VANNINI Nicola
Professor
Immunosenescence and stem cell metabolism (Vannini Group)
In our group we are interested in identifying the metabolic pathways regulating hematopoietic stem and immune cell’s function. Our goal is to develop targeted metabolic therapies capable to preserve hematopoietic stem and immune cell functionalty in the context of aging and chemotherapeutic treatments.
METABOLIC REPROGRAMMING OF AGED HEMATOPOETIC STEM AND IMMUNE CELLS
As we age, our immune system gradually weakens, especially in T-cell activity, leading to reduced tumor surveillance and a higher risk of cancer. One key factor behind this decline lies in hematopoietic stem cells (HSCs), which generate all blood and immune cells in the bone marrow. Aging shifts HSCs toward producing more myeloid cells and fewer lymphoid cells, ultimately compromising immune balance and resilience.
In our lab, we are particularly interested in the role of metabolism in this process. Metabolic pathways are now recognized as central regulators of both stem cell behavior and immune cell activation. Excitingly, studies in both animal models and humans have shown that metabolic interventions can restore or reshape immune and stem cell function. Our research aims to uncover the metabolic changes that occur in HSCs and the immune system during aging, with the long-term goal of developing targeted therapies to “reprogram” immunity and improve health in the elderly.
METABOLIC PREVENTION OF CHEMOTHERAPY-INDUCED IMMUNOSUPPRESSION
Chemotherapy, while effective against cancer, often causes serious damage to the immune system. It disrupts the function of hematopoietic stem and progenitor cells (HSPCs), pushing them toward myeloid-biased differentiation and resulting in immunosuppression.
Our lab is investigating how chemotherapy reshapes the metabolism of HSPCs and T cells. By uncovering these metabolic changes, we aim to design metabolic and nutritional strategies that protect and preserve both stem cell and immune cell function during cancer treatment. Ultimately, our goal is to improve patient resilience and long-term recovery by maintaining a healthier immune system.
NAD METABOLISM IN IMMUNE CELLS
The NAD precursor nicotinamide riboside (NR) has been shown to protect against high-fat diet–induced obesity and extend lifespan. In our own studies, we discovered that NR can also expand hematopoietic stem and progenitor cells (HSPCs) and boost the lymphoid compartment in vivo.
Building on these findings, our current research focuses on unraveling the role of NAD metabolism in immune cells. By understanding how NAD pathways shape immune function, we aim to uncover new strategies to strengthen immunity and promote healthy aging.
Members
Publications
Age-associated nicotinamide adenine dinucleotide decline drives CAR-T cell failure
Helen Carrasco Hope, Jana de Sostoa, Pierpaolo Ginefra, Massimo Andreatta, Yi-Hsuan Chiang, Catherine Ronet, Christine Pich-Bavastro, Jesús Corria Osorio, François Kuonen, Johan Auwerx, Patrizia D’Amelio, Ping-Chih Ho, Santiago J. Carmona, George Coukos, Denis Migliorini, Nicola Vannini, Nature Cancer (2025)
| Journal article
Metabolic alterations in HSCs during aging and leukemogenesis
Yi-Hsuan Chiang, Stephan Emmrich, Nicola Vannini, Physiology (2025)
| Journal article
PGE2 inhibits TIL expansion by disrupting IL-2 signalling and mitochondrial function
Matteo Morotti, Alizee J. Grimm, Helen Carrasco Hope, Marion Arnaud, Mathieu Desbuisson, Nicolas Rayroux, David Barras, Maria Masid, Baptiste Murgues, Bovannak S. Chap, Marco Ongaro, Ioanna A. Rota, Catherine Ronet, Aspram Minasyan, Johanna Chiffelle, Sebastian B. Lacher, Sara Bobisse, Clément Murgues, Eleonora Ghisoni, Khaoula Ouchen, Ribal Bou Mjahed, Fabrizio Benedetti, Naoill Abdellaoui, Riccardo Turrini, Philippe O. Gannon, Khalil Zaman, Patrice Mathevet, Loic Lelievre, Isaac Crespo, Marcus Conrad, Gregory Verdeil, Lana E. Kandalaft, Julien Dagher, Jesus Corria-Osorio, Marie-Agnes Doucey, Ping-Chih Ho, Alexandre Harari, Nicola Vannini, Jan P. Böttcher, Denarda Dangaj Laniti, George Coukos, Nature (2024)
| Journal article
Urolithin-A promotes CD8+ T cell-mediated cancer immunosurveillance via FOXO1 activation.
Pierpaolo Ginefra, Helen Carrasco Hope, Yi-Hsuan Chiang, Sophie Nutten, Stephanie Blum, George Coukos, Nicola Vannini, Cancer Research Communications (2024)
| Journal article
Induction of mitochondrial recycling reverts age-associated decline of the hematopoietic and immune systems
Mukul Girotra and Yi-Hsuan Chiang and Melanie Charmoy and Pierpaolo Ginefra and Helen Carrasco Hope and Charles Bataclan and Yi-Ru Yu and Frederica Schyrr and Fabien Franco and Hartmut Geiger and Stephane Cherix and Ping-Chih Ho and Olaia Naveiras and Johan Auwerx and Werner Held and Nicola Vannini, Nature Aging (2023)
| Journal article
Disturbed mitochondrial dynamics in CD8+ TILs reinforce T cell exhaustion
Nature Immunology (2020)
| Journal article