Hugues de Thé works on the relationship between gene transcription, nucleus architecture dans cancer genesis. After discovering retinoid acid receptor and the first response element of this pathway during his PhD thesis in Pasteur Institute, he brought a key contribution of the characterization of PML/RARA, a fusion gene responsible of promyeloid acute leukemia (PAL). He then focused on the study of PML/RARA protein role, which has negative dominant effects on transcription (blocking cell differenciation) and on the nucleus body organization (promoting proliferation).
He demonstrated that two drugs used in PAL, arsenic and retinoic acid induce PML/RARA protein degradation, arsenic targeting the PML section and retinoid acid the RARA section of the protein. Using animal models of leukemia, he demonstrated that inducing the degradation of PML/RARA was responsible for the clinical effect of these drugs and that the combination may cure the disease.
Clinical trials directly inspired by his work have led to the successful treatment of many patient, making PAL one of the first example of targeted therapy. Using the model of PAL, he also brought original prospects on fundamental cellular biology such post translational modification of proteins (sumoylation, ubiquitinylation …).