Momoko Watanabe, Ph.D.
Momoko Watanabe, Ph.D.
Momoko Watanabe earned a B.S. in Molecular, Cell, and Developmental Biology from the University of California, Los Angeles (UCLA) in 2006. She then pursued her doctoral studies at UC Irvine, where she studied the mechanisms of forebrain patterning and used in vivo developmental principles to derive choroid plexus epithelial cells from mouse and human pluripotent stem cells (PSCs) for cell-based therapeutic applications. Building on her excitement and experience with neural development and stem cell biology, she did her first post-doctoral training at RIKEN Center for Developmental Biology in Japan, to focus on the three-dimensional culture of cerebral cortex structures, so called brain organoids, generated from hPSCs. She then moved back to the U.S. and joined UCLA. Her project focused on the development of highly efficient and reproducible cerebral organoid methods to investigate the origins of cortical neural circuits and model neurodevelopmental disorders, including the Congenital Zika Syndrome. Building upon these accomplishments, she successfully received a NIH K99/R00 grant from the National Institute of Child Health and Human Development (NICHD). She was recently recruited to UC Irvine as a part of Faculty Hiring for Leveraged Research Excellence (FHLRE) “Stem Cells in Tissue Engineering” and started as an Assistant Professor at the Anatomy and Neurobiology Department in 2020. She is very excited to contribute to a synergistic interdepartmental concentration in stem cell-based engineering.
Research in Lay Terms
Most neurological disorders such as autism and Alzheimer’s disease are distinct to humans and rarely seen in animals. In order to find cures to these human-specific disorders, a human brain model is ideal. However, human fetal and adult tissues are difficult to obtain and conduct experiments with. A viable solution to this problem has emerged through the development of methods for making human brain tissues in a dish from stem cells. These so-called “mini-brains” or “organoids” have three-dimensional structure and exhibit neural activities reminiscent of those seen in the brain within the body. The Watanabe Laboratory established robust and highly efficient methods for making mini-brains and determined how well they match different stages in human brain development. The Watanabe Laboratory also confirmed that neural networks formed in mini-brains recapitulate key features of neural circuits in the intact brain. Furthermore, this mini-brain system provides unprecedented opportunities to study how genetic and environmental insults impact human brain development and function. The Watanabe Laboratory uses the mini-brain system to investigate neural activities and circuit formation that have tremendous implications in human specific disorders such as neuropsychiatric and neurodegenerative diseases. The Watanabe Laboratory can make mini-brains from stem cells isolated from patients suffering from neurological diseases to determine the underlying causes and cures for these conditions.
She has set out in her near future work to address three main aims: 1) create a powerful organ-on-a-chip systems to improve the established brain organoids, 2) develop a brain organoid model for neurodevelopmental disorders, and 3) define the microcircuit properties of brain organoids as a model system for human brain activities.
It is intriguing how a single fertilized egg divides and gives rise to an organism containing a diverse array of cells, tissues, and organs with beautiful three-dimensional (3D) architecture in a precise manner. The forebrain is of particular interest because it is highly-specialized structure with features that are markedly different between species. For example, the cerebral cortex in primates is enormously increased in size and complexity, which probably endow humans with remarkable sensory activities and intellectual ability such as abstract thinking and creativity. Understanding human neural development is important for not only to gain some evolutionary insights but also to discover the underlying causes of human-specific diseases such as neurodevelopmental, neurodegenerative, and neuropsychiatric disorders. A human brain model is deal, given that rodent models sometimes fail to mimic human symptoms and predict clinical outcomes. However, due to limited access to human brain tissue and ethical concerns, it has been challenging to directly study human development. Consequently, considerable attention has been placed on the generation of in vitro models using human pluripotent stem cells (hPSCs) to recapitulate aspects of human development and disease. The cerebral organoid is a 3D cortical tissue derived from hPSCs and recapitulates laminar organization of the developing cerebral cortex in vivo. The advent of such organoid techniques has opened the door for studies of human specific developmental features and paves the way for disease modeling. The goal of the Watanabe lab is 1) to use this robust organoid system to uncover microcircuit formation that has the underlying importance for human brain activities and its malfunction is likely link to neuropsychiatric disorders, and 2) to study autism spectrum disorder (ASD), the most common heritable form of cognitive impairment and known to have interneuronopathies. By utilizing cortical-ganglionic eminence fused-organoids, we study the full inhibitory and excitatory neuronal microcircuits to model ASD, using patient derived hPSCs. This project will likely give some human specific insights into mechanisms and cures of this disease.