Spatial Omics Mapping of Human Brain Disorders

Dr. Yang Xiao is a postdoctoral researcher in Biomedical Engineering at Columbia University. She earned her Bachelor’s degree in Molecular Biology at McGill University and pursued her Ph.D. in Biomedical Engineering at Yale University. Under the mentorship of Prof. Rong Fan, Dr. Xiao conducted her doctoral research on brain tumor invasion in the perivascular niche. Employing advanced techniques such as single-cell sequencing and organ-on-a-chip models, her work explained why some primary glioblastoma cells prefer to reside close to vessels while others choose to stay and proliferate in the tumor mass. During her time in Prof. Fan’s lab, Dr. Xiao played a crucial role in the development of innovative spatial platforms (DBiT-seq) for mRNA sequencing and open chromatin sequencing. Upon joining the Kam Leong lab at Columbia, Dr. Xiao’s current research is dedicated to the clinical translation of omics findings, focusing on neurogenomics in psychiatric disorders. Her work involves profiling the postmortem human brains with a cellular and molecular map, with the overarching goal of unraveling the pathological underpinnings of memory and emotion in Major Depressive Disorder. Dr. Xiao’s research contributes significantly to the field of spatial biology, providing insights into the transcriptomic and epigenetic regulatory mechanisms in mood disorders.

Spatial proteomics, transcriptomics, and epigenomics are emerging to bring unprecedented opportunities to dissecting cell types and unraveling regulatory mechanisms of cell states within complex tissues. Despite the human hippocampus being critical for memory and emotion, and its implication in neuropsychiatric disorders, understanding its molecular dysfunction with spatial architecture has been challenging. Our engineering innovation in the spatial mRNA-seq and ATAC-seq platform (DBiT-seq) resulted in the presentation of the first spatial omic atlas of the human hippocampus. Combining with a 25-plex spatial proteomics profiled by CODEX, we introduced a computational framework for studying psychiatric diseases from the perspectives of cell neighborhoods and RNA velocity. This work reveals RNA dynamics in depression, highlighting therapeutic avenues by targeting gene regulatory networks. Our research represents a major leap in the field beyond the single-cell genomic studies of the human brain, establishing a corner stone for future molecular profiling studies with region and organization specific precision.