse shapes mimicking several structures from embryogenesis and neurodevelopment and then further differentiated those EBs to whole brain hCOs. Our results showed that the microwells did not have negative gross impacts on the ability of the hCOs to differentiate towards neural fates, and there were clear shape dependent effects on neural lineage specification. In particular we observed that non-spherical shapes showed signs of altered neurodevelopmental kinetics and favored the development of medial ganglionic eminence-associated brain regions and cell types over cortical regions. Transcriptomic analysis suggests these mechanotransducive effects may be mediated by integrin and Wnt signaling.
              
                Conclusions
                The findings presented here suggest a role for spatial factors in brain region specification during hCO development. Understanding these spatial patterning factors will not only improve understanding of in vivo development and differentiation, but also provide important handles with which to advance and improve control over human model systems for in vitro applications.
              }, number={1}, journal={BMC BIOTECHNOLOGY}, author={Sen, Dilara and Voulgaropoulos, Alexis and Keung, Albert J.}, year={2021}, month={Oct} }
 @article{sen_voulgaropoulos_drobna_keung_2020, title={Human Cerebral Organoids Reveal Early Spatiotemporal Dynamics and Pharmacological Responses of UBE3A}, volume={15}, ISSN={["2213-6711"]}, url={https://doi.org/10.1016/j.stemcr.2020.08.006}, 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} }