Brain Research Institute, University of Zurich; Institute of Neurosciences, ETH Zurich
Isabelle Mansuy is Professor in Neuroepigenetics at the Brain Research Institute of the Medical Faculty at the University of Zurich, and at the Institute of Neurosciences of the Department of Health Sciences and Technology at ETH Zurich, Switzerland. Prof. Mansuy is known for her work on the epigenetics of complex brain functions in mammals, particularly on the mechanisms of inheritance of acquired traits across generations. She started her research career working on the molecular mechanisms of memory using conditional transgenic mouse models she established and demonstrated the existence of memory suppressors responsible for forgetting in memory disorders and in aging. Her current research studies the mechanisms by which behavioral and physiological traits can be modified by life experiences, in particular early life trauma, and are passed to descendants via the germline. It aims to identify 1) epigenetic factors in the brain and germ cells underlying the expression and the transmission of behavioral and physiological phenotypes following traumatic stress exposure, 2) the mechanisms responsible for their alterations, 3) the potential reversibility of epigenetic alterations and symptoms induced by traumatic stress, 4) the relevance of findings in mice for human subjects exposed to childhood trauma. Research in the Mansuy lab is pluridisciplinary and uses a combination of environmental and genetic mouse models, epigenetic and genetic methods, behavioral testing, multiomics approaches, bioinformatics, imaging and electrophysiological techniques.
Major research achievements: The Mansuy lab 1) demonstrated the heritability of behavioral and metabolic traits caused by early trauma in the mouse across multiple generations, through both mother and father, 2) identified DNA methylation and non-coding RNAs as epigenetic factors associated with these traits, 3) provided causal evidence that sperm RNA is a vector of inheritance of trauma-induced symptoms. Past achievements of the lab also include research on memory and the identification of protein phosphatases PP1 and calcineurin as memory suppressors that induce forgetting, and their role as epigenetic regulators and modulators of neuronal signaling during memory formation.
Current and future research: Current research focuses on the identification of the ensemble of epigenetic factors in the brain and germ cells associated with the inheritance of trauma-induced traits across generations, on the demonstration of their causal involvement in symptoms and their transmission, and in the study of their modes of induction and maintenance in mice. Research in humans is also conducted in collaboration with clinicians to assess if epigenetic factors identified in the mouse model are altered in patients with childhood or adult trauma. The long-term objectives are to reach sufficient understanding of the mechanisms of epigenetic inheritance to help the design and development of potential diagnostic and therapeutic tools for trauma patients in the clinics. The Mansuy lab is part of various national and international consortia including the HMZ Flagship project STRESS (University Zurich), EarlyCause (Horizon2020), FAMILY (Horizon EU) and HappyMums (Horizon EU), aiming to address the biological and societal aspects of stress in translational research.