Non-Enzymatic Covalent Modifications (NECMs) on Histones
We are interested in the effect non-enzymatic covalent modifications (NECMs) have on the epigenetic landscape, cellular fate, and their implications in disease.
Characterization of Linker Histone H1 Variants
The linker histone H1 is a fundamental component of chromatin that is critical in regulating the higher order structuring of the eukaryotic genome. There are several subtypes of human H1; the David lab is interested in characterizing the functional variability of human H1 variants.
Non-Canonical Histone Ubiquitination
Despite the identification of 40+ ubiquitination sites on histones in vivo, only a fraction of these have been studied in detail. We are interested in elucidating the readers, writers, and erasers of these marks, with the goal of understanding their biological significance and functional output.
Chromatin (mis)regulation during Hepatitis B Virus infection
Hepatitis B Virus (HBV) chronically affects more than 250 million people worldwide. Two key elements of the HBV life cycle contribute to the development chronic infections and correlate with the severity of disease progression: the establishment of a viral minichromosome of covalently closed circular (ccc) DNA within infected hepatocytes, and the expression of the regulatory protein HBx. Interestingly, HBx in the nucleus redirects host epigenetic machinery to activate cccDNA expression. We seek to better understand the molecular mechanisms behind this misregulated chromatin signaling in HBV infection.
Methods to engineer proteins in vivo
We develop methods that bring the precision and flexibility of synthetic chemistry to a native chromatin context using newly identified ultra-fast split inteins. We apply these methods toward the traceless and site-specific labeling of histones with native and synthetic modifications live cells. In addition, we are expanding our in cellulo method to animal models, illustrating the direct manipulation of histones in a tissue-specific manner. With these in vitro and in vivo methods we aim to characterize new classes of histone modifications and their direct role in regulating transcription in healthy and disease states.