Identifying Shared and Unique Molecular Pathways Critical for Cell Fate Decision Across Different Tissues
It is well established that many neurodevelopmental disorder-associated genes influence cell fate decisions and cell states. Our research investigates the molecular and cellular functional roles of NDD-associated genes using CRISPR-based genetic screening, single-cell RNA sequencing, and ATAC-seq in human stem cell-derived neuronal and non-neuronal tissues. This study specifically investigates three questions:
- Which NDD genes functionally impact the development of different cell lineage,
- Whether they act through shared molecular pathways or exert tissue-specific effects, and
- How their disruption alters progenitor cell fate decisions during early lineage specification.
By identifying when and how risk genes converge on common pathways, we gain insight into the origins of multi-organ vulnerability, reveal points of developmental failure, and lay the groundwork for predictive risk models, lineage-targeted interventions, and rational control of cell fate.
Decoding Treatment-Resistant Schizophrenia: Investigating Rare Genetic Variants
Our ongoing research uses CRISPR technology to knock out 12 genes recently identified as rare variants linked to schizophrenia (SCZ), particularly in individuals who exhibit persistent treatment resistance. By generating knockout (KO) lines from patient-derived human induced pluripotent stem cells (hiPSCs), we aim to dissect the cellular and molecular disruptions caused by these variants, focusing on neurodevelopmental pathways and synaptic transmission. This model system allows for a direct comparison of the effects of genetic knockouts on key neural processes and their response to antipsychotic medications. Through these studies, we seek to uncover novel mechanisms driving treatment resistance, which remains a critical barrier to effective intervention in schizophrenia. By bridging the gap between genetic findings and functional outcomes, our research advances the field of precision medicine, offering potential avenues for more personalized therapeutic strategies for psychiatric disorders.
Decoding the Hormonal Modulation of Sex-Biased Genetic Risk in Neuropsychiatric Disorders
This project investigates how estradiol (a form of estrogen) modulates genetic risk for neuropsychiatric and neurodevelopmental disorders through sex-specific effects on gene regulation. By integrating stem cell–derived models, multi-omics approaches, and large-scale genetic datasets, we aim to explain why many psychiatric disorders display sex-biased prevalence, and how hormonal context during early development alters gene expression trajectories linked to disease vulnerability. Our core hypothesis is that estradiol interacts with disorder-associated genetic variants to reshape the transcriptional landscape in neural tissues. These interactions may help explain:
- Sex differences in neuropsychiatric disease prevalence (e.g., higher ASD rates in males),
- Hormonal modulation of gene regulatory networks, and
- Critical developmental windows of vulnerability (e.g., puberty, postpartum, prenatal periods).