The Kübler Lab is an interdisciplinary research group working at the interface of biology, computational biology, and medical oncology. The lab specializes in studying the molecular mechanisms and genomic changes that initiate and drive cancer development, using novel experimental and computational technologies. A better understanding of the key processes underlying cancer onset and progression will ultimately enable us to intervene at an early stage and prevent cancer, an approach instrumental in improving patient outcome.
Main research topics
Cancer is the result of clonal evolution, where genomic changes in normal cells can lead to the formation of early precancerous lesions. Additional accumulation of molecular alterations can then result in the development of invasive cancer. However, if detected and treated early, precancerous lesions can be cured before they progress to cancer.
The Kübler Lab is dedicated to investigating these genomic alterations and their impact on cancer development. We develop and apply innovative experimental multi-omics techniques to extract multiple types of molecular information from archived samples. These novel methods have the potential to unlock archives as a valuable resource for translational research, particularly in the study of uncommon cancers and early tumorigenesis.
The Kübler Lab also develops novel computational methods that predict the cell-of-origin of cancer and identifies the susceptibilities of individual cell types for cancer transformation. By combining our cutting-edge computational and experimental techniques, we can obtain a more comprehensive understanding of the molecular changes that are involved in the initiation, progression, and transformation of pre-malignant lesions to invasive cancer.
Our long-term vision is to improve precision medicine and to translate our findings to the clinic by innovating strategies for the prevention, early detection and treatment of cancer and its precursors.
AUGUST 2022, Science
Diverse mutational landscapes in human lymphocytes
Machado HE, Mitchell E*, Øbro NF*, Kübler K*, Davies M, Leongamornlert D, Cull A, Maura F, Sanders MA, Cagan ATJ, McDonald C, Belmonte M, Shepherd MS, Vieira Braga FA, Osborne RJ, Mahbubani K, Martincorena I, Laurenti E, Green AR, Getz G, Polak P, Saeb-Parsy K, Hodson DJ, Kent DG, Campbell PJ. Nature. Aug;608(7924):724-732. doi: 10.1038/s41586-022-05072-7 (*, contributed equally)
AUGUST 2019, Science
RNA sequence analysis reveals macroscopic somatic clonal expansion across normal tissues
Yizhak K, Aguet F, Kim J, Hess JM, Kübler K, Grimsby J, Frazer R, Zhang H, Haradhvala NJ, Rosebrock D, Livitz D, Li X, Arich-Landkof E, Shoresh N, Stewart C, Segrè AV, Branton PA, Polak P, Ardlie KG, Getz G. R 2019; 364: 6444. doi: 10.1126/science.aaw0726
JANUARY 2019, bioRxiv
Pan-Cancer Analysis of Whole Genomes Network.Tumor mutational landscape is a record of the pre-malignant state
Kübler K *, Karlić R* Haradhvala NJ, Ha K, Kim J, Kuzman M, Jiao W, Gakkhar S, Mouw KW, Braunstein LZ, Elemento O, Biankin AO, Rooman I, Miller M, Karthaus WR, Nogiec CD, Juvenson E, Curry E, Mino-Kenudson M, Ellisen LW, Brown R, Gusev A, Tomasetti C, Lolkema MP, Steeghs N, van Herpen C, Kim H-G, Lee H, VlahovicÃåek K, Bernstein BE, Sawyers CL, Hoadley KA, Cuppen E, Koren A, Arndt PF, Louis DN, Stein LD, Foulkes WD, Polak P, Getz G on behalf of the PCAWG Pathology and Clinical Correlates Working Group, and the ICGC/TCGA bioRxiv, doi: https://doi.org/10.1101/517565 (*, contributed equally),
AUGUST 2018, Cancer Cell
Widespread Chromosomal Losses and Mitochondrial DNA Alterations as Genetic Drivers in Hürthle Cell Carcinoma
Gopal RK*, Kübler K*, Calvo SE, Polak P, Livitz D, Rosebrock D, Sadow PM, Campbell B, Donovan SE, Amin S, Gigliotti BJ, Grabarek Z, Hess JM, Stewart C, Braunstein LZ, Arndt PF, Mordecai S, Shih AR, Chaves F, Zhan T, Lubitz CC, Kim J, Iafrate AJ, Wirth L, Parangi S, Leshchiner I, Daniels GH, Mootha VK, Dias-Santagata D, Getz G, McFadden DG.
AUGUST 2017, Nature Genetics
A mutational signature reveals alterations underlying deficient homologous recombination repair in breast cancer
Polak P, Kim J, Braunstein LZ, Karlic R, Haradhavala NJ, Tiao G, Rosebrock D, Livitz D, Kübler K, Mouw KW, Kamburov A, Maruvka YE, Leshchiner I, Lander ES, Golub TR, Zick A, Orthwein A, Lawrence MS, Batra RN, Caldas C, Haber DA, Laird PW, Shen H, Ellisen LW, D’Andrea AD, Chanock SJ, Foulkes WD, Getz. Nature Genetics;49(10):1476-1486 doi: 10.1038/ng.3934.
Overcoming therapeutic barriers through cooperation
Our PhD student Claudia was admitted to the Berlin School of Integrative Oncology, the joint graduate school of the Charité, Humboldt University, Free University and non-university research institutions, where talented students investigate the most demanding problems in clinical oncology in an inter-transdisciplinary, international and cooperative environment.
Collaborations and Fellowships
To get trained in the bioinformatic analysis of genomic data from the best in the field, our research fellow Leonie spent the last 6 months of 2023 at Harvard Medical School as well as the Memorial Sloan Kettering Cancer Center, and had her endeavors founded by a Charité Ingeborg Rapoport Fellowship and a Short-Term Fellowship by the Deutsche Krebshilfe.
More women in STEM: Johnson & Johnson WiSTEM2D Award
Congratulations to our research assistant Ali, who was among a handful of female students selected across all disciplines at her alma mater, the University College Cork, to receive the Johnson & Johnson WiSTEM2D Scholarship Award for the Academic Year 2023/24!
Happy Holidays from the Kübler Lab
The Kübler Lab wishes a joyful holiday season! May the coming year be filled with exciting discoveries, happiness, and continued success – cheers to a wonderful 2024!
Auf die Erdbeeren, fertig, los: Am #Girlsday konnten Schülerinnen gemeinsam mit Staatssekretärin Judith Pirscher die DNA aus Erdbeeren extrahieren.
„Wir fördern Talente und keine Klischees. In der Wissenschaft brauchen wir viele Perspektiven und die Kreativität aller. Komm zu uns und lass deinen Traum mit uns zusammen wahrwerden.“
In ihrer wissenschaftlichen Arbeit widmet sich Kirsten Kübler daher der Aufgabe, auch für andere Krebsarten Möglichkeiten der Früherkennung und Prävention zu finden.
Prof. Kirsten Kübler is a clinician scientist, and her expertise in clinical oncology is complemented by her experience in tumor genomics using both experimental and bioinformatics methods. Before joining the BIH @Charité as the BIH Johanna Quandt Professor for Early Cancer Development and Prevention, she conducted research at the Broad Institute, Massachusetts General Hospital, and Harvard Medical School in Boston, USA, where she still holds affiliations.
I am building a database of molecular alterations in healthy tissue for comparative analysis with cancer, aiming to decipher the earliest stages of cancer development.
Ambitious, Affable, Active
My research focuses on the discovery of the cell-of-origin of uncommon gynecological and breast cancers, exploiting cutting-edge techniques and establishing novel assays.
Curious, Determined, Positive
The aim of my research is to investigate the molecular mechanisms underlying tamoxifen-associated uterine cancer development, with the goal of developing a screening method.
Open, Thorough, Joyful
I am analyzing scRNA-seq data from normal breast tissue, DCIS and breast cancer to facilitate insights into the molecular landscape and cellular heterogeneity.
Determined, Adventurous, Friendly
I am the go-to person for all administrative needs at the Kübler Lab. Being a non-scientist, it fills me with excitement to contribute to the research in this capacity.
Curious, Open-minded, Friendly
My mission is to set up a well-organized, safe and clean laboratory and to support the group in establishing and validating molecular multi-omics techniques.
Diligent, Well-organized, Empathetic
My project focuses on investigating the epigenomic landscape of mucinous ovarian cancer from cell lines and FFPE tissue samples.
Reliable, Tenacious, Resourceful
As a scientist-turned-scientific editor, I support the group in publishing and communicating their work on cancer development to different audiences.
Curious, Creative, Ambitious
My research aims to identify the cell type susceptible to genomic alterations and to analyze clonal expansion in normal and precancerous tissues of ovarian cancer patients.
Passionate, Persevering, Optimistic
Join our Cancer Research Team. We are constantly seeking passionate individuals who share our dedication to cancer research. If you are eager to make a difference and contribute to groundbreaking advancements in the field, we want to hear from you. To express your interest, reach out to kirsten.kuebler[at]bih-charite.de
The Kübler Lab
Prof. Dr. Kirsten Kübler
Berlin Institute of Health at Charité (BIH)
Campus Benjamin Franklin (CBF)