Any cell in an organism contains a complete copy of that organism's genome. The difference in structure and function of cells results from silencing of 'unnecessary genes' which occurs in great part epigenetically with DNA methylation being a key mechanism, so that the majority of mammalian DNA is methylated. Taking control over these normal mechanisms is a novel and exciting biomedical challenge and promises broad applicability. Moreover, in disease the aberrant DNA methylation in key regulatory areas (e.g. promoters) inhibiting gene transcription can be an important pathologic mechanism; thus demethylation techniques offer new therapeutic strategies. Finally, DNA methylation abnormalities are increasingly found in numerous pathologies, however we usually cannot say if these abnormalities play a causative role, hence new experimental tools are needed. Thus, increasing appreciation of epigenetics enables new cures and experimental approaches, however certain challenges have been preventing novel therapeutics of this kind.

We design chimeric molecules comprised of DNA demethylases fused with sequence-specific DNA binding domains and use these tools to re-activate or enhance the silenced intrinsic genes in cells. In contrast to existing techniques, such targeted demethylation opens a specific gene promoter to adaptive, context-appropriate activation in situ, and offers superior potential to future therapeutic and modulatory tactics, not only in epigenetically-mediated disease but more broadly where gene function enhancement is desirable. Epigenter is on the cutting edge of epigenetic engineering: we develop protein-based 'biologics' effective when directly administered in vivo. They avoid the need for transgenesis or complex packaging tools with their side effects and regulatory challenges, and thus represent a novel type of epitherapeutics. 

Alexey V. Fedulov MD, PhD, and David J. Gregory PhD, the co-founders of Epigenter, began their collaboration in epigenetic editing when they were researchers at Harvard School of Public Health. The work has continued in Dr. Fedulov’s lab after his transition to faculty at Harvard Medical School, and has expanded after he joined Brown in 2017. Throughout these years Dr. Gregory has been tightly involved into the design and testing of epi-editor constructs as an external consultant. 

Dr. Fedulov is trained as an MD in Internal Medicine and has a PhD in Immunology and Allergy; his postdoctoral training at Harvard focused on epigenetics and inflammation. Dr. Gregory is an Oxford graduate with a PhD in gene expression from the University of Dundee; he has trained at McGill and Harvard in host-pathogen interactions.