Le laboratoire des IMRCP est une unité étudiant l’organisation de molécules (tensioactifs, lipides…), de nanoparticules (organiques ou inorganique) et de polymères (naturels ou non), en solution mais aussi en masse.

Cette organisation est responsable de multiples propriétés et applications tant en biologie et médecine (agents de contraste, transport et relargages de composés bioactifs, matériaux biocompatibles…), qu’en science des matériaux (capteurs, aéronautique…), ou en environnement (procédés verts, analyse de polluants…).

Leurs compétences larges qui vont de la synthèse de ces molécules ou polymères à la caractérisation de ces organisations et propriétés permettent au laboratoire de répondre à de nombreux questionnements scientifiques dans des thématiques extrêmement variées.

Ainsi, depuis de nombreuses années, leurs collaborations en pharmacologie, biologie et médecine ont été extrêmement fructueuses et enrichissantes. Favoriser de nouveaux liens et travaux dans ces domaines est une priorité du laboratoire.

To improve their adaptation to the changing environment presents on Earth, organisms from bacteria to mammals have evolved a timing system that anticipates these changes. This endogenous timing system, called the circadian clock, orchestrates most aspects of physiology and behavior. The mammalian circadian clock is hierarchically organized.

A central clock localized in the Suprachiasmatic Nucleus (SCN) of the hypothalamus is daily synchronized by the light via the retina-hypothalamus tract and coordinates the peripheral clocks localized in peripheral tissues. The SCN synchronizes most aspects of circadian physiology throughout the life and is required to keep phase coherence between the different peripheral organs.

While new data shows that this circadian clock is disrupted in many human pathologies and during aging, the impact of this disruption on these conditions is it still unclear.

Relapses caused by drug resistance is the major barrier for effective treatment of most solid tumors and hematological malignancies. In acute myeloid leukemia (AML), we showed that mitochondrial adaptation is a critical determinant of resistance to cytarabine (AraC).

We proved that this is associated with an increased availability of respiratory substrates and cofactors, mitochondrial biogenesis and transfer from stromal cells, iron-sulfur cluster biogenesis, BCL2 dependency, and ROS detoxification upon inflammatory and stress responses.

We next demonstrated that the ectonucleotidase CD39 and extracellular ATP promote AraC resistance by enhancing mitochondrial biogenesis and OxPHOS activity through the activation of a cAMP-/ATF4-mediated mitochondrial stress response (MSR). Interestingly, OxPHOS metabolism and MSR are also determinants of the response to IDH- and BCL2-selective inhibitors.

Additionally, our group and others have identified several other markers of relapse-initiating cells (RICs) that are metabolite sensors or transporters such as CD36, SLC7A5 and SLC1A3, which underlined metabolic dialogues between resistant blasts and their microenvironment. This provided access to a broad range of respiratory substrates including fatty acids, glutamine, aspartate, lactate and/or glucose to support the energetic metabolism of RICs. More specifically,

CD36 was positively associated with extramedullary dissemination of leukemic blasts in vivo and in patients. Furthermore, CD36 inhibition reduced metastasis of blasts and prolonged survival of chemotherapy-treated mice. Our ongoing work is highlighting that the role of metabolic and transcriptional trajectories of three distinct RIC populations, diverse tissue metabolomic ecosystems and the impact of ketogenic diet during the course of disease progression.