Karolinska Institutet (SWE)/Yale University School of Medicine (USA); Senior Researcher/Associate Professor

Makoto Sahara

Research Specialist

MD, PhD, FAHA
Principal Senior Researcher/
Associate Professor
Karolinska Institutet (SWE)/
Yale University School of Medicine (USA)

About me

  • Cardiovascular & General Physician
  • Basic Scientist in Stem Cell and Computational Biology, Molecular and Developmental Cardiology, and Cardiovascular Regenerative Medicine
  • Fellow of the American Heart Association
  • Fellow of the Japanese Society of Internal Medicine
  • Fellow of the Japanese Circulation Society

Research description

Cardiac outflow tract defects are the most important cause of human congenital heart disease (CHD), the most common malformation in children affecting 1/100 live births. Mal-alignment of the underlying cono-ventricular region with the overlying great vessels results in several serious forms of CHD. While many genes that cause CHD have been identified, the precise mechanisms that link these gene variants with specific cardiac malformations are largely unknown. The central hypothesis of Dr. Sahara's research projects is that a novel subset of human cono-ventricular progenitors, e.g., human cardiac outflow tract-specific LGR5/ISL1+ progenitors that our group has recently discovered through single-cell omics studies and their downstream progeny would play a critical role in guiding human outflow tract formation through their alignment, migration, expansion, and paracrine guidance cues, and that defects within this specific subset and its functional molecular pathway may play a major causative role in the pathogenesis of human CHD. Thus, Dr. Sahara's research aim is to first identify more causative CHD genes through cross-referencing single outflow tract progenitors’ RNA/DNA sequencing data obtained from various species during mammalian cardiogenesis with other huge databases showing the existing landscape of human CHD mutations (e.g., Yale's PCGC). The objective is to establish specific pathways that link gene disorders with specific defects in the outflow tract progenitor pool and thereby each morphologic phenotype of CHD, leading to the design of new strategies to mitigate the serious forms of the disease.  Collectively, the long-term goals of Dr. Sahara and his research team are: 1) To understand the biology of discrete cardiovascular progenitors and paracrine mediators that are uniquely identified from the single-cell omics studies in the mammalian developing heart and vasculature; 2) To identify specific pathways that link gene disorders with specific defects in the cardiovascular progenitor pool and each morphologic subtype of human congenital cardiovascular malformations; and 3) To develop novel therapeutic approaches combining the novel cardiovascular progenitors with chemically modified mRNA of defined factors for regeneration and structural repair against congenital and acquired cardiovascular disease.

Education

PhD: Tokyo University (2007)

MD: Osaka University (1998)

Academic honours, awards and prizes

11/2005 Best Abstract Award, American Heart Association Scientific Sessions [Dallas]

06/2006 YOUNG INVESTIGATOR AWARD, The International Society for Stem Cell Research (ISSCR) Scientific Sessions [Toronto]

03/2007 YOUNG INVESTIGATOR AWARD, Japanese Circulation Society Scientific Sessions [Kobe]

03/2010 Fellowship Program, Banyu Life Science Foundation International

12/2015 & 2019 Research Project, Hjärt-Lungfonden

10/2016 & 2018 & 2020 KI Research Foundation G

10/2019 Research Project, Vetenskapsrådet

03/2020 Junior StratRegen Award

 

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