Cancer Progression and Metastasis

Our Research

Metastasis is a multistep process, with a complex evolution, where cells leave the primary tumor and seed to distant organs. Every step during metastasis adds considerable heterogeneity to the tumor and includes the acquisition of stem cell features. These cancer stem cell populations have distinct molecular, genetic and phenotypic features, which jointly increase the risk of therapy resistance. However, the tumor microenvironment can control phenotypic plasticity of cancer stem cells.

We utilize unbiased multi-omics (transcriptome, epigenome, methylome) at single cell level, functional genomics and lineage tracing approaches to analyze stem cell plasticity with complex in vivo models of metastatic colorectal cancer. These genetically engineered mouse models contain alterations and show progression similarly to human metastatic colorectal cancer. Further, these models allow tumor progression in the native tumor microenvironment, which enables us to investigate the role of non-cell-autonomous factors that control cancer stem cells features during metastasis. Our lab has a strong expertise in the use of genetically engineered mouse models, to analyze each step of molecular and cellular changes during the metastatic process longitudinally and in response to therapy. We also use primary clinical samples and patient derived organoids to better understand the most lethal stages of the disease.

To understand the mechanisms of colorectal cancer progression this division will focus on the following major topics:

Functional characterization of cancer stem cells in tumor-evolution
Molecular and cellular basis of cancer stem cell niches
Analysis of cancer stem cells and the interaction with the tumor microenvironment as driver of therapy resistance

Our research will broaden our understanding of the mechanisms that control colorectal cancer progression and will help to find therapeutic vulnerabilities of late stage cancers.

Projects

TROPHIT1 is an open label, randomized, multicenter phase II/III trial to investigate the efficacy of Sacituzumab Govitecan a TROP2 targeting anti-body drug conjugate in metastatic colorectal cancer.

TROPHIT1 was initiated based on our research findings in collaboration with the National Center for Tumor Diseases (NCT) Heidelberg. We conduct a translational research program, including single cell sequencing, liquid biopsy analysis and spatial transcriptomics to unravel determinants of cellular plasticity and therapy response.

https://www.esmogastro.org/article/S2949-8198(24)00079-7/pdf

Team

Dr. Rene-Filip Jackstadt

Junior Group Leader
Carolin Artmann

Technical Assistant
Ioannis Chiotakakos

PhD Student
Gabriele Diamante

PhD Student
Raja Flüchter

Research Assistant
Nikolaos Georgakopoulos

PhD Student
Aitana Guiseris Martinez

PhD Student
Manuel Mastel

PhD Student
Jasmin Meier

Lab Manager
Luisa Nader

Clinician Scientist
Gabriele Schmidt

Research Assistant
Thorben Söhngen

PhD Student

Entire Team

Selected publications

2025 - ESMO Gastrointestinal Oncology

TROPHIT1 - a randomized, open-label, multicenter, phase II/III trial of sacituzumab govitecan compared to standard of care in metastatic colorectal cancer patients

B.C. Köhler, G.M. Haag, L. Le Cornet, P. Hoffmeister-Wittmann, M. Schmidt, A. Manjunath, N. Vaquero-Siguero, M. Jenzer, M. Gimmel, A. Stahler, A. Stein, M. Reichert, S. Kasper, M. Bitzer, D. Jäger, C. Springfeld, T.F. Weber, S. Fröhling, K. Steindorf, A. Trumpp, R.F. Schlenk, R. Jackstadt

2022 - International Journal of Cancer

From organoids to bedside: Advances in modeling, decoding and targeting of colorectal cancer

Betge J, Jackstadt R

2022 - Science Immunology

Rgs16 promotes antitumor CD8+ T cell exhaustion

Weisshaar N, Wu J, Ming Y, Madi A, Hotz-Wagenblatt A, Ma S, Mieg A, Hering M, Zettl F, Mohr K, Schlimbach T, Ten Bosch N, Hertel F, Müller L, Byren H, Wang M, Borgers H, Munz M, Schmitt L, van der Hoeven F, Kloz U, Carretero R, Schleußner N, Jackstadt RF, Hofmann I, Cui G

2021 - Cancer Cell

Single-cell analysis defines a pancreatic fibroblast lineage that supports anti-tumor immunity

Hutton C, Heider F, Blanco-Gomez A, Banyard A, Kononov A, Zhang X, Karim S, Paulus-Hock V, Watt D, Steele N, Kemp S, Hogg EKJ, Kelly J, Jackstadt RF, Lopes F, Menotti M, Chisholm L, Lamarca A, Valle J, Sansom OJ, Springer C, Malliri A, Marais R, Pasca di Magliano M, Zelenay S, Morton JP, Jørgensen C

2019 - Cancer Cell

Epithelial NOTCH signaling rewires the tumor microenvironment of colorectal cancer to drive poor-prognosis subtypes and metastasis

Jackstadt R, van Hooff SR, Leach JD, Cortes-Lavaud X, Lohuis JO, Ridgway RA, Wouters VM, Roper J, Kendall TJ, Roxburgh CS, Horgan PG, Nixon C, Nourse C, Gunzer M, Clark W, Hedley A, Yilmaz OH, Rashid M, Bailey P, Biankin AV, Campbell AD, Adams DJ, Barry ST, Steele CW, Medema JP, Sansom OJ

Open Positions

Our research group is always looking for enthusiastic team members.

Postdoctoral researchers: Please contact Rene Jackstadt by email and include a cover letter outlining your research interests, your CV with a complete publication list, and the contact details of three references.

Clinician/Physician scientists: Please apply through the DKFZ Clinician Scientist Program and also send your application directly to Rene Jackstadt.

Doctoral students: Please use the International PhD Program at DKFZ to apply and simultaneously send your application to Dr. Rene Jackstadt.

Master's students: Please send your application by email to Rene Jackstadt and include a cover letter outlining your research interests and your CV.

Posterprize for Manuel Mastel

Manuel won the prize for best scientific poster at the 2nd animal models of cancer conference 2025 in Punta Cana, Dominican Republic.

Congratulations!!!

PhD Scholarship

The Merck Society for Arts and Science has awarded Aitana Guiseris Martinez the doctoral scholarship in translational medicine this year. We congratulate her on this recognition.

2nd Heidelberg Polyposis Congres

On Saturday, February 22, 2025, the 2nd Heidelberg Polyposis Congress took place at the University Hospital Heidelberg.

Under the title "This is why we need research," the interdisciplinary project PROTECT (Progression and Transformation of Early Colorectal Cancer and Therapy) was presented.

Congratulations on your PhD

We warmly congratulate Nuria Vaquero Siguero on successfully completing her PhD and celebrate with her the outstanding achievement of "Summa Cum Laude."