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

Dr. Szilvia Baron

Dr. Szilvia Baron

Staff Scienstist, FCI Organoid Biobank

Maria Correia da Silva Melo

Maria Correia da Silva Melo

Doctoral Researcher

Tahmineh Darvishi

Tahmineh Darvishi

Lab Manager

Prof. Dr. Henner Farin

Prof. Dr. Henner Farin

Group Leader

Dr. med. Christian Issing

Dr. med. Christian Issing

MSNZ Clinician Scientist

Alena Kress

Alena Kress

Doctoral Researcher

Dr. Constantin Menche

Dr. Constantin Menche

Researcher, DKTK Organoid Platform

Dr. Benardina Ndreshkjana

Dr. Benardina Ndreshkjana

Postdoc

Vanessa Schmidt

Vanessa Schmidt

Technician, DKTK Organoid Platform

Placeholder Image

Sara Stier

Technician

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

  • Naziia Kurmasheva
  • Aida Said
  • Boaz Wong
  • Priscilla Kinderman
  • Xiaoying Han
  • Anna H F Rahimic
  • Alena Kress
  • Madalina E Carter-Timofte
  • Emilia Holm
  • Demi van der Horst
  • Christoph F Kollmann
  • Zhenlong Liu
  • Chen Wang
  • Huy-Dung Hoang
  • Elina Kovalenko
  • Maria Chrysopoulou
  • Krishna Sundar Twayana
  • Rasmus N Ottosen
  • Esben B Svenningsen
  • Fabio Begnini
  • Anders E Kiib
  • Florian E H Kromm
  • Hauke J Weiss
  • Daniele Di Carlo
  • Michela Muscolini
  • Maureen Higgins
  • Mirte van der Heijden
  • Rozanne Arulanandam
  • Angelina Bardoul
  • Tong Tong
  • Attila Ozsvar
  • Wen-Hsien Hou
  • Vivien R Schack
  • Christian K Holm
  • Yunan Zheng
  • Melanie Ruzek
  • Joanna Kalucka
  • Laureano de la Vega
  • Walid A M Elgaher
  • Anders R Korshoej
  • Rongtuan Lin
  • John Hiscott
  • Thomas B Poulsen
  • Luke A O'Neill
  • Dominic G Roy
  • Markus M Rinschen
  • Nadine van Montfoort
  • Jean-Simon Diallo
  • Henner F Farin
  • Tommy Alain
  • David Olagnier

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

Nat Commun. 2024 Dec 19;15(1):10698. doi: 10.1038/s41467-024-55044-w.

NO ABSTRACT

PMID:39702301 | PMC:PMC11659427 | DOI:10.1038/s41467-024-55044-w

  • Claudia Tredup
  • Suzanne Ackloo
  • Hartmut Beck
  • Peter J Brown
  • Alex N Bullock
  • Alessio Ciulli
  • Ivan Dikic
  • Kristina Edfeldt
  • Aled M Edwards
  • Jonathan M Elkins
  • Henner F Farin
  • Edward A Fon
  • Matthias Gstaiger
  • Judith Günther
  • Anna-Lena Gustavsson
  • Sandra Häberle
  • Laura Isigkeit
  • Kilian V M Huber
  • Andras Kotschy
  • Oliver Krämer
  • Andrew R Leach
  • Brian D Marsden
  • Hisanori Matsui
  • Daniel Merk
  • Florian Montel
  • Monique P C Mulder
  • Susanne Müller
  • Dafydd R Owen
  • Ewgenij Proschak
  • Sandra Röhm
  • Alexandra Stolz
  • Michael Sundström
  • Frank von Delft
  • Timothy M Willson
  • Cheryl H Arrowsmith
  • Stefan Knapp

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

RSC Med Chem. 2024 Nov 29. doi: 10.1039/d4md00735b. Online ahead of print.

ABSTRACT

Target 2035 is a global initiative that seeks to identify a pharmacological modulator…

  • Didem Seven
  • Szilvia Baron
  • Henner F Farin

Establishment of Patient-Derived Organoids from Colorectal Cancer Resection Samples

Methods Mol Biol. 2024 Nov 10. doi: 10.1007/7651_2024_575. Online ahead of print.

ABSTRACT

Colorectal cancer (CRC) organoids can serve as powerful preclinical cell…

  • Constantin Menche
  • Harald Schuhwerk
  • Isabell Armstark
  • Pooja Gupta
  • Kathrin Fuchs
  • Ruthger van Roey
  • Mohammed H Mosa
  • Anne Hartebrodt
  • Yussuf Hajjaj
  • Ana Clavel Ezquerra
  • Manoj K Selvaraju
  • Carol I Geppert
  • Stefanie Bärthel
  • Dieter Saur
  • Florian R Greten
  • Simone Brabletz
  • David B Blumenthal
  • Andreas Weigert
  • Thomas Brabletz
  • Henner F Farin
  • Marc P Stemmler

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

EMBO Rep. 2024 Aug;25(8):3406-3431. doi: 10.1038/s44319-024-00186-7. Epub 2024 Jun 27.

ABSTRACT

The EMT-transcription factor ZEB1 is heterogeneously expressed in tumor…

  • Naziia Kurmasheva
  • Aida Said
  • Boaz Wong
  • Priscilla Kinderman
  • Xiaoying Han
  • Anna H F Rahimic
  • Alena Kress
  • Madalina E Carter-Timofte
  • Emilia Holm
  • Demi van der Horst
  • Christoph F Kollmann
  • Zhenlong Liu
  • Chen Wang
  • Huy-Dung Hoang
  • Elina Kovalenko
  • Maria Chrysopoulou
  • Krishna Sundar Twayana
  • Rasmus N Ottosen
  • Esben B Svenningsen
  • Fabio Begnini
  • Anders E Kiib
  • Florian E H Kromm
  • Hauke J Weiss
  • Daniele Di Carlo
  • Michela Muscolini
  • Maureen Higgins
  • Mirte van der Heijden
  • Rozanne Arulanandam
  • Angelina Bardoul
  • Tong Tong
  • Attila Ozsvar
  • Wen-Hsien Hou
  • Vivien R Schack
  • Christian K Holm
  • Yunan Zheng
  • Melanie Ruzek
  • Joanna Kalucka
  • Laureano de la Vega
  • Walid A M Elgaher
  • Anders R Korshoej
  • Rongtuan Lin
  • John Hiscott
  • Thomas B Poulsen
  • Luke A O'Neill
  • Dominic G Roy
  • Markus M Rinschen
  • Nadine van Montfoort
  • Jean-Simon Diallo
  • Henner F Farin
  • Tommy Alain
  • David Olagnier

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

Nat Commun. 2024 May 15;15(1):4096. doi: 10.1038/s41467-024-48422-x.

ABSTRACT

The presence of heterogeneity in responses to oncolytic virotherapy poses a barrier to…

  • Aurélien Bidaud-Meynard
  • Anne Bourdais
  • Ophélie Nicolle
  • Maela Duclos
  • Jad Saleh
  • Frank M Ruemmele
  • Henner F Farin
  • Delphine Delacour
  • Despina Moshous
  • Grégoire Michaux

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

Cell Mol Gastroenterol Hepatol. 2024;17(6):1072-1075. doi: 10.1016/j.jcmgh.2024.02.011. Epub 2024 Feb 16.

NO ABSTRACT

PMID:38369130 | PMC:PMC11127621 | DOI:10.1016/j.jcmgh.2024.02.011

  • Christina Plattner
  • Giorgia Lamberti
  • Peter Blattmann
  • Alexander Kirchmair
  • Dietmar Rieder
  • Zuzana Loncova
  • Gregor Sturm
  • Stefan Scheidl
  • Marieke Ijsselsteijn
  • Georgios Fotakis
  • Asma Noureen
  • Rebecca Lisandrelli
  • Nina Böck
  • Niloofar Nemati
  • Anne Krogsdam
  • Sophia Daum
  • Francesca Finotello
  • Antonios Somarakis
  • Alexander Schäfer
  • Doris Wilflingseder
  • Miguel Gonzalez Acera
  • Dietmar Öfner
  • Lukas A Huber
  • Hans Clevers
  • Christoph Becker
  • Henner F Farin
  • Florian R Greten
  • Ruedi Aebersold
  • Noel F C C de Miranda
  • Zlatko Trajanoski

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

iScience. 2023 Nov 4;26(12):108399. doi: 10.1016/j.isci.2023.108399. eCollection 2023 Dec 15.

ABSTRACT

Precision oncology approaches for patients with colorectal cancer…

  • Henner F Farin
  • Mohammed H Mosa
  • Benardina Ndreshkjana
  • Britta M Grebbin
  • Birgit Ritter
  • Constantin Menche
  • Kilian B Kennel
  • Paul K Ziegler
  • Lili Szabó
  • Julia Bollrath
  • Dietmar Rieder
  • Birgitta E Michels
  • Alena Kress
  • Müge Bozlar
  • Tahmineh Darvishi
  • Sara Stier
  • Ivan-Maximilano Kur
  • Katrin Bankov
  • Rebecca Kesselring
  • Stefan Fichtner-Feigl
  • Bernhard Brüne
  • Thorsten O Goetze
  • Salah-Eddin Al-Batran
  • Christian H Brandts
  • Wolf O Bechstein
  • Peter J Wild
  • Andreas Weigert
  • Susanne Müller
  • Stefan Knapp
  • Zlatko Trajanoski
  • Florian R Greten

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

Cancer Discov. 2023 Oct 5;13(10):2192-2211. doi: 10.1158/2159-8290.CD-23-0050.

ABSTRACT

In colorectal cancers, the tumor microenvironment plays a key role in prognosis…

  • Tania Gajardo
  • Mathilde Bernard
  • Marie Lô
  • Elisa Turck
  • Claire Leveau
  • Marie-Thérèse El-Daher
  • Alexandre Deslys
  • Patricia Panikulam
  • Constantin Menche
  • Mathieu Kurowska
  • Gregoire Le Lay
  • Lucie Barbier
  • Despina Moshous
  • Bénédicte Neven
  • Henner F Farin
  • Alain Fischer
  • Gaël Ménasché
  • Geneviève de Saint Basile
  • Pablo Vargas
  • Fernando E Sepulveda

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

J Allergy Clin Immunol. 2023 Oct;152(4):949-960. doi: 10.1016/j.jaci.2023.06.016. Epub 2023 Jun 29.

ABSTRACT

BACKGROUND: The actin cytoskeleton has a crucial role in the…

  • Claudia Tredup
  • Benardina Ndreshkjana
  • Natalie S Schneider
  • Amelie Tjaden
  • Aurino M Kemas
  • Sonia Youhanna
  • Volker M Lauschke
  • Benedict-Tilman Berger
  • Andreas Krämer
  • Lena M Berger
  • Sandra Röhm
  • Stefan Knapp
  • Henner F Farin
  • Susanne Müller

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

ACS Chem Biol. 2023 Apr 21;18(4):822-836. doi: 10.1021/acschembio.2c00877. Epub 2023 Mar 21.

ABSTRACT

Well-characterized small molecules are essential tools for studying…

  • Larsen Vornholz
  • Sophie E Isay
  • Zsuzsanna Kurgyis
  • Daniel C Strobl
  • Patricia Loll
  • Mohammed H Mosa
  • Malte D Luecken
  • Michael Sterr
  • Heiko Lickert
  • Christof Winter
  • Florian R Greten
  • Henner F Farin
  • Fabian J Theis
  • Jürgen Ruland

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

Sci Adv. 2023 Mar 17;9(11):eadd8564. doi: 10.1126/sciadv.add8564. Epub 2023 Mar 15.

ABSTRACT

Immune checkpoint inhibitors (ICIs) enhance anticancer immunity by releasing…

  • Asma Ahmed
  • Cindy Reinhold
  • Eileen Breunig
  • Truong San Phan
  • Lea Dietrich
  • Feodora Kostadinova
  • Corinne Urwyler
  • Verena M Merk
  • Mario Noti
  • Israel Toja da Silva
  • Konstantin Bode
  • Fatima Nahle
  • Anna Pia Plazzo
  • Julia Koerner
  • Regula Stuber
  • Constantin Menche
  • Eva Karamitopoulou
  • Henner F Farin
  • Kenneth J Gollob
  • Thomas Brunner

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

Mol Oncol. 2023 Aug;17(8):1545-1566. doi: 10.1002/1878-0261.13414. Epub 2023 Mar 9.

ABSTRACT

Control of tumour development and growth by the immune system critically…

  • Verawan Boonsanay
  • Mohammed H Mosa
  • Mario Looso
  • Dieter Weichenhan
  • Fatih Ceteci
  • Lorenz Pudelko
  • Andre Lechel
  • Christian S Michel
  • Carsten Künne
  • Henner F Farin
  • Christoph Plass
  • Florian R Greten

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

Gastroenterology. 2023 Feb;164(2):214-227. doi: 10.1053/j.gastro.2022.10.036. Epub 2022 Nov 17.

ABSTRACT

BACKGROUND & AIMS: Epigenetic processes regulating gene…

  • Dominic Denk
  • Valentina Petrocelli
  • Claire Conche
  • Moritz Drachsler
  • Paul K Ziegler
  • Angela Braun
  • Alena Kress
  • Adele M Nicolas
  • Kathleen Mohs
  • Christoph Becker
  • Markus F Neurath
  • Henner F Farin
  • Christian J Buchholz
  • Pénélope A Andreux
  • Chris Rinsch
  • Florian R Greten

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

Immunity. 2022 Nov 8;55(11):2059-2073.e8. doi: 10.1016/j.immuni.2022.09.014. Epub 2022 Oct 19.

ABSTRACT

T memory stem cells (TSCM) display increased self-renewal and…

  • Constantin Menche
  • Henner F Farin

Strategies for genetic manipulation of adult stem cell-derived organoids

Exp Mol Med. 2021 Oct;53(10):1483-1494. doi: 10.1038/s12276-021-00609-8. Epub 2021 Oct 18.

ABSTRACT

Organoid technology allows the expansion of primary epithelial cells…

News

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

PD Dr. rer. nat. Henner Farin took up his appointment as Heisenberg Professor (W2) for “Experimental Model Systems in Tumor Biology” at the Institute of Tumor Biology and Experimental Therapy at the Georg-Speyer-Haus on January 1, 2025.

04.01.2025 Farin
[Translate to English:] Ernennung durch den Dekan der Medizinischen Fakultät der Goethe-Universität Frankfurt am Main (Prof. Dr. med. Stefan Zeuzem)

ZEB1-Factor increases chances of success of immunotherapy

Factor in connective tissue cells (ZEB1) modulates the efficacy of immunotherapy in colorectal carcinomas

04.07.2024 Farin
PD Dr. Henner Farin

Henner Farin receives funding through the DFG Heisenberg Program

The Georg-Speyer-Haus scientist is accepted into the Heisenberg Program of the German Research Foundation (DFG)

 

12.11.2023 Farin
PD Dr. Henner Farin

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