![Immunofluorescent staining of E14.5 (embryonic day of development 14.5) mouse lower molar, from [Pagella et al. 2021, Int J Mol Sci]](https://cdn.myportfolio.com/0dd9a87c-e8e4-4ce7-990a-591dc121a57b/6ff45791-55a2-4991-915d-3dcfe93be4c7_rw_1920.jpg?h=e2f638aca4d51bb71e7da9654265c3cc)
Immunofluorescent staining of E14.5 (embryonic day of development 14.5) mouse lower molar, from [Pagella et al. 2021, Int J Mol Sci]
![Toluidine blue staining of ground sections of a non-decalcified mouse upper incisor, from [Cantù, Pagella et al. 2017, Science Signaling] - selected as Cover photo](https://cdn.myportfolio.com/0dd9a87c-e8e4-4ce7-990a-591dc121a57b/b3df897c-150f-4928-8705-0f44505536d3_rw_1920.jpg?h=bdd44bbd77af95b6e17b52750120a6f2)
Toluidine blue staining of ground sections of a non-decalcified mouse upper incisor, from [Cantù, Pagella et al. 2017, Science Signaling] - selected as Cover photo
![Interaction between trigeminal neurons (green) and human mesenchymal stem cells (red) - from [Pagella et al. 2021, FASEB J]](https://cdn.myportfolio.com/0dd9a87c-e8e4-4ce7-990a-591dc121a57b/4e885428-4de0-4834-8594-caa6c553f040_rw_1920.jpg?h=5229f95f2bc9f97bddcf8b60182dd26b)
Interaction between trigeminal neurons (green) and human mesenchymal stem cells (red) - from [Pagella et al. 2021, FASEB J]
4-channels high-resolution confocal imaging of LS8 mouse cells (ameloblastic cell line)
![Interaction between trigeminal neurons (red) and human ameloblastoma cells (grey) - from [Pagella et al. 2021, Cells]](https://cdn.myportfolio.com/0dd9a87c-e8e4-4ce7-990a-591dc121a57b/d17ccfab-a9b9-4368-aa13-b1c5f4280dbb_rw_1200.jpg?h=347456f35a7974bbc8688ad2c1a89408)
Interaction between trigeminal neurons (red) and human ameloblastoma cells (grey) - from [Pagella et al. 2021, Cells]
![Whole mount immunofluorescent staining showing the 3D distribution of vasculature (laminin, red) and CXCL12-positive cells (green) in the pulp of a mouse molar - from [Pagella et al. 2021, Int J Mol Sci]](https://cdn.myportfolio.com/0dd9a87c-e8e4-4ce7-990a-591dc121a57b/e32472da-ffa2-45c5-a887-9407f2f84cea_rw_1920.jpg?h=a3362406db2cbf027451710047005905)
Whole mount immunofluorescent staining showing the 3D distribution of vasculature (laminin, red) and CXCL12-positive cells (green) in the pulp of a mouse molar - from [Pagella et al. 2021, Int J Mol Sci]
My underlying, driving interest, from my undergraduate studies throughout my research career, has been the correlation between the information contained in the genome and the extremely complex series of events that it encodes during development, and to exploit this information to help regenerate human organs. To pursue this passion, I embarked in several multidisciplinary projects.
The time- and cell-specificity of chromatin dynamics upon signaling pathway activation
Since April 2021, I focused my attention on the correlation between protein/DNA interactions, chromatin accessibility, and their outcome in larger cellular processes. In particular, I focused my attention on the Wnt signaling pathway. The Wnt/β-catenin-driven transcriptional response is involved in virtually all cellular processes during development and homeostasis while its deregulation causes human disease 1. While many studied provided us with substantial knowledge about how Wnt works and concerning groups of Wnt target genes in different contexts, two outstanding questions remain unanswered. The first concerns time: it is not known whether β-catenin associates with its targets simultaneously or in a time-dependent fashion. The second question regards how the Wnt/β-catenin cascade modulates chromatin behavior: to date, there exists no comprehensive genome-wide annotation of changing chromatin patterns upon pathway activation. This is important, as shifts in chromatin patterns might underlie how different cells promote diverging gene expression programs in response to Wnt. To address the first question, we leveraged on our novel CUT&RUN-LoV-U (Cleavage Under Targets & Release Using Nuclease - Low Volume - Urea) protocol 2 to establish the full sets of β-catenin target genes detectable over time in two paradigmatic, Wnt-responsive human cell types: human embryonic kidney cells (HEK293T) and human embryonic stem cells (hESCs). This approach allowed us to establish that β-catenin repositions to different genomic loci along stimulation time, showing that a definition of Wnt target genes must take into account the time-dimension. Moreover, β-catenin physical targets are largely cell-type specific, as only a subset of them are present across the examined contexts. Second, to mechanistically understand the causal relation between β-catenin binding and the induced genetic programs, we analyzed how this pathway orchestrates the chromatin dynamics genome-wide across defined time points. We found that human embryonic stem cells (hESCs) respond to Wnt/β-catenin activation by progressively shaping their chromatin accessibility profile in a manner that is consistent with their gradual acquisition of a mesodermal identity: differentiation genes loci open over time, while pluripotency ones close. We refer to this genomic response as plastic. On the other hand, human embryonic kidney cells (HEK293T), which are known to be highly responsive to Wnt activation, appear more resistant to a long-term Wnt/β-catenin-driven change in cell identity. In this context, the chromatin displays a temporary opening of relevant regions at 4 hours after stimulation, followed by a re-establishment of its pre-stimulation state: we define this transient response as elastic. Finally, by using genetic tools and enzymatic inhibitors, we demonstrated that the transient chromatin opening mechanistically requires β-catenin together with histone acetyltransferase and deacetylase enzymatic activities, unearthing a previously overlooked chromatin pioneering function of β-catenin. We propose that the plastic and elastic responses represent modalities of genomic behaviors induced by Wnt/β-catenin that underlie how this signaling pathway can elicit radically divergent responses depending on the cellular context 3.
Cell identity and cell fate decision in homeostasis and regeneration of teeth and ectodermal organs
During my years at the University of Zurich, I drove several projects aimed to characterize in detail the cellular composition of mouse and human and ectodermal organs, and the contribution of the various cell populations in homeostasis and regeneration. One of these projects resulted in the publication of the first, comprehensive single cell atlas of human teeth 4. Our study identified great cellular heterogeneity in the dental pulp and the periodontium (the tissue that anchors teeth to the surrounding alveolar bone). Unexpectedly, we found that the molecular signatures of dental pulp and periodontal stem cell populations were very similar, while the cellular and molecular composition of their respective microenvironments strongly diverged. Our findings suggest that the microenvironmental specificity is the potential source for the well-known functional differences between these highly similar stem cell populations located in the various tooth compartments. We further observed that both dental pulp and periodontal mesenchymal stem cells express NOTCH3, and that NOTCH3 expression is downregulated upon their differentiation. We observed that in the dental pulp and the periodontium these cells are localized mostly in perivascular niches, both in human and in mice. We further demonstrated that these cells are important for the response to traumatic injuries in vivo in a transgenic mouse model, and that their behavior could be modulated by differential abundance of Notch-ligands coming from their microenvironments 5. In a parallel line of research, I contributed to investigate the relationship between different ectodermal appendages (EAs), in particular between teeth and mammary glands. Based on the known, close evolutionary and developmental relationship between EAs, we investigated whether dental epithelial stem cells would be able to give rise to a functional mammary gland epithelium after its depletion. We indeed hypothesized that stem cells from teeth might be easily reprogrammed by the microenvironment of another EAs, thanks to their developmental and evolutionary proximity. Moreover, we hypothesized that teeth might be more closely related to a hypothetical, ancestral EAs (being present in all vertebrates’ subphyla) than mammary glands (present only in mammals), and therefore be more responsive to signals deriving from other EAs. I therefore transplanted dental epithelial stem cells (DESCs), isolated from the continuously growing mouse incisor, together with mammary epithelial cells into the mammary stroma, and we observed the formation of chimeric ductal epithelial structures. In these mammary ducts, DESCs adopted all the possible mammary fates including milk-producing alveolar cells. We then transplanted DESCs without mammary epithelial cells, and DESCs developed branching rudiments and cysts. Thus, using this approach we could demonstrate that DESCs can undergo not only dental morphogenesis and differentiation, but also branching morphogenesis (typical of glands) and mammary gland-specific-differentiation simply under the effect of the right microenvironment 6.
Non-canonical functions of signaling pathways and molecules in the development of teeth and ectodermal appendages
During my PhD and my postdoctoral studies, a common theme has been the investigation of non-canonical functions of signaling molecules. We first focused on the study of non-neuronal-roles of molecules classically studied for their function during neural development and regeneration. First, we investigated the role of Nogo-A in the development and the regeneration of teeth in transgenic mouse models. Nogo-A is a fundamental actor of nervous system development, physiology, and regeneration, and the target of ongoing clinical trials. However, I detected Nogo-A expression in dental cells themselves well before tooth innervation, and observed that such expression was strictly correlated with their differentiation status – i.e. high in the dental epithelial stem cell niche, and in terminally-differentiated ameloblasts – the highly specialized cells that secrete dental enamel, low in progenitor cells. We showed that the deletion of Nogo-A in the dental epithelium of transgenic mice leads to the formation of defective enamel, and that this phenotype is associated with overexpression of clusters of genes involved in cell differentiation and enamel production. We further demonstrated that Nogo-A here is mostly localized intracellularly, where it directly interacts with molecules important for gene expression regulation 7. We then studied the expression and potential role of nerve growth factor (NGF) and its receptors P75 and TrkA in tooth development and pathology. We observed that NGF, P75 and TrkA are expressed in human dental tissues well before the onset of tooth innervation, suggesting innervation-independent roles 8. Indeed, the expression of NGF and its receptor TrkA was strictly correlated with the onset of cytodifferentiation, and then downregulated at the end of the development period. We further observed that, upon injury, NGF expression is strongly upregulated immediately beneath the damaged area in humans, and that this NGF overexpression is both associated with formation of mineralized matrix (a reparative response) and increased innervation of the injured area 9.
In parallel, we studied how specific members of the Wnt signaling pathway affect tooth development. Bcl9 and Bcl9l are tissue-specific β-catenin transcriptional cofactors. In the nucleus, Bcl9 and Bcl9l simultaneously bind β-catenin and the transcriptional activator Pygo2 to promote the transcription of Wnt target genes. We showed however that, during tooth formation, Bcl9, Bcl9l, and Pygo2 localized mainly to the cytoplasm of the epithelial-derived ameloblasts, the cells responsible for enamel production. In ameloblasts, Bcl9 interacted with proteins involved in enamel formation and proteins involved in exocytosis and vesicular trafficking. Conditional deletion of both Bcl9 and Bcl9l or both Pygo1 and Pygo2 in mice produced teeth with defective enamel. Overall, our data revealed that these proteins, originally considered solely β-catenin transcriptional cofactors, function in odontogenesis through a previously uncharacterized cytoplasmic mechanism, revealing that they have roles beyond that of transcriptional cofactors 10.
Development of microfluidic co-culture systems for the emulation of mouse and human tissues.
To improve my ability to investigate complex organ dynamics, I pursued the optimization of organ-on-chip co-culture systems for the emulation of mouse and human organs in vitro. We first validated these devices by modeling innervation of developing teeth in vitro, demonstrating that co-culture of whole tooth germs and trigeminal ganglia in microfluidic devices faithfully recapitulates in vivo tooth innervation 11. We then used microfluidic co-culture devices to study the interaction between trigeminal nerves, the main responsible of face and tooth innervation, and different populations of human mesenchymal stem cells, namely dental pulp stem cells and bone marrow stromal cells. We demonstrated that dental pulp stem cells have a significantly higher neurotrophic potential compared to bone marrow stromal cells, as they elicit not only the growth of longer trigeminal axons, but also support the creation of active axonal networks 12. We further used this microfluidic co-culture system to study the innervation of oral cancer, namely ameloblastoma. Ameloblastomas are locally aggressive cancers originating from the dental epithelium, a tissue which is not innervated in physiological conditions. We however showed that human ameloblastomas are innervated in human patients. We therefore investigated whether ameloblastoma cancer cells themselves are able to attract nerve fibers. We thus isolated and characterized cells from human ameloblastomas and co-cultured them with trigeminal ganglia. We demonstrated that ameloblastoma cells indeed acquired neurotrophic properties, and that trigeminal axons form synaptic contacts with them, suggesting a functional role for innervation in ameloblastoma onset or progression 13.
References:
1. Nusse R, Clevers H. Wnt/β-Catenin Signaling, Disease, and Emerging Therapeutic Modalities. Cell. 2017;169(6):985-999. doi:10.1016/j.cell.2017.05.016
2. Zambanini G, Nordin A, Jonasson M, Pagella P, Cantù C. A New CUT & RUN Low Volume-Urea ( LoV-U ) protocol uncovers Wnt / beta-catenin tissue-specific genomic targets. bioRxiv. 2022;2022:1-12. doi:10.1101/2022.07.06.498999
3. Pagella P, Söderholm S, Nordin A, Zambanini G, Jauregi-Miguel A, Cantù C. Time-resolved analysis of Wnt-signaling reveals β -catenin temporal genomic repositioning and cell type-specific plastic or elastic chromatin responses. bioRxiv. 2022;2022:1-25.
4. Pagella P, de Vargas Roditi L, Stadlinger B, Moor AE, Mitsiadis TA. A single-cell atlas of human teeth. iScience. 2021;24(5):102405. doi:10.1016/J.ISCI.2021.102405
5. Pagella P, de Vargas Roditi L, Stadlinger B, Moor AE, Mitsiadis TA. Notch signaling in the dynamics of perivascular stem cells and their niches. Stem Cells Transl Med. 2021;10(10):1433-1445. doi:10.1002/SCTM.21-0086
6. Jimenez-Rojo L, Pagella P, Harada H, Mitsiadis TA. Dental Epithelial Stem Cells as a Source for Mammary Gland Regeneration and Milk Producing Cells In Vivo. Cells 2019, Vol 8, Page 1302. 2019;8(10):1302. doi:10.3390/CELLS8101302
7. Pagella P. The Role of Nogo-A in tooth development and regeneration. Published online 2016.
8. Mitsiadis TA, Pagella P. Expression of nerve growth factor (NGF), TrkA, and p75NTR in developing human fetal teeth. Front Physiol. 2016;7(AUG):338. doi:10.3389/FPHYS.2016.00338/BIBTEX
9. Mitsiadis TA, Magloire H, Pagella P. Nerve growth factor signalling in pathology and regeneration of human teeth. Sci Reports 2017 71. 2017;7(1):1-14. doi:10.1038/s41598-017-01455-3
10. Cantù C, Pagella P, Shajiei TD, et al. A cytoplasmic role of Wnt/b-catenin transcriptional cofactors Bcl9, Bcl9l, and Pygopus in tooth enamel formation. Sci Signal. 2017;10(465). doi:10.1126/SCISIGNAL.AAH4598/SUPPL_FILE/AAH4598_SM.PDF
11. Pagella P, Neto E, Jiménez-Rojo L, Lamghari M, Mitsiadis TA. Microfluidics co-culture systems for studying tooth innervation. Front Physiol. 2014;5 AUG:326. doi:10.3389/FPHYS.2014.00326/ABSTRACT
12. Pagella P, Miran S, Neto E, Martin I, Lamghari M, Mitsiadis TA. Human dental pulp stem cells exhibit enhanced properties in comparison to human bone marrow stem cells on neurites outgrowth. FASEB J. 2020;34(4):5499-5511. doi:10.1096/FJ.201902482R
13. Pagella P, Catón J, Meisel CT, Mitsiadis TA. Ameloblastomas Exhibit Stem Cell Potential, Possess Neurotrophic Properties, and Establish Connections with Trigeminal Neurons. Cells 2020, Vol 9, Page 644. 2020;9(3):644. doi:10.3390/CELLS9030644
Publications list
Original Articles
2023
Pierfrancesco Pagella, Simon Söderhölm, Anna Nordin, Gianluca Zambanini, Amaya Jauregi Miguel, Claudio Cantù (2022). The time-resolved genomic impact of Wnt/b-catenin signaling. Accepted, in press @ Cell Systems. Published as preprint: Time-resolved analysis of Wnt-signaling reveals β-catenin temporal genomic repositioning and cell type-specific plastic or elastic chromatin responses. doi: 10.1101/2022.08.05.502932. BioRxiv (preprint)
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. Accepted, in press @ Experimental Cell Research. Published as preprint: Doi: 10.1101/2023.01.11.523587, BioRxiv (preprint)
Anamaria Balic*, Dilara Perver*, Pierfrancesco Pagella*, Hubert Rehauer, Bernd Stadlinger, Andreas E. Moor, Viola Vogel, Thimios A. Mitsiadis (2023). Single-cell transcriptomics analysis reveals extracellular matrix remodelling in carious human dental pulp. Second round of revision @ International Journal of Oral Science. Published as preprint: doi: 10.1101/2023.02.15.528696, BioRxiv (preprint)
Anna Nordin, Gianluca Zambanini, Pierfrancesco Pagella, Claudio Cantù (2023). The CUT&RUN Blacklist of Problematic Regions of the Genome. Second round of revision @ BMC Genome Biology. Published as preprint: doi: 10.1101/2022.11.11.516118, BioRciv (preprint)
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.
2022Gianluca Zambanini, Anna Nordin, Mattias Jonasson, Pierfrancesco Pagella, Claudio Cantù (2022). A New CUT&RUN Low Volume-Urea (LoV-U) protocol uncovers Wnt/b-catenin tissue-specific genomic targets. doi: 10.1101/2022.07.06.498999 BioRxiv (preprint) – in revision @ Development
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.
Thimios A. Mitsiadis, Lucia Jimenez-Rojo, Anamaria Balic, Silvio Weber, Paul Saftig, Pierfrancesco Pagella (2022). Adam10-dependent Notch signalling establishes dental epithelial cell boundaries required for enamel formation. iScience. 2022 doi:10.1016/j.isci.2022.105154.
2021
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.
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 Translational Medicine. 2021 Jul 6. doi: 10.1002/sctm.21-0086
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.
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. International Journal of Molecular Sciences. Mar 16;22(6):3024. doi: 10.3390/ijms22063024.
2020
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.
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.
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 Journal. 2020 Feb 25. doi: 10.1096/fj.201902482R. Co-corresponding author.
2019
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.
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.
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.
2017
Thimios Mitsiadis, Pierfrancesco Pagella, Claudio Cantù (2017). Early determination of the periodontal domain by the Wnt-antagonist Frzb/Sfpr3. Frontiers in Physiology 8: 936 (doi: 10.3389/fphys.2017.00936)
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 04/2017, 8(372).
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 04/2017, 7(1327).
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 02/2017, 10(465). *Equal contribution.
2016
Thimios A Mitsiadis, Pierfrancesco Pagella (2016). Expression of nerve growth factor (NGF), TrkA and p75NTR in developing human foetal teeth. Frontiers in Physiology 08/2016; 7(338).
2015
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.
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
2014
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.
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
2013
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.
2012
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
Review articles
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.
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
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.
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.
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.
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
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.
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.
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.
Book chapters
Thimios A. Mitsiadis, Pierfrancesco Pagella (2021). The Versatile Roles of Nerve Growth Factor in Neuronal Attraction, Odontoblast Differentiation, and Mineral Deposition in Human Teeth. In: Recent Advances in NGF and Related Molecules, “Advances in Experimental Medicine and Biology” series. L. Calzà, L. Aloe, L. Giardino (ed) Springer, Humana Press, USA. 2021;1331:65-75. doi: 10.1007/978-3-030-74046-7_6.
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. 2020;2155:99-106. doi: 10.1007/978-1-0716-0655-1_8.
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.