Our group is dedicated to translating aging research into oncology practice. We serve cancer patients, elderly individuals at risk of developing cancer, and cancer survivors facing accelerated health decline. We achieve this by developing innovative technologies and therapeutics capable of exposing and targeting age-related alterations in the metabolism of iron and other metals within the tissue microenvironment, recognized as drivers of malignancies.
Tumorigenesis in the Metabolically Aged Tissue Microenvironment
The accumulation of mutations is not the only connection between aging and cancer. Mounting evidence indicates that the aging tissue microenvironment actively selects and promotes the progression of mutant cells towards malignancies. We hypothesize that age-related metabolic changes play a key role in this process. Building on our recent findings (Maus et al. Nature Metabolism, 2023), we investigate how disrupted iron metabolism in the aged tissue microenvironment promotes inflammation, and micronutrient shortages, subsequently diverting the differentiation trajectory and fitness landscape of precancerous cells in the bone marrow and colon towards malignancy. Our goal is to develop methods that can non-invasively locate high-risk sites for cancer development, and therapeutics that can rejuvenate the tissue microenvironment thereby combating cancer.
The Metabolic Aging of Anti-Tumor Immunity
The decline in anti-tumor immunity with aging is speculated to be a significant factor contributing to the high incidence of cancer in elderly individuals. Leveraging our expertise in studying immunometabolism (Vaeth* and Maus* et al. Immunity, 2017), and the metabolism of aging (Maus et al. Nature Metabolism, 2023), our research in this area focuses on investigating how age-related disruption in iron metabolism is associated with decreased tumor surveillance and T cell exhaustion. Our objective is to identify approaches capable of rejuvenating the metabolic microenvironment where tumor surveillance and anti-tumor immunity occur, to thereby prevent and treat cancer.
The Metabolism of Cancer Survivorship
As advances in oncology contribute to a growing number of cancer survivors, the darker side of cancer therapies is becoming increasingly clear. Cancer survivors experience shortened life expectancy and suffer from inflammatory and fibrotic diseases at much higher rates compared to the general population. Our recent discoveries (Maus et al. Nature Metabolism, 2023) suggest a possible link between the adverse effects of cytotoxic therapies and iron accumulation. In this project, our goal is to shed light on how cancer therapy disrupts systemic and cellular iron homeostasis, how this is linked to cellular senescence, fibrosis and accelerated aging in individuals who underwent cytotoxic therapies. Our aim is to deliver novel diagnostics and therapeutics that can improve the lives of cancer survivors.
Group Leader
Mate Maus
Lab Manager
Claudia Gutiérrez Chávez
PhD Student
Francesca Cogo
Marc Guasch
Ning Huang
Master's student
Britt Van Voskuijlen
“My Bibliography” at the NCBI
- Maus M, López-Polo V, Mateo L, Lafarga M, Aguilera M, De Lama E, Meyer K, Sola A, Lopez-Martinez C, López-Alonso I, Guasch-Piqueras M, Hernandez-Gonzalez F, Chaib S, Rovira M, Sanchez M, Faner R, Agusti A, Diéguez-Hurtado R, Ortega S, Manonelles A, Engelhardt S, Monteiro F, Stephan-Otto Attolini C, Prats N, Albaiceta G, Cruzado JM, Serrano M. Iron accumulation drives fibrosis, senescence and the senescence-associated secretory phenotype. Nat Metab. 2023 Dec;5(12):2111-2130.
- Maus M, López-Polo V, Lafarga M, Aguilera M, De Lama E, Meyer K, Manonelles A, Sola A, Lopez Martinez C, López-Alonso I, Hernandez-Gonzales F, Chaib S, Rovira M, Sanchez M, Faner R, Agusti A, Prats N, Albaiceta G, Cruzado JM, Serrano M. Iron accumulation drives fibrosis, senescence, and the senescence-associated secretory phenotype. bioRxiv 2022 https://doi.org/10.1101/2022.07.29.501953
- Rovira M, […], Maus M, […], Serrano M. (2022) The lysosomal proteome of senescent cells contributes to the senescence secretome. Aging Cell. 2022 Oct;21(10):e13707
- Maus M, Serrano M. A novel redox cycle diverts cells from oncogene-induced senescence into cancer. Mol Cell. 2021 Sep 16;81(18):3672-3674.
- Kahlfuss S, Kaufmann U, Concepcion AR, Noyer L, Raphael D, Vaeth M, Yang J, Pancholi P, Maus M, Muller J, Kozhaya L, Khodadadi-Jamayran A, Sun Z, Shaw P, Unutmaz D, Stathopulos PB, Feist C, Cameron SB, Turvey SE, Feske S. STIM1-mediated calcium influx controls antifungal immunity and the metabolic function of non-pathogenic Th17 cells. EMBO Mol Med. 2020 Aug 7;12(8):e11592.
- Saint Fleur-Lominy S* and Maus M*, Vaeth M, Lange I, Zee I, Suh D, Liu C, Wu X, Tikhonova A, Aifantis I, Feske S. STIM1 and STIM2 Mediate Cancer-Induced Inflammation in T Cell Acute Lymphoblastic Leukemia. Cell Rep. 2018 Sep 11;24(11):3045-3060.e5. (*equal contribution)
- Vaeth M* and Maus M*, Klein-Hessling S, Freinkman E, Yang J, Eckstein M, Cameron S, Turvey SE, Serfling E, Berberich-Siebelt F, Possemato R, Feske S. Store-Operated Ca2+ Entry Controls Clonal Expansion of T Cells through Metabolic Reprogramming. Immunity. 2017 Oct 17;47(4):664-679.e6. (*equal contribution)
- Maus M, Cuk M, Patel B, Lian J, Ouimet M, Kaufmann U, Yang J, Horvath R, Hornig-Do HT, Chrzanowska-Lightowlers ZM, Moore KJ, Cuervo AM, Feske S. Store-Operated Ca2+ Entry Controls Induction of Lipolysis and the Transcriptional Reprogramming to Lipid Metabolism. Cell Metab. 2017 Mar 7;25(3):698-712.
- Vaeth M, Zee I, Concepcion AR, Maus M, Shaw P, Portal-Celhay C, Zahra A, Kozhaya L, Weidinger C, Philips J, Unutmaz D, Feske S. Ca2+ Signaling but Not Store-Operated Ca2+ Entry Is Required for the Function of Macrophages and Dendritic Cells. J Immunol. 2015 Aug 1;195(3):1202-17.
- Maus M, Jairaman A, Stathopulos PB, Muik M, Fahrner M, Weidinger C, Benson M, Fuchs S, Ehl S, Romanin C, Ikura M, Prakriya M, Feske S. Missense mutation in immunodeficient patients shows the multifunctional roles of coiled-coil domain 3 (CC3) in STIM1 activation. Proc Natl Acad Sci U S A. 2015 May 12;112(19):6206-11.
- Maus M, Medgyesi D, Kiss E, Schneider AE, Enyedi A, Szilágyi N, Matkó J, Sármay G. B cell receptor-induced Ca2+ mobilization mediates F-actin rearrangements and is indispensable for adhesion and spreading of B lymphocytes. J Leukoc Biol. 2013 Apr;93(4):537-47.
- Maus M, Medgyesi D, Kövesdi D, Csuka D, Koncz G, Sármay G. Grb2 associated binder 2 couples B-cell receptor to cell survival. Cell Signal. 2009 Feb;21(2):220-7.
- Sármay G, Angyal A, Kertész A, Maus M, Medgyesi D. The multiple function of Grb2 associated binder (Gab) adaptor/scaffolding protein in immune cell signaling. Immunol Lett. 2006 Apr 15;104(1-2):76-82.
Title: Understanding and translating the connection between age-associated iron dyshomeostasis and myeloproliferative neoplasms in the elderly (MYELOIRONAGE). Funding entity: Agencia Estatal de Investigación – Ministerio de Ciencia e Innovación. Ref: PID2022-142205OB-I00. Duration: 01/09/2023 – 31/08/2027. PI: Mate Maus.
This group is supported by CaixaResearch and Ayudas para contratos Ramón y Cajal (RYC) (REF: RYC2020-030652-I)
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