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 connection between aging and cancer extends beyond the accumulation of mutations. Mounting evidence suggests that the aging tissue microenvironment actively selects and promotes the progression of mutant cells toward malignancy. Building on our experience in exploring the interplay between inflammation and tumorigenesis (Saint-Fleur* and Maus* et al. Cell Rep. 2018), and our recent findings (Maus* and López-Polo* Nat Metab. 2023), we investigate how renewing tissues adapt to age-related disruption in iron metabolism and how this adaptation contributes to alterations in the differentiation trajectory and fitness landscape of precancerous cells in both bone marrow and the colon, pushing them toward malignancy. Our goal is to develop non-invasive methods capable of identifying high-risk sites for cancer development by imaging disruption in iron metabolism. Additionally, we aim to devise therapeutic strategies that can rejuvenate the tissue microenvironment by restoring iron metabolism, thereby offering a promising approach to treat cancer.
The Metabolism of Cancer Survivorship. As advances in oncology lead to a growing population of cancer survivors, the downsides of cancer therapies are becoming increasingly apparent. Cancer survivors not only face a shortened life expectancy but also grapple with higher rates of inflammatory and fibrotic diseases compared to the general population. Drawing on our experience in studying metabolism (Maus et al. Cell Metab. 2017) and our recent findings (Maus et al. Nat Metab. 2023), our focus is on unraveling the link between the adverse effects of cytotoxic therapies and iron accumulation. In this research line, our goal is to shed light on how cancer therapy disrupts both systemic and cellular iron homeostasis, and understand the intricate links to cellular senescence, fibrosis and accelerated aging in individuals who have received treatment with cytotoxic therapies. Ultimately, our goal is to develop innovative diagnostics and therapeutics that can enhance the quality of life for cancer survivors.
The Metabolic Aging of Anti-Tumor Immunity. The decline in anti-tumor immunity in aging is recognized as a key contributor to the elevated incidence of cancer in the elderly. Leveraging our expertise in studying immunometabolism (Vaeth* and Maus* et al. Immunity. 2017), and the metabolism of aging (Maus et al. Nat Metab. 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 strategies that can rejuvenate the metabolic microenvironment, aiming to reinvigorate anti-tumor immunity.
*Equal contribution.
Group Leader
Mate Maus
PhD Student
Francesca Cogo
Marc Guasch
Ning Huang
“My Bibliography” at the NCBI
- Amengual J, Alay A, Vaquero J, Gonzalez-Sanchez E, Bertran E, Sánchez A, Herrera B, Meyer K, Maus M, Serrano M, Martínez-Chantar ML, Fabregat I. Iron chelation as a new therapeutic approach to prevent senescence and liver fibrosis progression. Cell Death Dis. 2024 Sep 17;15(9):680. doi: 10.1038/s41419-024-07063-0.
- López-Polo V, Maus M, Zacharioudakis E, Lafarga M, Attolini CS, Marques FDM, Kovatcheva M, Gavathiotis E, Serrano M. Release of mitochondrial dsRNA into the cytosol is a key driver of the inflammatory phenotype of senescent cells. Nat Commun. 2024 Aug 27;15(1):7378. doi: 10.1038/s41467-024-51363-0.
- 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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