We uncover how MECP2 and RNA polymerase II form dynamic transcriptional hubs that control gene expression in neurons. By integrating proteomics, structural biology, CRISPR-based genetic screens, and advanced imaging, we map the molecular partnerships and condensate assemblies that drive transcription. This work reveals how Rett syndrome mutations disrupt transcriptional hubs and paves the way for small-molecule strategies to restore healthy neuronal gene regulation.

We investigate how autism-associated transcription factors (TFs) control neuronal gene regulation by mapping their genome-wide occupancy and DNA-binding specificity. Using single-cell CUT&Tag and transcriptomics, we define how these factors orchestrate gene programs in patient-derived neurons, organoids, and postmortem human brain tissue. Determining how mutations in TFs or in their DNA binding sites perturb gene regulation is central to understanding phenotypic variation and disease. This knowledge will provide critical foundations for precision medicine approaches in autism spectrum disorders.   

Melanoma causes most skin cancer deaths due to its high metastatic potential and resistance to current immunotherapies. To address this, we have created a unique human-mouse chimera model that supports long-term melanoma growth in an immune-competent host. This system captures the progression from immune activation to immunosuppression, enabling direct comparisons with existing preclinical models. Using spatial transcriptomics, we reveal human-specific tumor–immune interactions to guide next-generation immunotherapies for solid tumors.