Research in the Thévenin Lab lies at the intersection of chemistry, biophysics, and cell biology, with a specific emphasis on membrane protein cell signaling, protein-membrane interactions, and innovative cancer drug delivery strategies. Our group has established itself at the forefront of developing pH-sensitive peptides as targeted cancer therapies, particularly utilizing the pH (Low) Insertion Peptide (pHLIP) platform. Significant accomplishments include pioneering the application of pHLIP peptides to deliver therapeutic agents such as microtubule inhibitors, receptor-targeted peptides, and mitochondrial-disrupting agents selectively into tumor cells. Our research has also provided fundamental insights into the molecular determinants of pHLIP’s tumor selectivity, notably lipid composition and divalent cation influence.
Currently, we are advancing our therapeutic platforms through several ongoing projects. These include re-engaging the immune response to attack tumors using innovative peptide-based conjugates, enhancing therapeutic targeting through rational peptide design guided by machine learning, and expanding translational validation efforts into preclinical models. Concurrently, we are leveraging systems biology to understand better the effects of transmembrane (TM) domain-targeting peptides and mutations in Receptor Protein-Tyrosine Phosphatases (RPTPs), particularly PTPRJ, on cancer signaling pathways and cellular behaviors. Additionally, we are actively exploring structural dynamics of RPTP oligomerization and interactions within membranes through collaborations employing high-resolution NMR and cryo-electron microscopy.
Looking ahead, my group aims to bridge our therapeutic strategies from bench to bedside by translating these membrane-targeted platforms into clinical applications. We will further integrate mechanistic insights with advanced computational approaches, such as systems biology analyses and peptide design driven by generative diffusion models, to refine our understanding of fundamental biology and personalize therapeutic interventions.