Our research seen by one of Sergiu's patients with autism
Functional Human Brain Models of Disease
A critical challenge in understanding the intricate programs underlying development, assembly and dysfunction of the human brain is the lack of direct access to intact, functioning human brain tissue for detailed investigation by imaging, recording, and stimulation (Nature, 2018; Science, 2018).
Our lab is using pluripotent stem cells (iPS cells) derived non-invasively from individuals to generate in a dish specific regions of the human brain in a functional 3D preparation we have developed.
We are using months-to-years long ‘brain-a-dish’ cultures (also known as brain region-specific organoids or spheroids) to understand how neurons find their final position in the brain and how they mature functionally.
We are pursuing questions in at least two major inter-related areas:
First, we are interested in understanding human brain development, and in particular deciphering what makes it unique. We have developed methods for generating from hiPS cells a tridimensional (3D) preparation resembling the human cerebral cortex, named brain-region specific spheroids or organoids (Nature Methods, 2015; Nature Protocols, 2018; Nature Methods, 2019). These organoids contain functional synapses, non-reactive astrocytes and can be sliced for electrophysiological recordings. They can also be maintained for very long time (>800 days) and display advanced maturation (Neuron, 2017). To investigate how different brain regions talk to each-other in normal and diseased states, we introduced a new approach for in vitro assembly of neural circuits, also known as assembloids (Nature, 2017). We are actively working on modeling in vitro other brain inter-regional interactions (see also our Cell Cinema gallery, an NIH video or recent video material explaining our work (below); also Nature Neuroscience, 2018; Neuron 2018).
Second, we are using state-of-the-art stem cell biology, genome engineering, live imaging and neurobiology approaches in combination with high-throughput in vitro assays to identify dynamical processes that go awry in neural cells derived from patients with neuropsychiatric disorders, such as autism or schizophrenia, and what should be therapeutically targeted in these conditions.
A critical challenge in understanding the intricate programs underlying development, assembly and dysfunction of the human brain is the lack of direct access to intact, functioning human brain tissue for detailed investigation by imaging, recording, and stimulation (Nature, 2018; Science, 2018).
Our lab is using pluripotent stem cells (iPS cells) derived non-invasively from individuals to generate in a dish specific regions of the human brain in a functional 3D preparation we have developed.
We are using months-to-years long ‘brain-a-dish’ cultures (also known as brain region-specific organoids or spheroids) to understand how neurons find their final position in the brain and how they mature functionally.
We are pursuing questions in at least two major inter-related areas:
First, we are interested in understanding human brain development, and in particular deciphering what makes it unique. We have developed methods for generating from hiPS cells a tridimensional (3D) preparation resembling the human cerebral cortex, named brain-region specific spheroids or organoids (Nature Methods, 2015; Nature Protocols, 2018; Nature Methods, 2019). These organoids contain functional synapses, non-reactive astrocytes and can be sliced for electrophysiological recordings. They can also be maintained for very long time (>800 days) and display advanced maturation (Neuron, 2017). To investigate how different brain regions talk to each-other in normal and diseased states, we introduced a new approach for in vitro assembly of neural circuits, also known as assembloids (Nature, 2017). We are actively working on modeling in vitro other brain inter-regional interactions (see also our Cell Cinema gallery, an NIH video or recent video material explaining our work (below); also Nature Neuroscience, 2018; Neuron 2018).
Second, we are using state-of-the-art stem cell biology, genome engineering, live imaging and neurobiology approaches in combination with high-throughput in vitro assays to identify dynamical processes that go awry in neural cells derived from patients with neuropsychiatric disorders, such as autism or schizophrenia, and what should be therapeutically targeted in these conditions.
Stanford Medicine Magazine story featuring our work (2018)
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Minds Wide Open documentary (2018), presenting the work in the Pasca Lab
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Child-X Presentation at Stanford (2018)
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Frontiers in Medicine presentation (2018)
