Molecular Bases of Human Diseases

The department "Molecular Bases of Human Diseases" aims at carrying out high quality research in the fields of immunology and cancer and contributing to improvements in health. Research focus areas include the cellular responses to DNA replication stress, chronic inflammation, cancer, as well as intrinsic and innate immune responses to HIV infection.

Genetic instability and DNA replication stress are characteristic features of tumour cells. These distinct features are exploited therapeutically through stress overload or stress sensitization. Three teams explore how cells respond to DNA replication stress using complementary cell biological, biochemical, proteomics and bioinformatics approaches. DNA damage response mechanisms are explored in human and Xenopus egg extracts. We use proteomic approaches to characterise the composition of replication factories under stressful conditions, and DNA fiber labelling methodologies to visualise and characterise replication dynamics at the single molecule level. We sequence genomic DNA to compare replication-timing profiles and map DNA lesions in normal and cancer cells. Another important aim is to understand how genetic instability and DNA replication stress yield and sustain chronic inflammation, which is a hallmark of tumorigenesis and a poor prognosis factor for cancer patients. The knowledge gained from our research programs is exploited to address drug resistance mechanisms in haematological, breast and brain malignancies.

We aim at understanding the biology of HIV by deciphering the molecular and cellular mechanisms leading to viral persistence (HIV reservoir) and cell resistance (intrinsic and innate immune response). We explore the etiologic factors responsible for the diversity of immune activation profiles in efficiently treated HIV-1 patients, and the morbidities that may be driven by them. The department is home to IMGT®, the international ImMunoGeneTics information system® (University of Montpellier and CNRS), the global reference in immunogenetics and immunoinformatics. IMGT®'s research interests are on molecular immunogenetics, immunoinformatics, bioinformatics and rare human genetic diseases in consanguineous families. IMGT® is used globally by academic and industrial scientists involved in fundamental and medical research as well as in antibody engineering for humanization of therapeutic antibodies.