Cell Biology of the Intestine

The Clark lab is currently looking for a PhD researcher for a DFG-funded project investigating cross-talk between mechanosensing and inflammation in the intestine. More details available here.

• Research Summary
• Background
• Ongoing Research
• Lab Members
• Additional Lab Info
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• Open Positions
• Selected Publications

The organization and dynamics of complex tissues relies on the cellular integration of various external signals, for example chemical signals like soluble chemokines during inflammation or mechanical signals from surrounding extracellular matrix networks and neighboring cells. Our lab focuses on understanding the mechanisms that regulate and integrate mechano-chemical signaling pathways and also how the properties and behavior of individual cells in tissues give rise to tissue-scale form and function. We primarily study the intestine, focusing on collective cell behaviors during homeostasis and how dysregulation of these processes contributes to intestinal pathologies such as inflammatory bowel diseases (IBDs) and colorectal cancer. To address these questions, our lab employs a multidisciplinary approach, combining cell biology and live microscopy with quantitative analytical methods, mechanobiology and theoretical modeling.

The mammalian intestine is lined by a sheet of apico-basally polarized epithelial cells that are responsible for nutrient absorption and for providing a barrier against entry of pathogens or unwanted substances into the body. The intestinal epithelium is a well-organized and highly dynamic tissue, with the vast majority of cells exhibiting rapid collective migration and turnover every 3-5 days. The small intestine is segregated into stereotyped patterns of crypts and villi. Crypts contain stem and progenitor cells that, upon differentiation, migrate toward the villus tip and are extruded, all while maintaining a tight epithelial barrier. Defects in barrier function is associated with inflammatory bowel diseases (IBDs), whose prevalence has risen sharply over the past several decades and which present a major risk factor for later development of intestinal cancer. IBDs are characterized by poor epithelial barrier function and chronic inflammation and are influenced by a number of factors including genetic predisposition, diet and the gut microbiota.

A common and potentially dangerous complication of chronical inflammatory diseases like IBDs is fibrosis. Fibrosis is caused by a mechanical stiffening of the tissue due to increased production and remodeling of extracellular matrix networks. Cells possess a number of mechanisms and pathways by which they can sense and respond to changes in the physical properties of their microenvironment. A number of these mechanosensing and mechanotransduction pathways interact with inflammatory pathways, which can lead to positive feedback loops between mechano-inflammatory signaling (Saha et al, 2023).

A major goal of our research is to understand the interactions between mechanosensing and inflammation, especially in the context of IBDs. To accomplish this, we primarily use intestinal organoids grown in 3D or 2D environments. Organoids recapitulate many aspects of the in vivo intestine, including cell type compartmentalization, tissue folding and geometry and collective migration. Organoids are a model uniquely suited to study various aspects of epithelial and intestinal homeostasis such as stem cell renewal, differentiation and wound healing as well as interactions with the immune system and microbiome. In the lab, we employ state-of-the-art organoid culture and microfabrication techniques combined with high-resolution quantitative microscopy and mechanobiology assays to better understand these processes and how individual cell function contributes to overall tissue health and disease.

In addition to studying the cross-talk between intestinal mechanosensing and inflammatory signaling, another major interest in the lab is to understand the mechanisms underlying changes in tissue organization in early stages of intestinal tumorigenesis. We focus on understanding how dysregulation of signaling pathways that contribute to tumor formation, for example Wnt/β-catenin signaling influences parameters such as collective cell migration,  cell-cell and cell-substrate adhesion and tissue fluidity. We also investigate how changes in these parameters can reciprocally regulate signaling pathways. Other projects in the lab use tissue engineering approaches to develop new organ-on-chip and microtissue technologies to better investigate fundamental outstanding questions in intestinal pathophysiology.

Current Lab Members:

Michelle Heinze, Bachelor Thesis Student
Alexander Hene, Bachelor Thesis Student
Lena Seidelmann, Bachelor Thesis Student

Previous Lab Members:
Soufian Kaplan, Master Thesis Student (Current Position : Project and Network Manager, EurA AG)
Marie Touzet-Robin, Master Internship Student (Current Position: Master Student Intern, Institut Curie, Paris)
Lea-Corinna Burbaum, Master Thesis Student (with PD Dr. Dafne Müller; Current Position: PhD Researcher, University Hospital Tübingen)
Sydney Buhrow, Bachelor Summer Internship Student
Benedikt Hermann, Master Thesis Student
Kim-Marie Nguyen, Master Thesis Student (with PD Dr. Dafne Müller)
Karen Kresbach, Master Student (with Prof. Michael Heymann; Current Position: PhD Researcher, University Hospital Münster)
Rico Schill, Bachelor Thesis Student (Current Position: Master Student, TU Munich)
Fabian Gärtner, Bachelor Thesis Student (Current Position: PhD Researcher, Institut Curie, Paris)

Our lab is also affiliated with the Stuttgart Research Center Systems Biology (SRCSB) and the Center for Personalized Medicine at the University of Tübingen (ZPM), with core funding through the Excellence Strategy of the University of Tübingen. For more details on past and present research from the lab as well as additional resources, feel free to check out Andrew’s website.

The Clark lab is currently looking for a PhD researcher for a DFG-funded project investigating cross-talk between mechanosensing and inflammation in the intestine. More details available here.

We are always happy to discuss potential PhD or Postdoctoral positions and funding opportunities. We are also happy to host Bachelor and Master students in the lab. Please contact Andrew with your CV and research interests if you are interested in checking out the lab.

Höpfl S, Özverin M, Nowack H, Tamas R, Clark AG, Radde N and Olayioye MA (2025) Integrated mathematical and experimental modeling uncovers enhanced EMT plasticity upon loss of the DLC1 tu- mor suppressor. PLoS Computational Biology. 21(5): e1013076. https://doi.org/10.1371/journal.pcbi.1013076

Aggrey-Fynn JE, Manjunath M, Rajput A, Abdelrahman AM, Thiel J, Truty MJ, Clark AG, Dong M, Johnsen SA (2025) Therapeutic targeting of FOSL1 and RELA-dependent transcriptional mechanisms to suppress pancreatic cancer metastasis. Cell Death & Disease. 16(1):504. https://doi.org/10.1038/s41419-025-07810-x

Saha S, Müller D and Clark AG (2023) Mechanosensory feedback loops during chronic inflammation. Frontiers in Cell and Developmental Biology. 11:1225677. https://doi.org/10.3389/fcell.2023.1225677

Staneva R and Clark AG (2023) Analysis of collective migration patterns within tumors. In: Mar- gadant, C. (eds) Methods in Molecular Biology - Cell Migration in Three Dimensions. vol 2608. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-2887-4_18

van Stalborch A-MD, Clark AG, Sonnenberg A and Margadant C (2023) Imaging and quantitative analysis of integrin-dependent cell-matrix adhesions. STAR Protocols. 4(3): 102473. https://doi.org/10.1016/j.xpro.2023.102473

Aparicio-Yuste R, Muenkel M, Clark AG, Gomez-Benito MJ and Bastounis EE (2022) A stiff extracel- lular matrix favors the mechanical cell competition that leads to extrusion of bacterially-infected epithelial cells. Frontiers in Cell and Developmental Biology 10: 912318. https://doi.org/10.3389/fcell.2022.912318

Clark AG, Maitra A, Jacques C, Bergert M, Pérez-González C, Simon A, Lederer L, Diz-Muñoz A, Trepat X, Voituriez R and Vignjevic DM (2022) Self-generated gradients steer collective migration on viscoelastic collagen networks. Nature Materials. 21(10): 1200-1210. https://doi.org/10.1101/2020.07.11.198739

Clark, A.G. (2021) Biophysical origins of viscoelasticity during collective cell migration. In: Pajic-Lijakovic, I. and Barriga, E.H. Viscoelasticity and Collective Cell Migration: An interdisciplinary perspective across levels of organization Elsevier/Academic Press, Cambridge, MA, USA. https://doi.org/10.1016/B978-0-12-820310-1.00007-0

Staneva, R., El Marjou, F., Barbazan, J., Krndija, D., Richon, S., Clark, A.G.*, and Vignjevic, D.M.* (2019) Cancer Cells in the Tumor Core Exhibit Spatially Coordinated Migration Patterns. J Cell Sci, 132(6):jcs220277. https://doi.org/10.1242/jcs.220277

Chugh, P.*, Clark, A.G.*, Smith, M.B.*, Cassani, D.A.D., Ragab, A., Roux, P.P., Charras, G., Salbreux, G. and Paluch, E.K. (2017) Actin Cortex Architecture Regulates Cell Surface Tension. Nat Cell Biol, 19(6):689-697. https://dx.doi.org/10.1038/ncb3525

Aizel, K.*, Clark, A.G.*, Simon, A., Geraldo, S., Funfak, A., Vargas, P., Bibette, J., Vignjevic, D.M. and Bremond, N. (2017) A Tuneable Microfluidic System for Long Duration Chemotaxis Experiments in a 3D Collagen Matrix. Lab Chip, 17(22):3851-3861. https://dx.doi.org/10.1039/C7LC00649G

Clark, A.G., and D.M. Vignjevic (2015) Modes of Cancer Cell Invasion and the Role of the Microenvironment. Current Opinion in Cell Biology. 36:13-22. https://doi.org/10.1016/j.ceb.2015.06.004