Marchiano S, Nakamura K, Reinecke H, Neidig L, Lai M, Kadota S, Perbellini F, Yang X, … [15 authors], Kattman S, Thies RS, Sniadecki N, MacLellan WR, Bertero A #, Murry CE #@ (2023). Gene editing to prevent ventricular arrhythmias associatedwith cardiomyocyte cell therapy. Cell Stem Cell 30, 396-414

    This manuscript reported a strategy to overcome a major roadblock towards the clinical translation of cell therapy to remuscolarize the injured heart. We mechanistically dissected the electrophysiological network that underlie engraftment-associated arrhythmia, and we generated a cell line that no longer leads to this complication while maintaining the ability to engraft and electrically couple with the host tissue.

    Bertero A, Fields PA, Ramani V, Bonora G, Yardimci GG, Reinecke H, Pabon L, Noble WS, Shendure J, and Murry CE. Dynamics of genome reorganization during human cardiogenesis reveal an RBM20-dependent splicing factory. Nature Communications, 2019.

    This manuscript uncovered that inter-chromosomal (trans) chromatin organization is not just stochastic yet can be pivotal in gene regulation.

    Bertero A, Fields PA, Smith AS, Leonard A, Beussman K, Sniadecki NJ, Kim D-H, Tse H-F, Pabon L, Shendure J, Noble WS, and Murry CE. Chromatin compartment dynamics in a haploinsufficient model of cardiac laminopathy. Journal of Cell Biology, 2019.

    This work demonstrated how chromatin organization plays roles that are not just structural yet can be functional in human development and disease.

    Bertero A, Brown S, Madrigal P, Osnato A, Ortmann D, Yiangou L, Kadiwala J, Hubner NC, de Los Mozos IR, Sadee C, Lenaerts A-S, Nakanoh S, Grandy R, Farnell E, Ule J, Stunnenberg HG, Mendjan S, and Vallier L. The SMAD2/3 interactome reveals that TGFβ controls m6A mRNA methylation in pluripotency. Nature, 2018.

    This paper demonstrated how epigenetic and epitranscriptomic regulations can be interconnected by transcription factors.

    Fogarty NME, McCarthy A, Snijders KE, Powell BE, Kubikova N, Blakeley P, Lea R, Elder K, Wamaitha SE, Kim D, Maciulyte V, Kleinjung J, Kim J-S, Wells D, Vallier L, Bertero A, Turner JMA, and Niakan KK. Genome editing reveals a role for OCT4 in human embryogenesis. Nature, 2017.

    This was the first report of gene editing in human embryos to unravel species-specific regulatory networks.


    ERC Starting Grant, 2022

    Career Development Award, Giovanni Armenise-Harvard Foundation, 2021

    Long-Term Fellowship, European Molecular Biology Organization, 2017

    MRes-PhD Studentship in Cardiovascular Research, British Heart Foundation, 2011

    Distinction Award for Master Dissertation, University of Turin, 2011

    Summer Research Program Scholarship, École Polytechnique Fédérale de Lausanne, 2009

Career Development Award Project Title

Functional dynamics of chromatin topology in congenital heart disease, 2021

Who he is

Alessandro Bertero is a group leader at the Molecular Biotechnology Center of the University of Turin, and an Associate Professor in the Department of Molecular Biotechnology and Health Sciences. He began his training with the late Guido Tarone at the University of Turin in Italy, where he investigated the Melusin signalling pathway in cardiac hypertrophy and obtained a BSci (2009) and an MSci (2011). Having being awarded a British Heart Foundation Graduate Fellowship, he moved to the University of Cambridge in the UK. Working with Ludovic Vallier he obtained an MRes (2012) and a PhD (2016) by studying the mechanisms by which TGF beta signalling controls early differentiation of human pluripotent stem cells. Alessandro performed his postdoctoral training with Chuck Murry at the University of Washington in the US with the support of an EMBO Long-Term Fellowship (2017). During this time he determined the role of three dimensional chromatin organization dynamics during human cardiogenesis and in inherited dilated cardiomyopathy. Alessandro launched his group at the UW Institute for Stem Cell and Regenerative Medicine in 2019. In 2021, he relocated the lab to his alma mater in Italy thanks to the Giovanni Armenise-Harvard Foundation Career Development Award. He now leads the Armenise-Harvard Laboratory of Heart Engineering & Developmental Genomics et al (HEDGe lab). Alessandro has also secured an ERC Starting Grant (2022), among other intra and extramural project support.

What he does

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., and in cellular agriculture (i.e. Meatable).

News from the Lab

Current efforts in the group focus on the role of three-dimensional chromatin organization in normal and abnormal heart development, and in inherited cardiomyopathy. We are also building novel genetic tools to probe the structure-function relationship of chromatin compartmentalization. Finally, we are applying synthetic biology tricks to generate self-sustaining and cheap-to-differentiate fish stem cells.