Sociality is a key aspect of human behavior and its deficits are found in many mental illnesses, such as autism spectrum disorder. The Geng lab studies the molecular basis of social behavior and its implications on mental illnesses. The bulk of our work utilizes two unique systems developed in our lab: a novel zebrafish model of sociality that is amendable to high-throughput screening, and a high-resolution behavioral analysis platform based on deep learning. We also validate our zebrafish findings in rodent and stem cell models. A current focus of the lab is to systematically discover environmental toxins that contribute to the risk of autism through a large-scale chemical screen.
Geng lab's current research projects include:
Elucidating how Topoisomerase II-alpha (Top2a) functions as a master regulator of social development. My postdoctoral work discovered Top2a as a master control gene for social development through the first large-scale screen for environmental regulators of sociality. Numerous environmental chemicals (toxins, medication, plant products) are known to inhibit Top2a and have shown social-inhibitory effects in our experimental models. Our preliminary genomics and epidemiology studies suggest a causal relationship between Top2a inhibition and elevated risk for autism. Our genomics analysis points to polycomb repressive complex 2 (PRC2) as a downstream effector of Top2a inhibition, and inhibiting PRC2 did successfully rescue social deficits caused by Top2a inhibition in zebrafish, suggesting a potential therapeutic strategy for a subset of autism patients. We are now working to examine the rescue effects of PRC2-inhibition in rodents and to elucidate the molecular mechanism of Top2a in the context of social development using a variety of approaches.
Systematic discovery of environmental risk factors for social deficits and autism. Approximately 40% of autism risk are contributed by environmental factors, yet we know very little about what these factors are. The Geng lab is conducting a high-throughput screen of over 4,000 known environmental toxins from the ToxCast library - a comprehensive chemical collection curated by the EPA - to systematically discover environmental chemicals that can negatively impact the development of social behavior and potentially lead to increased autism risk.
High-resolution behavioral analysis and drug discovery through deep learning. Subtle but stereotypical behavioral changes are often associated with mental illnesses, such as the restricted and repetitive behaviors in autism patients and "tics" in people suffer from Tourette syndrome. However, automated detection of such behavioral traits in animal models of diseases has been prove challenging. The Geng lab is working on using a unique unsupervised deep learning approach to automatically detect and classify subtle behavioral changes in animal models of mental illnesses, with the goal of facilitating drug discovery for these diseases.
