The development of the human brain, particularly the neocortex, has been precisely regulated by both genetics and environmental factors, including internal factors, for example, signals, cytokines, hormones, extracellular matrix; as well as external factors, such as oxygen, virus, and toxins. This is a fragile process, any tiny wrongs can lead to mild to severe brain disorders with cognitive or structure phenotypes, heavily affecting the regular life of the kids and their families, represented by the spectrum of pediatric developmental disorders. At the same time, it is a tough process with incredible resilience to self-protect and recovery, with the best of examples of kids who have been suffering and recovering from the prenatal stroke.
Topic 1: The roles of non-neuronal cells in the developing human brain and related disorders
My previous works as well as many others highlighting the accumulating importance of non-neuronal cells in neocortical development (Wang et.al 2024, Wang et.al 2021 PMID: 34244682), few answers respond to why and how these cells impact brain development and contribute to pathogenesis of developmental disorders. These knowledge gaps limited a comprehensive understanding of diseases pathogenesis, banding our hands for therapeutic interventions. To fill these gaps and to contribute treatment, we aim to demonstrating the roles of non-neuronal cells in developing human brain and related disorders. Our current focus is on pericytes, astrocytes and epilepsy.
Topic 2: How environmental factors contribute to disease pathogenesis
Despite the fast-moving whole exome/genome sequencing (WE/GS) field, still more than half of patients with NDDs remain without genetic diagnosis even after genetic assessment. Moreover, even in those cases where a responsible gene is identified, a model has been built, very few results in a change in care or new therapy (Wang et.al 2020 PMID: 32788587; Wang et.al 2023 PMID: 36669109; Wang et.al 2023 PMID: 36759260). Based on my previous works, I believe a limited understanding of the contributions of environmental factors and how do these factors coordinate with genetic mutations sets the key hurdle. To bridge the knowledge gaps, we aim to reveal the how do environmental factors contribute to disease pathogenesis, and how do they interact with genetic alterations, utilizing stem cell based model and functional genetics. We current focus on oxygen and fetal exposure to drug.
Topic 3: Building stem cell-based models to advance understanding of the roles of the nervous system in childhood tumors
Childhood tumors (or pediatric tumors), particularly the brain tumor, are usually devastating abnormality in children, ranking as the second to leukemia as a cause of pediatric malignancies. However, till today the diagnosis, care, and treatment response to these tumors are mostly open questions waiting for investigation. Noteworthy progress has been made on this topic in the past few years in a perspective of cancer biology. Although, the role of nerve system in tumors is increasingly appreciated, large gaps remain. We, therefore, aim to build stem cell based model with “proof of concept animal models” to advance the roles of nerve system in childhood tumors in brain, head, and face. We currently focus on medulloblastoma (MB), a type of embryonic brain tumor in the cerebellum.