Cleber Trujillo,
Project Scientist,
University of California San Diego
Since 2001, I have investigated the role of neurotransmitters in neural physiology and development. Using mouse and human neural stem cells as model systems and in combination with a state-of-art molecular and cellular techniques, I explored novel pathways and therapeutic targets for neurodevelopmental disorders, including autism, and Rett Syndrome. While studying neurogenesis and neurotransmission signaling at the University of São Paulo, I developed an interest in modeling neurodevelopmental disorders. At the University of California – San Diego (2011), I took advantage of reprogramming technologies to generate iPSCs to recapitulate early stages of the human MECP2 Duplication Syndrome, showing a promising cellular tool to facilitate therapeutic drug screening for severe neurodevelopmental disorders. The iPSC model was also used to fill in the current knowledge gap in Williams Syndrome cellular biology and lead to further insights into the molecular mechanism underlying the disorder and the human social brain. Currently, I am a Project Scientist at the UCSD studying the formation of human network using brain organoids during development and disease conditions.
Applications of Brain-Model Technology to Study Neuro-developmental Disorders
Tuesday, 15 October 2019 at 11:30
Add to Calendar ▼2019-10-15 11:30:002019-10-15 12:30:00Europe/LondonApplications of Brain-Model Technology to Study Neuro-developmental DisordersStem Cells in Drug Discovery Tox and Organoids 2019 in Coronado Island, CaliforniaCoronado Island, CaliforniaSELECTBIOenquiries@selectbiosciences.com
The complexity of the human brain permits the development of
sophisticated behavioral repertoires, such as language, tool use,
self-awareness, and consciousness. Understanding what produces neuronal
diversification during brain development has been a longstanding
challenge for neuroscientists and may bring insights into the evolution
of human cognition. We have been using stem cell-derived brain model
technology to gain insights into several biological processes, such as
human neurodevelopment and autism spectrum disorders. The reconstruction
of human synchronized network activity in a dish can help to understand
how neural network oscillations might contribute to the social brain.
Here, we developed cortical organoids that exhibit low-frequency
network-synchronized oscillations. Periodic and highly regularized
oscillatory network events emerged after 4 months, followed by a
transition to irregular and spatiotemporally complex activity by 8
months, mimicking features of late-stage preterm infant
electroencephalography. Furthermore, we found that the
Methyl-CpG-binding protein 2 (MECP2) is essential for the emergence of
network oscillations, suggesting that functional maturation might be
compromised at early stages of neurodevelopment in MECP2-related
disorders, such as Rett syndrome, autism, and schizophrenia. As evidence
of potential network maturation, oscillatory activity subsequently
transitioned to more spatiotemporally irregular patterns, capturing
features observed in preterm human electroencephalography (EEG). These
results show that the development of structured network activity in the
human neocortex may follow stable genetic programming, even in the
absence of external or subcortical inputs. Our model provides novel
opportunities for investigating and manipulating the role of network
activity in the developing human cortex.
Add to Calendar ▼2019-10-14 00:00:002019-10-15 00:00:00Europe/LondonStem Cells in Drug Discovery Tox and Organoids 2019Stem Cells in Drug Discovery Tox and Organoids 2019 in Coronado Island, CaliforniaCoronado Island, CaliforniaSELECTBIOenquiries@selectbiosciences.com