Many diseases can be described in terms of loss or alterations in identity of specific cell-types and tissues. These include genetic mutations affecting the genome sequence, epigenetic modifications affecting gene expression or inappropriate environmental cues. Such alterations underlie disease states like cancer and metabolic diseases for example diabetes, as well as degenerative pathologies and aging-related conditions. The Who am I? project aim at re-examining pathologies in terms of identity loss with the underlying goal to reveal novel therapeutic strategies based on re-establishing identity.

Developmental Diseases of Specific Tissues

Perturbation of the genetic and epigenetic mechanisms controlling tissue development through key transcriptional programs is responsible for differentiation and morphogenesis defects causing severe human diseases. The Who am I? labex teams will try to improve our understanding of the pathophysiological mechanisms underlying developmental diseases such as diabetes, kidney and  neurodevelopmental diseases as well as endometriosis. The studies will include a combination of developmental, physiopathological, genetic and epigenetic studies in relevant mouse models and further validation in patients to identify the key mechanisms leading to the loss of cellular identity.

Cancer biology

Cellular identity loss may be at the origin of tumorigenesis which often involves de-differentiation of specific cell types. In addition, the interaction between cancer cells and stroma creates a dynamic tumor microenvironment which influence the neoplastic process. The Who am I? teams will investigate these issues in several complementary model systems and focus on: (a) the reprogramming of energy metabolism in tumors, (b) remodeling of the tumor microenvironment, and (c) identification of intrinsic (transcription factors, epigenetic modifications) and extrinsic (environmental clues and signaling pathways) factors which impact on the differentiation status of the tumor and progression towards metastasis.

Social science investigations of identity and disease: between bench and bedside

The Who am I? partners are actively involved in the challenges of translating basic research findings into clinical settings. Animal models for disease can provide an effective path from patient cohorts to novel therapeutic approaches. At both ends of this process, crucial questions about patient welfare arise: the creation of collections of cells/tissues for research purposes raises many ethical and organizational questions, including appropriate standards for informing and obtaining consent from patients; discoveries in the research lab impact on a patient’s options in terms of testing for disease susceptibility and of disease prevention or management (ex. personalized genomic medicine); and innovative genomic technologies offer broader diagnostic capabilities. The Who am I? social science teams will investigate these situations and try to understand how a new and unexpected importance given to a biological component of their identity, affects the way people manage personal, familial, and social components of identity.

Projet porté et financé par :

Qui suis-je? - Le film

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