Principal Investigator

Prof. Dr. Barbara M. Grüner

Department of Medical Oncology
University Hospital Essen

Prof. Dr. Barbara M. Grüner

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Summary

Tumor heterogeneity is one of the most prominent reasons responsible for resistance to (radio-)-therapy, tumor recurrence and metastatic cancer spread. Particularly non-small cell lung cancer (NSCLC) is associated with a high degree of inter- and intratumor heterogeneity associated with distinct mechanisms of origin including genetic, epigenetic and non-genetic sources. Using murine and human cell line models and patient-derived cell samples combined with powerful DNA-Barcoding technology, we will a) evaluate the impact of tumor heterogeneity on radiation response and resistance, b) determine if resistance to radiation therapy is clonal and, if so, acquired or inherent, c) deconvolute the similarities and differences of radiation response between primary lung tumors and metastases, and d) uncover the cellular mechanisms that drive radiation response and resistance in a heterogenous primary cancer cell population.
 

Dorsch M, Kowalczyk M, Planque M, Heilmann G, Urban S, Dujardin P, Forster J, Ueffing K, Nothdurft S, Oeck S, Paul A, Liffers ST, Kaschani F, Kaiser M, Schramm A, Siveke JT, Winslow MM, Fendt SM, Nalbant P, Grüner BM. Statins affect cancer cell plasticity with distinct consequences for tumor progression and metastasis. Cell Rep. 2021 Nov 23;37(8):110056.

Dujardin P., Baginska AK, Urban S, Grüner BM. Unraveling Tumor Heterogeneity by Using DNA Barcoding Technologies to Develop Personalized Treatment Strategies in Advanced-Stage PDAC. Cancers 2021 Aug 20;13(16):4187

Chuang CH, Dorsch M, Dujardin P, Silas S, Ueffing K, Hölken JM, Yang D, Winslow MM, Grüner BM. Altered mitochondria functionality defines a metastatic cell state in lung cancer and creates an exploitable vulnerability Cancer Research 2020 Nov 25;canres.1865.2020

Chuang CH, Greenside PG, Rogers ZN, Brady JJ, Yang D, Ma RK, Caswell DR, Chiou SH, Winters AF, Grüner BM, Ramaswami G, Spencley AL, Kopecky KE, Sayles LC, Sweet-Cordero EA, Li JB, Kundaje A, Winslow MM. Molecular definition of a metastatic lung cancer state reveals a targetable CD109-Janus kinase-Stat axis Nat Medicine 2017 Mar;23(3):291-300

Grüner BM*, Schulze CJ*, Yang D, Ogasawara D, Dix MM, McFarland CD, Chuang CH, Rogers ZN, Brown JM, Cravatt BF, Bogyo M, Winslow MM. An in vivo multiplexed small molecule screening platform to identify inhibitors of metastatic seeding Nature Methods 2016 Oct 13(10):883-9