Heart Engineering & Developmental Genomics et Al. (HEDGe lab)

Our long term vision is improving human sustainable wellbeing. We work to achieve this goal through the integrative application of stem cell biology, gene editing, genomics, and bioengineering to: (1) elucidate the genetic underpinnings of cardiac disease, the #1 killer worldwide; (2) develop regenerative medicine therapy for congenital heart disease, the most common life-threatening malformation in newborns; and, last but not least, (3) provide a cell-based alternative to factory farming, the main cause of biodiversity loss and a central contributor to climate change. These seemingly distinct aspects are actually deeply interconnected: elucidating the gene regulatory mechanisms behind cardiac development and disease provides the knowledge needed to develop cells and tissues for heart remuscularization, which in turn can be produced in even larger scale from animal cells for human consumption. Overall, our work has the potential to improve human life on earth from a holistic perspective: cradle to table and all the way to rocking chair. Our key achievements to date in these three major areas include: (1) elucidating the role of cis and trans nuclear architecture dynamics during both normal heart development and in the pathogenesis of inherited disease (Bertero et al, Nat Commun 2019; Bertero et al JCB 2019); (2) reducing the arrhythmogenic risk of cardiac remuscularization with human pluripotent stem cell-derived cardiomyocytes (patent pending; collaboration between the UW Heart Regeneration Program and Sana Biotechnology); and (3) developing a technology to efficiently and cheaply reprogram pluripotent stem cells into differentiated progenies (patent WO2018096343A1), enabling applications both in the drug screening and cell therapy fields (i.e. bit.bio), and in cellular agriculture (i.e. Meatable). Our current focus is the role of three-dimensional chromatin organization in heart development and disease. We are also building novel genetic tools to probe the structure-function relationship of chromatin compartmentalization. Our work mainly relies on genetic engineering with CRISPR/Cas9, differentiation of human pluripotent stem cells into cardiomyocytes (hPSC-CMs), generation of 3D-engineered heart tissues,determination of nuclear architecture and function with genomic and imaging assays, and analysis of cardiac physiology. Why the et al.? We are immensely worried about the future of our planet in the face of rapidly advancing climate and ecological disasters due to unsustainable human activities. Besides striving for a more sustainable way to do research (i.e recycle and reuse) and travel (i.e. minimize and carbon offset emissions), we place what know-how we have to the service of climate defense. In this light, we wish to try helping combat climate change through cellular agriculture.