Immunosenscence and stem cell metabolism

We are focused on identifying the metabolic pathways regulating hematopoietic stem and immune cells function. Our goal is to develop targeted metabolic therapies capable of preserving hematopoietic stem and immune cell functions in the context of aging and chemotherapeutic treatments.

Metabolic reprogramming of aged hematopoetic stem and immune cells

Aging is associated with the decline of immune function, especially T-cell mediated activity, which contributes to a reduced tumor immunosurveillance and thus increased tumor insurgences with age. Lymphoid progenitor cells are formed in the bone marrow from hematopoietic stem cells (HSCs) and aging processes profoundly perturb HSCs function. Aging primes HSCs toward myeloid lineages and thus reduces the lymphoid compartment and compromises immune-reconstitution and immunosurveillance.

Over the past years, metabolism has been emerging as major regulator of stem and immune cells function and activation. Recently, it has been shown that metabolic interventions both in animal model and in human can profoundly alter stem and immune cell function. In light of this, we are interested in identifying the metabolic changes happening in HSCs and immune system during aging and developping targeted metabolic therapies in order to re-program stem and immune function in the elderly. 

Metabolic prevention of chemotherapy-induced immunosuppression

Chemotherapy results in substantial damage to the immune system by affecting the hematopoietic stem and progenitor cells (HSPCs) function, leading to myeloid bias differentiation and subsequent immunosuppression. We are interested in understanding the metabolic changes occuring upon chemotherapy in HSPCs and T cells and developping metabolic/nutritional strategies capable of preserving stem and immune cell functions. 

NAD metabolism in immune cells

NAD precursor nicotinamide riboside (NR) has been shown to protect against high fat diet-induced obesity and extend lifespan. Interestingly, in our previous studies we demonstrated that NR is capable to expand HSPCs and lymphoid compartments in vivo  (Vannini et al., Under revision) Following up this earlier research, our goal now is to understand the role of NAD metabolism in immune cells.  

• Girotra M, Thierry AC, Harari A, Coukos G, Naveiras O, Vannini N. Measurement of mitochondrial mass and membrane potential in hematopoietic stem cell and T-cell by flow cytometry. J Vis Exp In Press

• Vannini N, Campos V, Girotra M, Trachsel V, Rojas-Sutterlin S, Tratwal J, Ragusa S, Stefanidis E, Ryu D, Rainer PY, Nikitin G, Giger S, Li TY, Semilietof A, Oggier A, Yersin Y, Tauzin L, Pirinen E, Cheng WC, Ratajczak J, Canto C, Ehrbar M, Sizzano F, Petrova TV, Vanhecke D, Zhang L, Romero P, Nahimana A, Cherix S, Duchosal MA, Ho PC, Deplancke B, Coukos G, Auwerx J, Lutolf MP, Naveiras O*. The NAD-Booster Nicotinamide Riboside Potently Stimulates Hematopoiesis through Increased Mitochondrial Clearance. Cell Stem Cell. 2019

• Roch A, Giger S, Girotra M, Campos V, Vannini N, Naveiras O, Gobaa S, Lutolf MP. Identification of functional artificial niches by single hematopoietic stem cell fate analyses. Nat Commun. 2017

• Vannini N, Girotra M, Naveiras O, Nikitin G, Campos V, Giger S, Roch A, Auwerx J, Lutolf MP. Specification of haematopoietic stem cell fate via modulation of mitochondrial activity. Nat Commun. 2016 

• Vannini N, Roch A, Naveiras O, Griffa A, Kobel S, Lutolf MP. Identification of in vitro HSC fate regulators by differential lipid raft clustering. Cell Cycle. 2012

• Kristian Gerhard Jebsen Foundation
• Nestlé Institute of Health Science