At the Icahn School of Medicine at Mount Sinai’s Center for Neural Epigenome Engineering, we focus on performing research that will enable us to mechanistically dissect roles for, and then therapeutically manipulate, neuroepigenetic phenomena contributing to disease. We are implementing novel approaches from the fields of chromatin biochemistry, chemical biology, protein engineering, and single-cell omics (including spatial transcriptomics) to achieve these goals. The Center is currently performing investigations in four key areas:

1. Development of novel chemical methodologies to interrogate and manipulate neuroepigenetic/neuroepitranscriptomic phenomena in vivo: We are exploring novel ways in which we can manipulate how chromatin-related proteins interact with DNA to exert function and affect gene expression. The development of novel chemical methodologies to investigate and perturb the basic mechanisms through which these phenomena occur will enable us to advance novel therapeutics to treat disease.
   
   
2. Expansion of molecular, genomics, and proteomics capabilities, with a specific emphasis on the development and implementation of single-cell and spatial sequencing technologies as they apply to the nervous system: The field of single-cell technology enables researchers to look at the genome and gene expression inside many different individual cells simultaneously and study how they operate within a complex framework. This approach is key because the nervous system is not monolithic and researchers must consider how each cell functions not only individually but also in tandem. This strand of research will integrate and develop novel single-cell methodologies to provide insights into how chromatin structures, genes, proteins, and metabolites change in the brain in response to environmental exposures (both adaptive and maladaptive) and how such phenomena contribute to cellular function in both central and peripheral nervous systems.
   
   
3. Use of advanced protein-engineering strategies for causal assessments of underlying chromatin mechanisms responsible for normal neural functions and disease: This branch of investigation explores how we can use a protein’s structure-–specifically chromatin-related protein structures–-to manipulate protein-protein or protein-posttranslational modification interactions for therapeutic use in the context of neurological and/or psychiatric disease. These approaches involve using CRISPR and other epigenome editing technologies for therapeutic use.
   
   
4. Integration of molecular and neural circuitry-based methodologies for in vivo assessments of discovered chromatin mechanisms of brain dysfunction: This strand of research appreciates that neural encoding of complex behaviors requires unique networks of neural ensembles, each of which may arise owing to distinct modes of underlying chromatin regulation. Our research aims to integrate state-of-the-art methodologies in circuit neuroscience with circuit-specific assessments of chromatin/gene regulation to understand how such phenomena contribute to normal physiology and disease.

Our center strives to bring together multiple areas of expertise and encourage collaboration in our quest to better understand chromatin biochemistry, chemical biology, protein engineering, and single-cell omics (including spatial transcriptomics) as they relate to studies of the central and peripheral nervous systems. By leveraging technological innovations to guide mechanistic studies and drug development strategies, this center positions Icahn Mount Sinai to play leadership role in neuroepigenetics and molecular/behavioral neuroscience for many years to come.