Group Clotilde Wiel
Short description
Research on lung cancer metastasis, to determine how age and redox metabolism impact the metastatic process.
Research summary
Our overall goal is to define how age and redox-related changes in cancer support the metastatic dissemination of tumour cells.
Lung cancer is the deadliest cancer worldwide, primarily because it is often diagnosed late, when metastases have already formed. Importantly, the risk of developing a metastatic disease is two-fold higher in cancer patients above 60 years old compared to younger patients, independently of tumor grade. Efforts to identify metastasis driver mutations have been largely unsuccessful. Instead, many studies show that cancer cells metastasize by adapting to oxidative stress and rewiring metabolic pathways. During metastatic dissemination, cancer cells are exposed to heterogenous microenvironments and stresses, including oxidative stress
To understand how oxidative stress or age shape the cross-talk between cancer cells and the metastatic niche to support their dissemination, our research employs in vitro and in vivo CRISPR/Cas9 screens, single cell sequencing and metabolomics.
Research tools and resources
Our research involves several mouse models of lung cancer and metastasis.
We also use a wide range of cellular and molecular biology methods such as cancer cell lines, reporter cell lines, biosensors, ChIP, qPCR, WB, IF/IHC, microscopy, migration and invasion assays, among many others.
Our lab, together with Sayin lab (SCCR, GU) has developed lentiviral-CRISPR/Cas9 strategies to inactivate any gene-of-interest at tumor onset or later during tumor progression and metastasis.
Current group members
Clotilde Wiel, PhD, Principal investigator (Junior PI)
Dorota Raj, PhD, Postdoc
Kevin Ali, MSc, PhD student
Moa Beischer, Clinical research fellow
Selected publications
- Ageing promotes metastasis via activation of the integrated stress response.
Patel AAH, Dzanan JJ, Ali KX, Eklund EA, Alvarez SW, Raj D, Dankis M, Altinönder I, Schwarz M, Le Gal K, Bedel E, El Zowalaty AE, Jonasson E, Albatrok H, Gul N, Bossowski JP, Pillai R, Micke P, Botling J, Akyürek LM, Angeletti D, Sayin SI, Härtlova A, Papagiannakopoulos T, Olofsson Bagge R, Ståhlberg A, Hallqvist A, Wiel C, Sayin VI*. Nature. 2026 Apr;652(8112):1339-1348. *Co-corresponding author.
- Development of a high-throughput screening platform for identification of functional BACH1 inhibitors reveals compounds with anti-invasive potential.
Ali KX, Klenja-Skudrinja D, Higgins M, Walker D, Sharaf Y, Dankis M, Patel AAH, Raj D, Dzanan JJ, Svenningsen EB, Langlands A, Poulsen T, Honda T, Dinkova-Kostova AT, Wiel C*, Sayin VI, de la Vega L*. Redox Biol. 2026 Jul;94:104187. *Co-corresponding author.
- Amino acid restriction sensitizes lung cancer cells to ferroptosis via GCN2-dependent activation of the integrated stress response.
Garellick VA, Gul N, Horrieh P, Mustafa D, Patel AAH, Dankis M, Alvarez SW, Berndtson J, Mahdavi S, Schwarz M, Persson A, Zahirovic F, Wiel C, Sayin VI, Lindahl P. Redox Biol. 2026 Mar;90:103988.
- NRF2 activation by myeloid cell-derived oxidative stress induces SNAI-driven features of EMT in breast cancer.
Kaya M, Johnsson O, Issdisai N, Paul S, Wiel C, Dongre A, Hellstrand K, Martner A. Proc Natl Acad Sci U S A. 2026 May 26;123(21):e2521491123.
- Monotherapy With Immune Checkpoint Blockade Improves Survival Outcomes in KRAS-Mutant but Not KRAS Wild-Type Metastatic Lung Adenocarcinoma: Validation From an Extended Swedish Cohort.
Eklund EA, Sayin SI, Jonsson JS, van Renswoude H, Nyman J, Hallqvist A, Wiel C*, Sayin VI*. JTO Clin Res Rep. 2025 Jul 17;6(10):100880. *Co-corresponding author.
- Distinct metastatic organotropism shapes prognosis in lung adenocarcinoma with brain metastasis.
Sayin SI, Eklund EA, Ali KX, Dzanan JJ, Xylander M, Dankis M, Lindahl P, Sayin VI, Hallqvist A, Wiel C. Front Oncol. 2025 Apr 4;15:1569517.
- Targeting RAS-converting enzyme 1 overcomes senescence and improves progeria-like phenotypes of ZMPSTE24 deficiency.
Yao H, Chen X, Kashif M, Wang T, Ibrahim MX, Tüksammel E, Revêchon G, Eriksson M, Wiel C*, Bergo MO*. Aging Cell. 2020 Aug;19(8):e13200. *Co-corresponding author.
- The JAK1/2 inhibitor ruxolitinib delays premature aging phenotypes.
Griveau A*, Wiel C*, Ziegler DV, Bergo MO, Bernard D (2020) Aging Cell. 19: e13122. *co-first author.
- BACH1 Stabilization by Antioxidants Stimulates Lung Cancer Metastasis.
Wiel C, Le Gal K, Ibrahim MX, Jahangir CA, Kashif M, Yao H, Ziegler DV, Xu X, Ghosh T, Mondal T, Kanduri C, Lindahl P, Sayin VI, Bergo MO. Cell. 2019 Jul 11;178(2):330-345.e22.
