Speaker Bio
Dr. Sheridan has over 20 years of research experience focused on the large-scale generation, expansion, characterization and differentiation of pluripotent and multipotent stem cells and their application in basic research, disease modeling and drug discovery. As a Principal Investigator and Director of the Platform for Cellular Modeling in Neuropsychiatric Disease at Massachusetts General Hospital and Lecturer in the Dept. of Psychiatry at Harvard Medical School, his efforts have been focused on understanding neurodevelopmental and psychiatric disorders through the scaled derivation and characterization of human induced pluripotent stem cells (iPSCs), iPSC-derived neural stem/progenitor cells, differentiated neurons, microglia and astrocytes from patients of various disease backgrounds to facilitate the study of disease mechanisms and screening of potential therapeutics using cell-based assays.
He has successfully established protocols and procedures to generate large bioreactor-scale quantities of neural stem/progenitor populations, differentiated neurons, astrocytes, and microglia from human iPSC lines in genetically engineered and disease backgrounds, which has made possible large-scale phenotypic and functional characterization studies as well as the development of robust assays amenable to high-throughput screening.
He received his Ph.D. in Molecular Genetics at the University of California, Irvine and followed up with a post-doctoral fellowship in genetic engineering at Harvard University.
ICPR 2024 Abstract
Characterization of microglial functional and phenotypic modulation upon psychedelic treatment using human in vitro cellular models
Theoretical Background and Rationale: Psychedelics have been suggested to promote neuroplasticity through structural and functional changes. Understanding their impact on microglia, the immune cells of the CNS involved in synaptic plasticity through synaptic pruning, neural elimination, and neuroprotection, can provide additional non-neuronal insights into the mechanisms through which these substances may promote changes. Thus, investigating how psychedelics modulate microglial biology can help elucidate the functional bases of their therapeutic effects. Additionally, microglia may respond to psychedelics through alternative pathways than those more understood in neurons. Understanding these effects on microglia may lead to the development of novel therapeutic approaches.
Research Question and Hypothesis: Psychedelics modulate microglial phenotype and function, leading to alterations in neuroimmune responses including altering neuroinflammation and synaptic plasticity, resulting in modified neural connectivity
Methods and Analysis: We have developed methods to understand the functional and phenotypic effects of psychedelic treatments in-vitro using human induced pluripotent stem cell (iPSC)-derived microglia. By performing high-content image-based analyses, we have measured microglial functions including synaptic engulfment, morphology, motility, and other indications of activation state upon psychedelic treatment.
Main Findings: Using an array of psychedelic treatments in our in-vitro human iPSC-derived microglia cellular models, we found phenotypic and functional alterations specific to treatment on parameters of microglia function
Conclusion: While most prior work focuses on their neuronal effects, studying the effects of psychedelic treatments on microglia is valuable for understanding the neurobiological mechanisms underlying their therapeutic potential and potentially paving the way for innovative therapies for neurodevelopmental and psychiatric disorders.