Kanishk Jain

The Jain Lab studies how genes are regulated in human cells - the fundamental process that determines which genes are active and which remain silent. Our research focuses on understanding how DNA, which is packaged around histone proteins, becomes accessible for cellular processes like gene expression and DNA repair. We investigate the "Histone Code" — the complex system of chemical modifications that cells use to mark different regions of DNA and control gene activity. By combining traditional biochemical methods with modern genomic and proteomic techniques, we examine how these regulatory mechanisms work both in laboratory conditions and within living cells. Our work explores how gene regulation affects critical cellular functions, including transcription, RNA processing, and the cell's response to DNA damage. When these regulatory systems malfunction, they can contribute to diseases like cancer, so understanding these fundamental processes may lead to new therapeutic strategies. Ultimately, our goal is to uncover the basic principles governing epigenetic regulation and translate this knowledge into improved treatments for human disease.

The Histone Code is governed by a dynamic interplay of "writers," "readers," and "erasers" that regulate processes like transcription, splicing, and the DNA damage response. Writers, such as histone acetyltransferases and methyltransferases, add specific post-translational modifications (PTMs) to histones, while erasers, like histone deacetylases, remove these marks. Readers, including plant homeodomain (PHD) or chromodomain proteins, recognize and bind to these modifications, influencing chromatin structure and recruiting factors involved in gene regulation, splicing machinery, or DNA repair proteins, thereby orchestrating cellular responses. We aim to advance our understanding of chromatin engagement by chromatin readers, writers, and erasers and the implications to human biology by addressing two central themes: 1) Understanding histone reader engagement with chromatin in cancer and 2) Demystifying the complex hierarchy of histone PTMs and their crosstalk.