Student Profile: Denise Robles

Research Summary
Autism is a lifetime neurodevelopmental condition beginning in early childhood which impairs an individual’s ability to communicate with others and affects approximately 1 in 59 children worldwide. Although the condition still remains poorly understood, major advancements have been made in determining genetic and developmental origins by pinpointing implicated genes and chromosomal syndromes. Efforts to accurately model this condition involve the use of human-induced pluripotent stem (hiPS) cells from patients carrying the identified genetic predisposition. However, existing animal models and traditional two-dimensional cell culture-based models do not adequately represent the native human brain architecture. Cerebral organoids composed of hiPS cell-derived neural progenitor cells self-assemble and mature into a three-dimensional neural architecture, and may provide an improved model of neural circuit activity. Since the brain is not accessible to direct experimentation, cerebral organoids present a unique opportunity to model human brain development and function between brain regions. Although there has been extensive research in the application of micro-fabrication and -fluidic principles to develop physiologically relevant platforms for two-dimensional cell cultures, there is limited work on platforms for three-dimensional organoid cultures. In an effort to lend organoid cultures better characterization potential, long-term culturing periods, and financial feasibility, this work focuses on the development of a complete perfusion system. Development of this cerebral organoid platform has the potential to provide important insight into the effect of neurodevelopmental disorders on neuronal connectivity, viability, and synaptic plasticity. The goal of this project is to engineer a system to closely model brain network circuitry using cerebral organoids derived from patient-specific iPS cells to enable investigation into the mechanisms underlying the pathophysiology.