Federico Pietrocola's group

In the lab, we investigate how cellular responses to stress (e.g., autophagy, senescence) contribute to organismal ageing and age-associated pathologies.

The long-term goal of our research is to implement lifestyle/pharmacological interventions to slow down the ageing process and improve ageing-related phenotypes (e.g., regeneration after injury, chronic inflammation, systemic metabolic alterations).

We currently have three ongoing projects:

  • To develop anti-senescence immunotherapies: We aim to unravel the immunological mechanisms that enable senescent cells to escape immune clearance and accumulate in tissues during ageing, tissue fibrosis and neoplastic transformation. We endeavour to identify ‘druggable’ Senescence Associated Immune Checkpoints (SAICs) molecules to trigger the immune system-mediated elimination of senescent cells.
     
  • To identify metabolic vulnerabilities of senescent cells: We use bulk and single cells metabolomics to define perturbations in metabolic networks that specifically define the senescent state. We are currently focusing on the role of polyamines metabolism in the regulation of the senescent phenotype.
     
  • To discover pharmacological agents able to target multiple hallmarks of ageing:  We deploy high-content fluorescence microscopy to identify food-derived compounds endowed with the capacity to (i) improve cellular proteostasis, (ii) boost mitochondrial function, (iii) limit chronic inflammation, and (iv) selectively kill senescent cells.

Lab Members

Federico Pietrocola

Group leader and Assistant Professor

I obtained my PhD Degree in Cellular and Molecular Biology (Paris XI University, France) in 2015. After a two-years postdoc in Guido Kroemer’s lab (Cordeliers Research Institute, Paris, France), I joined the laboratory of Manuel Serrano under a prestigious EMBO Long-Term Postdoctoral Fellowship. In 2020, I have started my independent research career at Karolinska Institutet, Department of Biosciences and Nutrition.

Francesca Castoldi

Postdoc

I obtained my PhD degree in Cellular and Molecular Biology in 2018 (Paris-Saclay University, France) in the laboratory of Guido Kroemer. In 2021, I joined the Pietrocola’s lab as a postdoc. In the lab, I study (i) the immunological mechanisms that allow senescent cells to accumulate in damaged tissues; and (ii) the effect of genetic/pharmacological targeting of polyamines metabolism in the regulation of senescence. I currently receive support from the Eva & Alex Wallström Foundation, the Blanceflor Foundation and SSMF Post-doctoral Grant.

Chiara Annunziata

Postdoc

I obtained my PhD in Pharmacology in 2020 (University of Naples Federico II, Italy) in the laboratory of Rosaria Meli. In 2021, I joined the Pietrocola’s lab as a postdoc under a competitive STAR Program Fellowship. In the lab, I am specifically interested in identifying food-derived compounds that improve multiple aspects of cellular ageing. Furthermore, I am investigating the role of senescent cells in the stromal compartment of lung cancer.

Yvonne Giannoula

MSc student

Selected publications

  1. Induction of senescence renders cancer cells highly immunogenic.
    Marin I, Boix O, García A, Sirois I, Caballe A, Zarzuela E, Ruano I, Stephan-Otto Attolini C, Prats N, López-Domínguez JA, Kovatcheva M, Garralda E, Muñoz J, Caron E, Abad M, Gros A, Pietrocola F,* Manuel Serrano.*
    bioRxiv. 2022 June 06
     
  2. Natural killer cells act as an extrinsic barrier for in vivo reprogramming.
    Melendez E, Chondronasiou D, Mosteiro L, Martínez de Villarreal J, Fernández-Alfara M, Lynch CJ, Grimm D, Real FX, Alcamí J, Climent N, Pietrocola F, Serrano M
    Development 2022 Apr;149(8):
     
  3. Autophagy in major human diseases.
    Klionsky DJ, Petroni G, Amaravadi RK, Baehrecke EH, Ballabio A, Boya P, Bravo-San Pedro JM, Cadwell K, Cecconi F, Choi AMK, Choi ME, Chu CT, Codogno P, Colombo MI, Cuervo AM, Deretic V, Dikic I, Elazar Z, Eskelinen EL, Fimia GM, Gewirtz DA, Green DR, Hansen M, Jäättelä M, Johansen T, Juhász G, Karantza V, Kraft C, Kroemer G, Ktistakis NT, Kumar S, Lopez-Otin C, Macleod KF, Madeo F, Martinez J, Meléndez A, Mizushima N, Münz C, Penninger JM, Perera RM, Piacentini M, Reggiori F, Rubinsztein DC, Ryan KM, Sadoshima J, Santambrogio L, Scorrano L, Simon HU, Simon AK, Simonsen A, Stolz A, Tavernarakis N, Tooze SA, Yoshimori T, Yuan J, Yue Z, Zhong Q, Galluzzi L, Pietrocola F
    EMBO J 2021 10;40(19):e108863
     
  4. Autophagy-mediated metabolic effects of aspirin.
    Castoldi F, Humeau J, Martins I, Lachkar S, Loew D, Dingli F, Durand S, Enot D, Bossut N, Chery A, Aprahamian F, Demont Y, Opolon P, Signolle N, Sauvat A, Semeraro M, Bezu L, Baracco EE, Vacchelli E, Pol JG, Lévesque S, Bloy N, Sica V, Maiuri MC, Kroemer G, Pietrocola F
    Cell Death Discov 2020 Nov;6(1):129
     
  5. Autophagy in the cancer-immunity dialogue.
    Yamazaki T, Bravo-San Pedro JM, Galluzzi L, Kroemer G, Pietrocola F
    Adv Drug Deliv Rev 2021 02;169():40-50
     
  6. Chemical activation of SAT1 corrects diet-induced metabolic syndrome.
    Castoldi F, Hyvönen MT, Durand S, Aprahamian F, Sauvat A, Malik SA, Baracco EE, Vacchelli E, Opolon P, Signolle N, Lefevre D, Bossut N, Eisenberg T, Dammbrueck C, Pendl T, Kremer M, Lachkar S, Einer C, Michalke B, Zischka H, Madeo F, Keinänen TA, Maiuri MC, Pietrocola F, Kroemer G
    Cell Death Differ 2020 10;27(10):2904-2920
     
  7. Identification and characterization of Cardiac Glycosides as senolytic compounds.
    Triana-Martínez F, Picallos-Rabina P, Da Silva-Álvarez S, Pietrocola F, Llanos S, Rodilla V, et al
    Nat Commun 2019 10;10(1):4731

     
  8. Lysosomal trapping of palbociclib and its functional implications.
    Llanos S, Megias D, Blanco-Aparicio C, Hernández-Encinas E, Rovira M, Pietrocola F, et al
    Oncogene 2019 05;38(20):3886-3902

     
  9. Aspirin Recapitulates Features of Caloric Restriction.
    Pietrocola F, Castoldi F, Markaki M, Lachkar S, Chen G, Enot DP, et al
    Cell Rep 2018 02;22(9):2395-2407

     
  10. Spermidine in health and disease.
    Madeo F, Eisenberg T, Pietrocola F, Kroemer G
    Science 2018 Jan;359(6374):
     
  11. Nutrition, inflammation and cancer.
    Zitvogel L, Pietrocola F, Kroemer G
    Nat. Immunol. 2017 Jul;18(8):843-850
     
  12. Metabolic effects of fasting on human and mouse blood in vivo.
    Pietrocola F, Demont Y, Castoldi F, Enot D, Durand S, Semeraro M, et al
    Autophagy 2017 Mar;13(3):567-578

     
  13. Caloric Restriction Mimetics Enhance Anticancer Immunosurveillance.
    Pietrocola F, Pol J, Vacchelli E, Rao S, Enot DP, Baracco EE, et al
    Cancer Cell 2016 07;30(1):147-160

     
  14. Acetyl coenzyme A: a central metabolite and second messenger.
    Pietrocola F, Galluzzi L, Bravo-San Pedro JM, Madeo F, Kroemer G
    Cell Metab. 2015 Jun;21(6):805-21
     
  15. Caloric restriction mimetics: towards a molecular definition.
    Madeo F, Pietrocola F, Eisenberg T, Kroemer G
    Nat Rev Drug Discov 2014 10;13(10):727-40