Dr. Marco De Vivo, PhD | Principal Investigator and Associate Director, Italian Institute of Technology, IIT
Professor bio:
Dr. De Vivo is head of the Molecular Modeling and Drug Discovery laboratory at the Italian Institute of Technology (IIT). He is also the Associate Director of the IIT, responsible for Computational Sciences. He is the Director of the Italian CECAM-IT-SIMUL node of the CECAM (https://www.cecam.org) organization, which promotes advanced computational methods for essential problems in frontier areas of science and technology. The lab develops and applies computational methods to achieve an atomic-level comprehension of chemical systems. This information is used to design potent inhibitors and nanoparticles with programmed properties as a promising starting point for drug discovery programs. His research activity is partially supported by the Italian Association for Cancer Research (AIRC), where he is now a Member of the Technical Scientific Committee. In 2017, he received the Outstanding Junior Faculty Award from the American Chemical Society (ACS), Computers in Chemistry Division. He is a member of the Editorial Advisory Board of scientific journals like JCIM (ACS Publications) and Chem (Cell Press). In 2021, he co-founded IAMA Therapeutics, which develops new drugs for brain disorders. In 2023, he received the ESMEC International Alumni Award from the European School of Medicinal Chemistry. In 2024, he has been elected Vice President (Future President,
2026-2028) of the International Society of Quantum Biology and Pharmacology (ISQBP). He is a Board Member of the Pharmaceutical Chemistry Division of Società Chimica Italiana. He is the Executive Editor of the Journal of Chemical Theory and Computation (ACS publication), the reference journal for the broad community of computational chemists.
Abstract:
My lab develops and applies computational methods to investigate how pharmaceutically relevant (bio)chemical systems operate at the atomic level. We use these mechanistic insights to design and synthesize small molecules to initiate drug discovery efforts. With these premises, I will first describe our work on understanding the molecular mechanism of the Na–K–Cl cotransporter 1 (NKCC1), which regulates ion transport across cell membranes. Alterations in chloride concentrations in neurons are linked to neurological conditions, making NKCC1 inhibition a promising strategy for neuroscience drug discovery. By integrating molecular modeling and medicinal chemistry, we have identified a new class of small molecules specifically targeting NKCC1 to treat core symptoms of neurodevelopmental disorders. One of these molecules derived from this effort, IAMA-6, is now in Phase 1 clinical trials with Iama Therapeutics. Then, I will present our current efforts in designing RNA splicing modulators, which hold therapeutic potential for various congenital diseases and cancer. I will again start from mechanistic insights for splicing in group II introns and then move to the computer-aided structure-based design of potent RNA-targeted compounds. I will discuss how such novel compounds act at the core of the splicing catalytic site with an unprecedented mode of action. This is confirmed by multiple RNA-ligand X-ray complexes combined with free energy perturbation calculations.
