Photo of Pierfrancesco Pagella

Pierfrancesco Pagella

Associate Professor

Organ (re)generation and genome engineering

My research interests involve the study of the mechanisms underlying organ and cell diversity, and using this knowledge to generate bio-engineered 3D human organs, complete with innervation, vascularization, and immune compartments. To this end, I combine stem cell biology, tissue engineering, organ-on-chip, genomics and proteomics approaches. Strong attention is dedicated to the oro/craniofacial complex, using models such as teeth and cancers of the oral cavity.

two men in labratory,

Claudio Cantù and Pierfrancesco Pagella. Photo credit John Karlsson


Refereed original articles and pre-prints


1. Anna Nordin*, Pierfrancesco Pagella*, Gianluca Zambanini, Claudio Cantù (2023). Exhaustive identification of genome-wide binding events of transcriptional regulators with ICEBERG
BioRxiv (preprint)
*equal contribution/shared first authorship

2. Pierfrancesco Pagella, Simon Söderholm, Anna Nordin, Gianluca Zambanini, Amaya Jauregi Miguel, Claudio Cantù (2023). The time-resolved genomic impact of Wnt/β-catenin signaling. Cell Systems Jul 19;14(7):563-581.e7. doi: 10.1016/j.cels.2023.06.004

3. Simon Söderholm*, Amaia Jauregi-Miguel*, Pierfrancesco Pagella*, Valeria Ghezzi, Gianluca Zambanini, Anna Nordin, Claudio Cantù (2023). Single-cell response to Wnt activation in human embryonic stem cells reveals uncoupling of Wnt target gene expression.
Experimental Cell Research Aug 15;429(2):113646. doi: 10.1016/j.yexcr.2023.113646. Epub 2023 Jun 2.
* equal contribution/shared first authorship

4. Anamaria Balic, Dilara Perver*, Pierfrancesco Pagella*, Hubert Rehauer, Bernd Stadlinger, Andreas E. Moor, Viola Vogel, Thimios A. Mitsiadis (2023). Extracellular matrix remodelling in dental pulp tissue of carious human teeth through the prism of single-cell RNA sequencing. International Journal of Oral Science 2023 Aug 2;15(1):30. doi: 10.1038/s41368-023-00238-z.* equal contribution

5. Anna Nordin, Gianluca Zambanini, Pierfrancesco Pagella, Claudio Cantù (2023). The CUT&RUN Blacklist of Problematic Regions of the Genome. In press @ BMC Genome Biology. Published as preprint: doi: 10.1101/2022.11.11.516118, BioRxiv (preprint)

6. Thimios A. Mitsiadis, Pierfrancesco Pagella, Helder Gomes Rodrigues, Alexander Tsouknidas, Liza L. Ramenzoni, Freddy Radtke, Albert Mehl, Laurent Viriot (2023). Notch signaling pathway in tooth shape variations. Cells 2023 Feb 27;12(5):761. doi: 10.3390/cells12050761.


7. Gianluca Zambanini, Anna Nordin, Mattias Jonasson, Pierfrancesco Pagella, Claudio Cantù (2022). A New CUT&RUN Low Volume-Urea (LoV-U) protocol uncovers Wnt/β-catenin tissue-specific genomic targets. doi: 10.1101/2022.07.06.498999.
Development Nov 10:dev.201124. doi: 10.1242/dev.201124

8. Thimios A. Mitsiadis, Lucia Jimenez-Rojo, Anamaria Balic, Silvio Weber, Paul Saftig, Pierfrancesco Pagella (2022). Adam10-dependent Notch signaling establishes dental epithelial cell boundaries required for enamel formation.
iScience 2022 Sept 16, doi: 10.1016/j.isci.2022.105154.

9. Chai Foong Lai, Juliet Shen, Anamaria Balic, Pierfrancesco Pagella, Martin E. Schwab, Thimios A. Mitsiadis (2022). Nogo-A regulates the fate of human dental pulp stem cells towards osteogenic, adipogenic, and neurogenic differentiation.
Cells Oct 28;11(21):3415. doi: 10.3390/cells11213415.


10. Pierfrancesco Pagella, Bernd Stadlinger, Thimios A. Mitsiadis (2021). Isolation of dental pulp and periodontal cells from human teeth for single-cell RNA sequencing.
STAR Protocols 2, 100953, December 17, 2021. doi: 10.1016/j.xpro.2021.100953.

11. Pierfrancesco Pagella, Laura de Vargas Roditi, Bernd Stadlinger, Andreas E. Moor, Thimios A. Mitsiadis (2021). Notch signaling in the dynamics of perivascular stem cells and their niches. Stem Cells Transl. Med. 2021 Jul 6. doi: 10.1002/sctm.21-0086

12. Pierfrancesco Pagella*, Laura de Vargas Roditi*, Bernd Stadlinger, Andreas E. Moor, Thimios A. Mitsiadis (2021). A Single Cell Atlas of Human Teeth.
iScience May 24(5), doi: 10.1016/j.isci.2021.102405.
* equal contribution/shared first authorship

13. Pierfrancesco Pagella, Cesar Nombela-Arrieta, Thimios A. Mitsiadis (2021). Distinct Expression Patterns of Cxcl12 in Mesenchymal Stem Cell Niches of Intact and Injured Rodent Teeth.
Int. J. Mol. Sc. Mar 16;22(6):3024. doi: 10.3390/ijms22063024.


14. Christian T. Meisel, Pierfrancesco Pagella, Cristina Porcheri, Thimios A. Mitsiadis (2020). Three-dimensional imaging and gene expression analysis upon enzymatic isolation of the tongue epithelium.
Frontiers in Physiology, doi: 10.3389/fphys.2020.00825

15. Pierfrancesco Pagella#, Javier Caton, Christian T. Meisel, Thimios A. Mitsiadis (2020). Ameloblastomas exhibit stem cell potential, possess neurotrophic properties, and establish connections with trigeminal neurons.
Cells. 9(3), 644. doi: 10.3390/cells9030644.
#Co-corresponding author.

16. Pierfrancesco Pagella#, Shayee Miran, Estrela Neto, Ivan Martin, Meriem Lamghari, Thimios A. Mitsiadis (2020). Human dental pulp stem cells exhibit enhanced properties in comparison to human bone marrow stem cells on neurites outgrowth.
FASEB J. 2020 Feb 25. doi: 10.1096/fj.201902482R.
#Co-corresponding author.


17. Lucia Jimenez-Rojo*, Pierfrancesco Pagella*, Hidemitsu Harada, Thimios A. Mitsiadis (2019). Dental epithelial stem cells contribute to mammary gland regeneration and generate milk producing-cells in vivo.
Cells 8 (10) 2019 Oct 22. DOI: 10.3390/cells8101302.
*equal contribution/shared first authorship

18. Amnon Sharir, Pauline Marangoni, Mian Wan, Rapolas Zilionis, Lucia Jimenez-Rojo, Tomas Wald, Jimmy Hu, Kyogo Kawaguchi, Leo Epstein, Kyle Harrington, Pierfrancesco Pagella, Thimios A. Mitsiadis, Chris W. Siebel, Allon M. Klein and Ophir D. Klein (2019). Specific pools of progenitor cells orchestrate homeostasis and regeneration of a continuously growing ectodermal organ.
Nature Cell Biology 21 (9), 1102-1112. Doi: 10.1038/s41556-019-0378-2.

19. Riccardo Monterubbianesi, Mladen Bencun, Pierfrancesco Pagella, Anna Woloszyk, Giovanna Orsini, Thimios A. Mitsiadis (2019). A comparative study of the osteogenic and adipogenic potential of human dental pulp stem cells, gingival fibroblasts and foreskin fibroblasts.
Scientific Reports Feb 11;9(1):1761. doi: 10.1038/s41598-018-37981-x.


20. Thimios Mitsiadis, Pierfrancesco Pagella, Claudio Cantù (2017). Early determination of the periodontal domain by the Wnt-antagonist Frzb/Sfpr3.
Frontiers in Physiology 2017 Nov 21;8:936. doi: 10.3389/fphys.2017.00936. eCollection 2017.

21. Thimios A. Mitsiadis, Pierfrancesco Pagella, Javier Caton, Giovanna Orsini, Lucia Jimenez-Rojo (2017) Monitoring Notch signaling-associated activation of stem cell niches within injured dental pulp.
Frontiers in Physiology 2017 May 30;8:372. doi: 10.3389/fphys.2017.00372. eCollection 2017.

22. Thimios A. Mitsiads, Henry Magloire, Pierfrancesco Pagella (2017): Nerve growth factor (NGF) and p75 neurotrophin receptor (p75NTR) in pathology and regeneration of human teeth. Scientific Reports May 2;7(1):1327. doi: 10.1038/s41598-017-01455-3

23. Claudio Cantù*, Pierfrancesco Pagella*, Tania Darja Shajiei, Dario Zimmerli, Thomas Valenta, George Hausmann, Konrad Basler, Thimios Mitsiadis (2017): A cytoplasmic role of Wnt/B-catenin transcriptional co-factors in tooth development.
Science Signaling 2017 Feb 7;10(465):eaah4598. doi: 10.1126/scisignal.aah4598.
*Equal contribution/shared first authorship


24. Thimios A Mitsiadis, Pierfrancesco Pagella (2016): Expression of nerve growth factor (NGF), TrkA and p75NTR in developing human foetal teeth.
Frontiers in Physiology 2016 Aug 3;7:338. doi: 10.3389/fphys.2016.00338. eCollection 2016.


25. Pierfrancesco Pagella, Shayee Miran, Thimios A. Mitsiadis (2015): Analysis of Developing Tooth Germ Innervation Using Microfluidic Co-culture Devices.
Journal of Visualized Experiments 03/2015; 2015(102). DOI:10.3791/53114.

26. Anna Filatova, Pierfrancesco Pagella, Thimios A. Mitsiadis (2015): Distribution of syndecan-1 protein in developing mouse teeth.
Frontiers in Physiology 01/2015; 5(1). DOI:10.3389/fphys.2014.00518


27. Pierfrancesco Pagella, Estrela Neto, Lucia Jiménez-Rojo, Meriem Lamghari, Thimios A Mitsiadis (2014): Microfluidics co-culture systems for studying tooth innervation.
Frontiers in Physiology 08/2014; 5. DOI:10.3389/fphys.2014.00326.

28. Rebecca Favaro, Irene Appolloni, Serena Pellegatta, Alexandra Badiola Sanga, Pierfrancesco Pagella, Eleonora Gambini, Federica Pisati, Sergio Ottolenghi, Maria Foti, Gaetano Finocchiaro, Paolo Malatesta, Silvia K Nicolis (2014): Sox2 Is Required to Maintain Cancer Stem Cells in a Mouse Model of High-Grade Oligodendroglioma.
Cancer Research 03/2014; 74(6). DOI:10.1158/0008-5472.CAN-13-1942


29. Julia Ahlfeld, Rebecca Favaro, Pierfrancesco Pagella, Hans A Kretzschmar, Silvia Nicolis, Ulrich Schüller (2013): Sox2 Requirement in Sonic Hedgehog-Associated Medulloblastoma. Cancer Research 04/2013; 73(12). DOI:10.1158/0008-5472.CAN-13-0238.


30. Alexandra Frick, Daniel Grammel, Felix Schmidt, Julia Pöschl, Markus Priller, Pierfrancesco Pagella, André O von Bueren, Aurelia Peraud, Jörg-Christian Tonn, Jochen Herms, Stefan Rutkowski, Hans A Kretzschmar, Ulrich Schüller (2012): Proper cerebellar development requires expression of β1-integrin in Bergmann glia, but not in granule neurons.
Glia 05/2012; 60(5). DOI:10.1002/glia.22314


Refereed review articles

1. Thimios Mitsiadis, Pierfrancesco Pagella, Terence D. Cappellini, Moya Meredith Smith (2023). The Notch-mediated circuitry in the evolution and generation of new cell lineages: the tooth model.
Cellular and Molecular Life Sciences 2023 Jun 18;80(7):182. doi: 10.1007/s00018-023-04831-7.

2. Pierfrancesco Pagella*, Alessandro Cordiale*, Guya Diletta Marconi, Oriana Trubiani, Marco Rasponi, Thimios A. Mitsiadis (2021). Bioengineered tooth emulation systems for regenerative and pharmacological purposes. European Cells & Materials 021 May 10;41:502-516. doi: 10.22203/eCM.v041a32. * equal contribution.

3. Pierfrancesco Pagella, Cristina Porcheri, Thimios Mitsiadis (2020). Exploiting teeth as models to study basic features of signaling pathways. Biochemical Society Transactions Nov 6:BST20200514. doi: 10.1042/BST20200514

4. Iolanda Iezzi, Pierfrancesco Pagella, Monica Belmonte-Mattioli, Thimios A. Mitsiadis (2019). The effects of ageing on dental pulp stem cells, the tooth longevity elixir. European Cells & Materials Feb 26;37:175-185. doi: 10.22203/eCM.v037a11.

5. Giovanna Orsini, Pierfrancesco Pagella, Angelo Putignano, Thimios A. Mitsiadis (2018). Novel biological and technological platforms for dental clinical use. Frontiers in Physiology Aug 8;9:1102. doi: 10.3389/fphys.2018.01102. eCollection 2018. Review.

6. Giovanna Orsini, Pierfrancesco Pagella, Thimios A. Mitsiadis (2018). Modern trends in dental medicine: An update for internists. American Journal of Medicine Dec;131(12):1425-1430. doi: 10.1016/j.amjmed.2018.05.042. Epub 2018 Jun 30. Review.

7. Pierfrancesco Pagella, Claudio Cantù, Thimios Mitsiadis (2017): Editorial: Linking dental pathologies and cancer via Wnt signalling. Oncotarget. Nov 3;8(59):99213-99214. doi: 10.18632/oncotarget.22281. eCollection 2017 Nov 21

8. Shayee Miran, Thimios A. Mitsiadis, Pierfrancesco Pagella (2016): Innovative dental stem cell-based research approaches: the future of dentistry. Stem Cells International 2016:7231038. doi: 10.1155/2016/7231038. Epub 2016 Aug 28. Corresponding author.

9. Pierfrancesco Pagella, Estrela Nieto, Meriem Lamghari, Thimios A. Mitsiadis (2015): Investigation of orofacial stem cell niches and their innervation through microfluidic devices. European cells & materials 03/2015; 29.

10. Pierfrancesco Pagella, Lucia Jiménez-Rojo, Thimios A Mitsiadis (2014): Roles of innervation in developing and regenerating orofacial tissues. Cellular and Molecular Life Sciences CMLS 01/2014; 71(12). DOI:10.1007/s00018-013-1549-0.

Chapters in scientific books

1. Pierfrancesco Pagella, Thimios A. Mitsiadis (2020). Analysis of tooth innervation in microfluidic co-culture devices. In: Craniofacial Biology. “Methods in Molecular Biology” series. C. Kioussi (ed) Springer, Humana Press, USA.

2. Lucia Jiménez-Rojo, Zoraide Granchi, Anna Woloszyk, Anna Filatova, Pierfrancesco Pagella, Thimios A. Mitsiadis (2014). Regenerative Dentistry: Stem Cells meet Nanotechnology. In: Horizons in Clinical Nanomedicine. Pan Stanford Publishers, USA (ed) pp:255-286.


Associate professor,
Department of physics, chemistry and biology, Division of biophysics and bioengineering, Linköping University, Linköping, Sweden

Postdoctoral research Fellow
, Wallenberg Center for Molecular Medicine (WCMM) and Department of Biomedical and Clinical Sciences, Division of Molecular Medicine and Virology, Linköpings University, Linköping, Sweden

Lecturer/Senior Scientist
 (Oberassistent), Institute of Oral Biology, University of Zurich, Zurich, Switzerland.

Visiting scientist
, Weill Cornell Medical College, New York City, NY, U.S.A.

Postdoctoral Fellow
, Institute of Oral Biology, University of Zurich, Zurich, Switzerland.

Visiting student
, Center of Biomedical Engineering (INEB), University of Porto, Porto, Portugal.

. Molecular Life Sciences PhD Program, ETH/University of Zurich. Institute of Oral Biology, University of Zurich, Zurich, Switzerland.

Research Associate
, Group Prof. S. K. Nicolis, Department of Biology and Biotechnologies, Università degli Studi di Milano-Bicocca, Milan, Italy.

Visiting Student
, Institute for Neuropathology and Prion Research, Ludwig-Maximilians-University, Munich, Germany.

. In Biology (110/110 cum laude), Università degli Studi di Milano Bicocca, Milan, Italy.

. In Biological Sciences (110/110), Università degli Studi di Milano-Bicocca, Milan, Italy.

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