Research Group Prof. Dr. Henner Farin

Experimental models of the colon cancer microenvironment

Our research group is investigating the cellular and molecular processes in the development of colorectal cancer. In particular, we are interested in the communication of different cell types in the immediate surrounding of the tumor, the so-called “tumor microenvironment”. For this purpose, we use “organoids”, a novel three-dimensional tissue culture system.

Colorectal cancer (CRC) is a leading cause of cancer-related deaths and is characterized by multiple genetic and epigenetic alterations. The individual tumor phenotype is strongly influenced by the tumor microenvironment that includes surrounding fibroblasts, vasculature, and immune cells. To study this complex disease and develop personalized therapeutic strategies a comprehensive approach is required.

Patient-derived tumor organoids and co-culture models

Patient derived organoids (PDOs) have emerged as a research tool that mimics the 3D organization of the gastrointestinal epithelium. Furthermore, co-cultures with stromal cells can be performed to recreate a tissue-like context. PDOs can be expanded and cryopreserved as “living biobanks” that represent the tumor heterogeneity among patients. In collaboration with the University Tumor Center Frankfurt and supported by Frankfurt Cancer Institute (FCI), we are operating the FCI Organoid Biobank to provide support for culture and analysis of PDOs.

Genetic regulators of the CRC microenvironment

Tissue homeostasis depends on the interaction of stem cells with signals from the microenvironment. In tumors, this interaction is perturbed causing uncontrolled growth. To study tissue crosstalk we employ organoid co-cultures and transplantation models. Recently, we have identified that tumor mutations that activate Wnt signaling also influence cancer-associated fibroblasts (CAFs). Wnt inhibition induces a CAF subtype that renders tumor cells more invasive (Mosa et al., Cancer Research 2020), highlighting how stromal cell plasticity can regulate tumor malignancy.

To study influences of the tumor microenvironment on a global level we have performed genetic screens in human colon organoids using the CRISPR/Cas9 technology. This allows unbiased identification of tumor suppressor genes that promote growth in vitro and after organoid xenotransplantation (Michels et al., Cell Stem Cell 2020). In future, this platform could help to discover individualized therapeutic targets for colon cancer.

Personalized models for CRC therapy and pharmacogenomic screening

PDOs can serve as a preclinical model to identify therapeutic strategies. In collaboration with Prof. Wels (Georg-Speyer-Haus), we have used chimeric antigen receptors (CAR)-modified NK cells to induce cytotoxicity of CRC cells. We have developed enzymatic and live imaging assays to evaluate efficacy CAR cells (Schnalzger et al., EMBO Journal 2019).

As participant of the EU-consortium “EUbOPEN” (Enabling and unlocking biology in the OPEN, 2020-2024), we have developed a PDO drug screening platform. The EUbOPEN consortium is funded by the Innovative Medicines Initiative (IMI2) and aims to generate an open access chemogenomic library of compounds covering the “druggable human genome”. Together with our partners from academia and pharmacologic industry, we develop “Human

Tissue Assays” for CRC. We conduct high-throughput pharmacologic screens using the organoid biobank to identify resistance mechanisms and therapeutic strategies.

The EUbOPEN project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 875510. This Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation programme, EFPIA companies and Associated Partners: KTH, OICR, Diamond and McGill. This communication reflects the views of the authors and neither IMI nor the European Union, EFPIA or any Associated Partners are liable for any use that may be made of the information contained herein.

The EUbOPEN project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 875510. This Joint Undertaking receives support from the European Union's Horizon 2020 research and innovation programme, EFPIA companies and Associated Partners: KTH, OICR, Diamond and McGill. This communication reflects the views of the authors and neither IMI nor the European Union, EFPIA or any Associated Partners are liable for any use that may be made of the information contained herein.

Team

Mirja Brüggemann

MSNZ Clinician Scientist

Patrick Wisser

Doctoral Researcher

Yuan Zhou

Doctoral Researcher (Goethe University Frankfurt)

Selected Publications

Schnalzger TE, de Groot MHP, Zhang C, Mosa MH, Michels BE, Röder J, Darvishi T, Wels WS, Farin HF. (2019)
3D model for CAR-mediated cytotoxicity using patient-derived colorectal cancer organoids.
The EMBO Journal. 38(12):e100928.

Michels BE, Mosa MH, Streibl BI, Zhan T, Menche C, Abou-El-Ardat K, Darvishi T, Członka E, Wagner S, Winter J, Medyouf H. Boutros M, Farin HF. (2020)
Pooled In Vitro and In Vivo CRISPR-Cas9 Screening Identifies Tumor Suppressors in Human Colon Organoids.
Cell Stem Cell. 26: 782-792.e7.

Farin HF*, Mosa MH, Ndreshkjana B, Grebbin BM, Ritter B, Menche C, Kennel KB, Ziegler PK, Szabo L, Bollrath J, Rieder D, Michels BE, Kress A, Bozlar M, Darvishi T, Stier S, Kur I-M, Bankov K, Kesselring R, Fichtner-Feigl S, Brune B, Goetze TO, Al-Batran S-E, Brandts CH, Bechstein WO, Wild PJ, Weigert A, Muller S, Knapp S, Trajanoski Z, Greten FR*. (2023)
Colorectal cancer organoid-stroma biobank allows subtype-specific assessment of individualized therapy responses.
Cancer Discovery. 13(10):2192–2211. * corresponding authors

Menche C*, Schuhwerk H*, Armstark I, Gupta P, Fuchs K, van Roey R, Mosa MH, Hartebrodt A, Hajjaj Y, Clavel Ezquerra A, Selvaraju MK, Geppert CI, Bärthel S, Saur D, Greten FR, Brabletz S, Blumenthal DB, Weigert A, Brabletz T**, Farin HF**, Stemmler MP**. (2024)
ZEB1-mediated fibroblast polarization controls inflammation and sensitivity to immunotherapy in colorectal cancer.
EMBO reports. 25(8):3406–3431. * first authors ** corresponding authors

Issing C*, Menche C, Richter MR, Mosa MH, von der Grün J, Fleischmann M, Thoenissen P, Winkelmann R, Darvishi T, Loth AG, Ghanaati S, Rödel F, Wild PJ, Brandts CH, Stöver T, Farin HF*. (2025)
Head and neck tumor organoid biobank for modelling individual responses to radiation therapy according to the TP53/HPV status.
J Exp Clin Cancer Res. 2025 Mar 5;44(1):85. doi: 10.1186/s13046-025-03345-3.
PMID: 40045309 Free PMC article. * corresponding authors

More Publications

Jan Dreute
Julia Stengel
Jonas Becher
David van den Borre
Maximilian Pfisterer
Marek Bartkuhn
Vanessa M Beutgen
Benardina Ndreshkjana
Ulrich Gärtner
Johannes Graumann
Michael Huck
Stephan Klatt
Chloe Leff
Henner F Farin
Andrea Nist
Roland Schmitz
Thorsten Stiewe
Julia Teply-Szymanski
Jochen Wilhelm
Alfredo Cabrera-Orefice
M Lienhard Schmitz

Synergistic targeting of cancer cells through simultaneous inhibition of key metabolic enzymes

Cell Death Differ. 2025 Dec;32(12):2239-2256. doi: 10.1038/s41418-025-01532-5. Epub 2025 Jun 23.

ABSTRACT

As cancer cell specific rewiring of metabolic networks creates…

Research Group Prof. Dr. Henner Farin

Experimental models of the colon cancer microenvironment

Patient-derived tumor organoids and co-culture models

Personalized models for CRC therapy and pharmacogenomic screening

Dr. Szilvia Baron

Mirja Brüggemann

Maria Correia da Silva Melo

Tahmineh Darvishi

Prof. Dr. Henner Farin

Dr. med. Christian Issing

Alena Kress

Dr. Constantin Menche

Dr. Benardina Ndreshkjana

Haifa Parkar

Sara Stier

Patrick Wisser

Yuan Zhou

Synergistic targeting of cancer cells through simultaneous inhibition of key metabolic enzymes

Head and neck tumor organoid biobank for modelling individual responses to radiation therapy according to the TP53/HPV status

Author Correction: Octyl itaconate enhances VSVΔ51 oncolytic virotherapy by multitarget inhibition of antiviral and inflammatory pathways

Toward target 2035: EUbOPEN - a public-private partnership to enable & unlock biology in the open

Establishment of Patient-Derived Organoids from Colorectal Cancer Resection Samples

ZEB1-mediated fibroblast polarization controls inflammation and sensitivity to immunotherapy in colorectal cancer

Octyl itaconate enhances VSVΔ51 oncolytic virotherapy by multitarget inhibition of antiviral and inflammatory pathways

Downregulation of V-ATPase V0 Sector Induces Microvillus Atrophy Independently of Apical Trafficking in the Mammalian Intestine

Functional and spatial proteomics profiling reveals intra- and intercellular signaling crosstalk in colorectal cancer

Colorectal Cancer Organoid-Stroma Biobank Allows Subtype-Specific Assessment of Individualized Therapy Responses

Actin dynamics regulation by TTC7A/PI4KIIIα limits DNA damage and cell death under confinement

Deep Annotation of Donated Chemical Probes (DCP) in Organotypic Human Liver Cultures and Patient-Derived Organoids from Tumor and Normal Colorectum

Synthetic enforcement of STING signaling in cancer cells appropriates the immune microenvironment for checkpoint inhibitor therapy

Immune escape of colorectal tumours via local LRH-1/Cyp11b1-mediated synthesis of immunosuppressive glucocorticoids

Loss of SUV420H2-Dependent Chromatin Compaction Drives Right-Sided Colon Cancer Progression

Expansion of T memory stem cells with superior anti-tumor immunity by Urolithin A-induced mitophagy

Strategies for genetic manipulation of adult stem cell-derived organoids

A Wnt-Induced Phenotypic Switch in Cancer-Associated Fibroblasts Inhibits EMT in Colorectal Cancer

AKT-dependent NOTCH3 activation drives tumor progression in a model of mesenchymal colorectal cancer

Cellular and Molecular Changes of Brain Metastases-Associated Myeloid Cells during Disease Progression and Therapeutic Response

Pooled In Vitro and In Vivo CRISPR-Cas9 Screening Identifies Tumor Suppressors in Human Colon Organoids

Conformation-specific inhibitors of activated Ras GTPases reveal limited Ras dependency of patient-derived cancer organoids

STAT3 activation through IL-6/IL-11 in cancer-associated fibroblasts promotes colorectal tumour development and correlates with poor prognosis

3D model for CAR-mediated cytotoxicity using patient-derived colorectal cancer organoids

Cancer-induced inflammation and inflammation-induced cancer in colon: a role for S1P lyase

Human colon organoids reveal distinct physiologic and oncogenic Wnt responses

The transcriptional regulator FUBP1 influences disease outcome in murine and human myeloid leukemia

Dynamic Formation of Microvillus Inclusions During Enterocyte Differentiation in Munc18-2-Deficient Intestinal Organoids

Intestinal Inflammation and Dysregulated Immunity in Patients With Inherited Caspase-8 Deficiency

YAP-IL-6ST autoregulatory loop activated on APC loss controls colonic tumorigenesis

Tbx2 and Tbx3 Act Downstream of Shh to Maintain Canonical Wnt Signaling during Branching Morphogenesis of the Murine Lung

Generation of an inducible colon-specific Cre enzyme mouse line for colon cancer research

Lack of Genetic Interaction between Tbx18 and Tbx2/Tbx20 in Mouse Epicardial Development

Misexpression of Tbx18 in cardiac chambers of fetal mice interferes with chamber-specific developmental programs but does not induce a pacemaker-like gene signature

Visualization of a short-range Wnt gradient in the intestinal stem-cell niche

Replacement of Lost Lgr5-Positive Stem Cells through Plasticity of Their Enterocyte-Lineage Daughters

Germline deletions in the tumour suppressor gene FOCAD are associated with polyposis and colorectal cancer development

Plasticity within stem cell hierarchies in mammalian epithelia

Immune deficiency-related enteropathy-lymphocytopenia-alopecia syndrome results from tetratricopeptide repeat domain 7A deficiency

TTC7A, a critical effector for the intestinal and immune system homeostasis

Paneth cell extrusion and release of antimicrobial products is directly controlled by immune cell-derived IFN-γ

Human intestinal tissue with adult stem cell properties derived from pluripotent stem cells

Niche-independent high-purity cultures of Lgr5+ intestinal stem cells and their progeny

TTC7A mutations disrupt intestinal epithelial apicobasal polarity

Generation of L cells in mouse and human small intestine organoids

Retromer dependent recycling of the Wnt secretion factor Wls is dispensable for stem cell maintenance in the mammalian intestinal epithelium

Tbx2 terminates shh/fgf signaling in the developing mouse limb bud by direct repression of gremlin1

Tbx2 controls lung growth by direct repression of the cell cycle inhibitor genes Cdkn1a and Cdkn1b

Tbx18 function in epicardial development

Redundant sources of Wnt regulate intestinal stem cells and promote formation of Paneth cells

Canonical Wnt signaling regulates smooth muscle precursor development in the mouse ureter

Controlled gene expression in primary Lgr5 organoid cultures

Tbx2 and Tbx3 induce atrioventricular myocardial development and endocardial cushion formation

Hydroureternephrosis due to loss of Sox9-regulated smooth muscle cell differentiation of the ureteric mesenchyme

Tbx20 interacts with smads to confine tbx2 expression to the atrioventricular canal

TBX15 mutations cause craniofacial dysmorphism, hypoplasia of scapula and pelvis, and short stature in Cousin syndrome

T-box protein Tbx18 interacts with the paired box protein Pax3 in the development of the paraxial mesoderm

Transcriptional repression by the T-box proteins Tbx18 and Tbx15 depends on Groucho corepressors

New Research Alliance to Explore the Sinister Network of Colorectal Tumors

Heisenberg Professorship for Experimental Model Systems in Tumor Biology: Henner Farin

ZEB1-Factor increases chances of success of immunotherapy

Henner Farin receives funding through the DFG Heisenberg Program

Downregulation of V-ATPase V₀ Sector Induces Microvillus Atrophy Independently of Apical Trafficking in the Mammalian Intestine