Early Cancer Development and Prevention

About

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.

KueblerLab_DNA_sequencer

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.

Major Publications

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.

News

Collaborations

Team

Professorin Kirsten Kübler

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.

Affiliations

Leonie Stockschläder
Postdoctoral Fellow (comp)

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

Francesca Tiso
Postdoctoral Fellow (exp)

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

Yumisa Ellinger
MD Thesis Student (exp)

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

Ali Maeve FitzGerald
Student Research Assistant (comp)

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

Carola Herrmann
Administrative Assistant

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

Martina Wasser
Lab Technician/Lab Manager

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

Sanket Gosavi
Master Thesis Student (exp/comp)

My project focuses on investigating the epigenomic landscape of mucinous ovarian cancer from cell lines and FFPE tissue samples.

Reliable, Tenacious, Resourceful

Regine Armann
Scientific Writer/Project Manager

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

Claudia Marti Grifol
PhD Student (exp)

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

Jule Brenningmeyer
Master Thesis Student (comp)

I develop a Snakemake pipeline to analyze somatic variants in
pancreatic adenocarcinoma, identify driver mutations, and characterize
the cancer cell-of-origin.

Foto Website_Julia Wejda_02
Julia Weijda
Lab Technician

My aim is to optimize and establish new experimental techniques to
identify the molecular changes that initiate cancer development.

Job Offers

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

Contact

The Kübler Lab
Prof. Dr. Kirsten Kübler

Berlin Institute of Health at Charité (BIH)
Spreepalais
Anna-Louisa-Karsch-Straße 2
10178 Berlin

Campus Benjamin Franklin (CBF)
Hindenburgdamm 30
12203 Berlin