Marco Osterwalder
University of Bern, Lawrence Berkeley National Laboratory, University of Basel
Research areas: Biochemistry, Genetics and Molecular Biology · Molecular Biology · Developmental Biology and Gene Regulation · Genomics and Chromatin Dynamics · Congenital heart defects research
0000-0002-1969-2313
About
I am a Developmental Biologist with a background in Developmental Genetics and Functional Genomics studying the gene regulatory and epigenetic mechanisms underlying Cardiac Development and Heart Disease.
I obtained my Bachelor of Science (B.Sc.) degree in Molecular Biology at the Biozentrum of the University of Basel, Switzerland, in 2006 and my Master of Science (M.Sc) degree in Molecular Biology at the University of Basel in 2007.
In 2008, I joined the Developmental Genetics lab of Prof. Rolf Zeller at the Department of Biomedicine (DBM) of the University of Basel as a PhD student to work on novel genome engineering methods and to study gene networks controlling mouse embryonic limb development. During my PhD, I developed a novel genetic engineering approach in stem cells termed dual recombinase-mediated cassette exchange (dRMCE) published in Nature Methods and directly took advantage of the tool to generate a mouse model encoding an epitope-tagged version of the HAND2 transcription factor (TF) gene allowing to identify genome-wide target genes during limb morphogenesis.
In 2014, I joined the Mammalian Functional Genomics Lab of Axel Visel and Len Pennacchio at Lawrence Berkeley National Laboratory (LBNL), California, USA, as a postdoctoral fellow to study the role of transcriptional enhancers in embryonic organogenesis. During this period, with the support of two postdoctoral mobility fellowships from the Swiss National Science Foundation (SNSF), I led a widely cited study in gene regulation revealing mechanisms of enhancer redundancy and phenotypic robustness, which was published in Nature. Additionally, I co-authored several high-impact publications defining tissue-specific in vivo enhancer landscapes and uncovering how enhancer-related genomic variation contributes to congenital craniofacial or limb malformations. Following a position as Project Scientist at LBNL from 2018-2019, I was awarded an Eccellenza Professorial Fellowship by SNSF, with the Department for BioMedical Research (DBMR) at the University of Bern as host institution.
Since 2020, I am an independent research group leader at the DBMR, integrated in the cardiovascular disease (CVD) program, supported additionally by the Cardiology Department of the Bern University Hospital and the Department of Anatomy at the University of Bern. My group's research focuses on the functional dissection of cardiac enhancer landscapes and the 3D genomic architecture that orchestrates dynamic and cell type specific transcription of cardiac genes, aiming to unravel the gene regulatory mechanisms underlying mammalian heart development and congenital heart defects. Within the scope of our HeartX program funded by the SNSF NRP79 (“Advancing 3R”), we have recently also developed human iPSC-derived cardiac organoids as an in vitro model to investigate aspects of human cardiogenesis and mechanisms of heart disease. This achievements enabled additional collaborations with research groups specializing in cardiac channelopathies or cardiomyopathies, as evidenced by participation in the lighthouse project "PACE" funded by the Bern Center for Precision Medicine (BCPM).
Employment
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University of Bern Research Group Leader2025 - Present
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University of Bern SNSF Eccellenza Assistant Professor2020 - 2025
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Lawrence Berkeley National Laboratory Senior Postdoctoral Researcher / Project Scientist2017 - 2019
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Lawrence Berkeley National Laboratory SNSF Postdoctoral Fellow2014 - 2017
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University of Basel Postdoctoral Fellow2012 - 2014
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University of Basel Ph.D. Student2008 - 2012
Education
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University of Bern Habilitation (Venia Docendi) in Developmental Biology2025 - Present
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University of Basel PhD in Cell Biology (‘summa cum laude’)2008 - 2012
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University of Basel Master of Science (M.Sc.) in Molecular Biology2006 - 2007
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University of Basel Bachelor of Science (B.Sc.) in Molecular Biology2003 - 2006
Projects & Funding
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Precision Diagnosis and Therapy in Cardiac Channelopathies (PACE) Bern Center for Precision Medicine, University of Bern2024 - 2026
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HeartX: Decoding cardiac regulatory landscapes in an all-human model for cardiogenesis. Swiss National Science Foundation2022 - 2025
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The cis-regulatory dynamics controlling Mef2C in mammalian heart morphogenesis Novartis Foundation2022 - 2023
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Cardiac malformations and arrhythmias: understanding the role of TBX5 enhancers. Swiss Heart Foundation2021 - 2022
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Regulatory dynamics of heart formation and in vivo cardiac reprogramming Swiss National Science Foundation2020 - 2025
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Discovery and functional characterization of cell-type specific and subregional enhancers in mammalian heart development. Swiss National Science Foundation2016 - 2017
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Large-scale identification of the enhancers driving subregional gene expression programmes in the developing heart. Swiss National Science Foundation2014 - 2016
Publications (33)
- Development of a laser injury model using human cardiac spheroids Save
- Uncovering hidden enhancers through unbiased in vivo testing. Save
- A gene desert required for regulatory control of pleiotropic Shox2 expression and embryonic survival Save
- Dynamic enhancer landscapes in human craniofacial development Save
- Identification and characterization of Hand2 upstream genomic enhancers active in developing stomach and limbs Save
- A spatio-temporally constrained gene regulatory network directed by PBX1/2 acquires limb patterning specificity via HAND2 Save
- Single cell evaluation of endocardial Hand2 gene regulatory networks reveals HAND2-dependent pathways that impact cardiac morphogenesis. Save
- Wt1 transcription factor impairs cardiomyocyte specification and drives a phenotypic switch from myocardium to epicardium. Save
- Characterization of Mammalian In Vivo Enhancers Using Mouse Transgenesis and CRISPR Genome Editing. Save
- HAND transcription factors cooperatively specify the aorta and pulmonary trunk. Save
- Bi-fated tendon-to-bone attachment cells are regulated by shared enhancers and KLF transcription factors. Save
- The mole genome reveals regulatory rearrangements associated with adaptive intersexuality. Save
- Loss of Extreme Long-Range Enhancers in Human Neural Crest Drives a Craniofacial Disorder. Save
- Bi-fated tendon-to-bone attachment cells are regulated by shared enhancers and KLF transcription factors Save
- Interrogating the Grainyhead-like 2 (Grhl2) genomic locus identifies an enhancer element that regulates palatogenesis in mouse Save
- Noncoding deletions reveal a gene that is critical for intestinal function. Save
- Cardiac Reprogramming Factors Synergistically Activate Genome-wide Cardiogenic Stage-Specific Enhancers. Save
- Enhancer redundancy provides phenotypic robustness in mammalian development. Save
- Ultraconserved Enhancers Are Required for Normal Development. Save
- Composition and dosage of a multipartite enhancer cluster control developmental expression of Ihh (Indian hedgehog). Save