Title: The mouse ascending: translating human genetic variation to function
Abstract: Inbred laboratory mice have been only modestly successful in modeling the widely divergent clinical outcomes in human disease, since they capture a narrow subset of the genetic variation found in wild mouse populations. As host genetics plays a significant role in disease susceptibility, pathogenic infection and treatment success, preclinical models that better reflect human genetic variation are crucial for predicting disease course and developing precision therapies. Interbred and outbred panels of laboratory mouse strains that capture higher levels of genetic diversity (“GeDi” mice) better represent allelic variation in human genomes, combining functional analysis of candidate disease variants identified through human genetic studies with the requisite statistical power and resolution for dissecting complex traits in vivo and in derived cell panels. Examples include a wide range of outcomes in neuro-developmental disorders, cardiac repair, metabolic dysfunction and responses to pathogenic infection, underscoring the power of cross-species comparative studies. More recently, new wild-derived mouse panels carrying >40% more variants than classical inbred mouse strains further expand the genomic and phenotypic diversity of preclinical models. These resources combined with gene editing offer exciting prospects for contributing to a future of predictive biology that advances individualized disease prevention and treatment.
Biography: Born in the USA, Professor Nadia Rosenthal obtained her PhD in 1981 from Harvard Medical School and trained as a postdoctoral fellow at NIH, then directed a biomedical research laboratory at Harvard Medical School and served for a decade at the New England Journal of Medicine as editor of the Molecular Medicine series. From 2001 to 2012 she established and directed the EMBL Mouse Biology campus in Rome. She spearheaded the election of Australia to EMBL as its first Associate Member, and in 2008 she founded the Australian Regenerative Medicine Institute (ARMI) at Monash University. ARMI also serves as Headquarters for the EMBL Australia Partner Laboratory Network, of which Rosenthal was Scientific Head. In 2016 she became The Jackson Laboratory’s Scientific Director in Bar Harbor USA. She currently divides her time between Maine and London, where she has held a Chair at Imperial College since 2004.
Rosenthal’s research focuses on muscle and cardiac developmental genetics and the role of growth factors and the immune system in tissue regeneration, with over 300 primary research articles and prominent reviews in high impact international journals including Nature, Science, Cell, New England Journal of Medicine and Scientific American. She is an EMBO member, with numerous awards and honors including the Ferrari-Soave Prize in Cell Biology and Doctors Honoris Causa from the Pierre & Marie Curie University in Paris and the University of Amsterdam. She was an NH&MRC Australia Fellow, is a Fellow of the Academy of Medical Sciences (UK), and Fellow of the Australian Academy of Health and Medical Sciences and has attracted sponsored research funding from major pharmaceutical companies including Amgen, Genzyme, Bristol Myers Squibb and Novartis for her translational studies in regenerative medicine.
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