Yann Herault’s principal interest is in the genetics of intellectual disabilities (ID) and autism spectrum disorder (ASD). He has worked on Down syndrome (DS) and other ID caused by copy number variation. His overall aim is to better understand the pathophysiology of these disorders and develop preclinical approaches to reduce their consequences on cognition and behavior.
Herault’s current expertise is in understanding the neurobiology of DS and developing potential therapeutics. His lab’s findings have contributed to the demonstration that neuronal excitation/inhibition imbalance in mouse models of DS can be compensated with GABA inverse agonist treatment. His group also showed that the increased dose of the Dyrk1a gene located on chromosome 21 can be alleviated in mouse models with a polyphenol derived from green tea or new chemical inhibitors targeting the kinase activity of the encoded protein.
Working with human geneticists who have identified new mutations in rare IDs, Herault and his colleagues have continued to generate and study animal models for ID and ASD. He has also developed models to better understand the 16p11.2 and 17q21.31 syndromes, as well as the role of Ptchd1 and additional genes involved in ID and ASD.
As a mouse geneticist, he is also leading the Mouse Clinical Institute with a staff of 100 people — mostly staff scientists, engineers and technicians. The center is making more than 250 mouse models per year and are now developing rat models for genetic disorders, including ASD. The center’s achievements are evident by the success of the French national infrastructure networks CELPHEDIA (Creation, Breeding, Phenotyping, Distribution and Archiving of model organisms) and PHENOMIN (French National Infrastructure for Mouse Phenogenomics), its partnership with INFRAFRONTIER (the European Research Infrastructure for the generation, phenotyping, archiving and distribution of model mammalian genomes) and long-standing collaborations with biopharmaceutical companies.