Our lab develops technologies to understand how human genetic variants cause diseases of the nervous system and cancer. We use a multi-disciplinary approach, combining genome engineering, pooled genetic screens, bioinformatics, electrophysiology, and imaging, to dissect the inner workings of the human genome and its dysfunction in autism and tumor evolution.
We have capitalized on new technologies for large-scale DNA synthesis, gene editing and next-generation sequencing to develop pooled libraries of RNA-guided nucleases (e.g. CRISPR) for forward genetic screens (see figure below). By targeting all protein-coding genes in human/mouse genomes, we have identified novel genetic drivers of melanoma drug resistance, drivers of metastasis in vivo, and mechanisms used by tumors to evade immunotherapy.
Recently, we have developed pooled CRISPR libraries and gene editing approaches to target the noncoding genome. A major goal of our work is to understand the functional consequences of modifying noncoding elements in their native context and how they relate to existing hallmarks of noncoding function such as transcription factor binding, enhancer marks and physical genome structure. Previous/current projects include applications in cancer, neurodevelopmental disorders (using human stem cells and neurons) and hemoglobin regulation. We plan to continue expanding the genome engineering toolbox to further our understanding of the noncoding genome and its role in human health and disease.
To find out more about current projects and open positions in the Sanjana lab, please visit the lab webpage.