The Cantù Lab - Genome Regulation in Development and Disease

Claudio Cantu's research at WCMM

THE MISSION: The Cantù Lab at LiU is focused on one important goal: to discover the mechanisms of genome regulation that drive cell differentiation and specialization during embryonic development.

In the Cantù lab we make use of mouse genetics, high-throughput biochemical approaches – our favorite at the moment is CUT&RUN – to discover the composition of signals and the protein “arsenal” that, in each cell type, allows the activation of the correct genes.

Our experimental efforts are focused on the so-called ‘Wnt/β-catenin signalling pathway’, a molecular cascade important for virtually all aspects of development, and whose deregulation causes human malformations and several forms of aggressive cancers, among which colorectal cancer.

OUR VALUES:

CREATIVITY: There are questions about reality that we wish to answer – by whatever means. We explore ideas, try to generate new tools, and embrace failure to become more inventive.

FANTASY: Creative ideas and motivation come from a place of quiet but enthusiastic imagination. We hope that we will never lose the quality that children have to dream with eyes wide open.

COLLEGIALITY: We share one mission and work together to accomplish it. Others’ success is also ours.

FREEDOM: We feel free to experiment new crazy ideas. But also to criticize them if we feel that they can be improved. And a good experiment never fails into revealing a piece of reality, even when our hypothesis is wrong.

TRUSTWORTHINESS: We do our best such that what we do, however small, can be relied upon. We live our values such that our coworkers and collaborators can trust we are doing our best.

Publications

Highlighted publications

Cover of publication 'Cover image for Cell Systems.'
Pierfrancesco Pagella, Simon Söderholm, Anna Nordin, Gianluca Zambanini, Valeria Ghezzi, Amaia Jauregi Miguel, Claudio Cantù (2023)

CELL SYSTEMS , Vol.14 , s.563-581.e7 Continue to DOI

Cover of publication 'Cover image for Genome Biology.'
Anna Nordin, Gianluca Zambanini, Pierfrancesco Pagella, Claudio Cantù (2023)

Genome Biology , Vol.24 Continue to DOI

Cover of publication 'Cover to Science Direct.'
Simon Söderholm, Amaia Jauregi Miguel, Pierfrancesco Pagella, Valeria Ghezzi, Gianluca Zambanini, Anna Nordin, Claudio Cantù (2023)

Experimental Cell Research , Vol.429 Continue to DOI

Cover of publication 'Cover of scientific magazine about biology and stem cells.'
Gianluca Zambanini, Anna Nordin, Mattias Jonasson, Pierfrancesco Pagella, Claudio Cantù (2022)

Development , Vol.149 Continue to DOI

Cover of publication 'Cover for publication by Simon Söderholm and Claudio Cantù.'
Simon Söderholm, Claudio Cantù (2021)

Wiley Interdisciplinary Reviews: Systems Biology and Medicine , Vol.13 Continue to DOI

Most recent publications from DiVA

2024

Anna Nordin, Pierfrancesco Pagella, Gianluca Zambanini, Claudio Cantù (2024) Exhaustive identification of genome-wide binding events of transcriptional regulators Nucleic Acids Research Continue to DOI
Giulia Pizzolato, Lavanya Moparthi, Pierfrancesco Pagella, Claudio Cantù, Padraig D´arcy, Stefan Koch (2024) The tumour suppressor p53 is a negative regulator of the carcinoma-associated transcription factor FOXQ1 Journal of Biological Chemistry, Vol. 300, Article 107126 Continue to DOI

2023

Pierfrancesco Pagella, Simon Söderholm, Anna Nordin, Gianluca Zambanini, Valeria Ghezzi, Amaia Jauregi Miguel, Claudio Cantù (2023) The time-resolved genomic impact of Wnt/(3-catenin signaling CELL SYSTEMS, Vol. 14, p. 563-581.e7 Continue to DOI
Anna Nordin, Gianluca Zambanini, Pierfrancesco Pagella, Claudio Cantù (2023) The CUT & RUN suspect list of problematic regions of the genome Genome Biology, Vol. 24, Article 185 Continue to DOI
Lovisa Örkenby, Signe Skog, Helen Ekman, Alessandro Gozzo, Unn Örtegren Kugelberg, Rashmi Ramesh, Srivathsa Magadi, Gianluca Zambanini, Anna Nordin, Claudio Cantù, Daniel Nätt, Anita Öst (2023) Stress-sensitive dynamics of miRNAs and Elba1 in Drosophila embryogenesis Molecular Systems Biology, Vol. 19, Article e11148 Continue to DOI

Research Group

Image of a group of people.
Members of The Cantù Lab at the end of 2023.

Members of The Cantù Lab

Claudio Cantù to the left together with members of the lab.

Claudio Cantù

Claudio Cantù - Bio sketch

I obtained PhD training at the University of Milano-Bicocca in the lab of Prof. Antonella Ronchi and Prof. Sergio Ottolenghi, focusing on the factors that drive the regulation of human globin genes transcription in erythroid cells, and how fetal genes are replaced by adult ones, a process known as “globin switching”. A summer stay in Oxford (UK) in the lab or Prof. Tariq Enver at the Weatherall Institute of Molecular Medicine, working 24/7 with Dr. Cristina Fugazza, allowed me to identify and focus on one specific protein, the transcription factor SOX6. In 2011 I changed field and joined the developmental genetics lab of Prof. Dr. Konrad Basler, at the University of Zurich, Switzerland, and started an ambitious research program in which I applied the genetic knowledge obtained in Drosophila melanogaster to study mammalian genetics.

I generated a series or mutant mouse strains that allowed me to dissect several aspects of how the Wnt pathway is transduced in different cell types during development. Here, many persons shaped my scientific growth in addition to Koni Basler, from George Hausmann, to Tomas Valenta, Dario Zimmerli, Nick Doumpas, Christian Mosimann and Erich Brunner – to mention a few.

My efforts generated a series of scientific discoveries that not only revealed how little was known about signaling pathways, but also shown how these mechanisms are employed or hijacked by cancer cells. In February 2018, I moved from Switzerland to Sweden, when I was awarded a generous research starting grant from the Knut och Alice Wallenberg Foundation. This allowed me to build a research group focused on the mechanisms via which cells influence each other´s genomes during development.

Simon Söderholm

Simon Söderholm - Bio sketch

Simon is from a smaller town called Söderköping located in Östergötland County, Sweden. He started his academic journey studying environmental science at Linköping University, Campus Norrköping. After receiving a bachelor’s degree, Simon then worked in the industry as an environment- and quality technician. After a number of years, he moved to Linköping and decided to start studying again, this time Chemical Biology, which was more in line with his interest in the molecular aspects of biology. During his Master’s he also went into the world of computational biology and bioinformatics, which was – he feels – a natural step giving his strong interest and experience in programming. After that, he worked as a research assistant until he started his doctoral training in the Claudio Cantù lab. 
The overall aim of his work, common to the aim of the group as a whole, revolves around studying tissue-specific properties of Wnt signaling, using genome-wide sequencing technologies and computational methods.

The long-term goal is to better understand how this seemingly linear process is able to act in such a versatile manner, knowledge that could improve our ability to treat diseases such as cancer.

Outside of work, Simon´s hobbies include writing novels, programming games and taking care of collections of coins and fossils/minerals.

Claudio Cantú and Simon Söderholm discuss the results.Claudio Cantù (left) and Simon Söderholm (right) discuss the implications of a new discovery. Simon Söderholm points to the identification of a small region, within the vast genome, that contains the small group of genes identified in the new study, which is important for the ability of embryonic stem cells to decide whether to divide or become specialized cells. Simon combined experimentation with sophisticated informatic analyses to identify the behaviour of these genes. Photo credit John Karlsson

Anna Nordin

Anna Nordin - Bio sketch

Anna grew up in the United States and has a bachelor's degree in Biomedicine from the University of Skövde. She took her master's degree at Linköping's University in the Experimental and Medical Biosciences program in 2022. She is now a PhD student in the lab of Claudio Cantù, researching the interplay between Wnt signaling and chromatin structure during development and disease.

Anna is interested in how chromatin and epigenetics are involved in cell behavior, and how this can be implicated in disease. In the lab she is looking into how the Wnt signaling pathway affects the three-dimensional structure of the genome, using both wet-lab and bioinformatic methods.

Anna Nordin, Master's student at BKV and connected to Claudio Cantù's research group, works in the lab.Anna Nordin, member of the Cantù Lab. Anna is an expert in Transcription Factors profiling and Genomic 3D organization. Photo credit John Karlsson

 

Tamina Weiss 

Tamina Weiss - Bio sketch

Tamina Weiss grew up in the south of Germany and holds a bachelor’s degree in molecular medicine from the Medical University in Innsbruck. Shortly after she started the double degree program. During her studies in Biomedicine at Linköping University she joined Markus Heilig group to investigate the neural circuitry of a neuronal subpopulation of the rat central amygdala that are functionally linked to compulsive behaviour in alcohol dependent rats. Driven by her interest in how to model complex systems in vitro she studied tissue engineering and regenerative medicine at the University of Applied Sciences in Vienna. Via a short stay at Karolinska Insitutet, to learn about iPS reprogramming and 2D neuronal differentiation systems, she joined the Anna Falk group at Lund University for her thesis project. She developed 3D forebrain organoids from an individual diagnosed with autism to study the role of a presynaptic adhesion molecule in early neurodevelopment.

Her interest in the capacity of cells to self-organize into highly organized structures and how this is regulated by precisely timed pathways, specifically the role of WNT in different tissues and during different stages in development, and gene dynamics is what motivated her to join Claudio Cantù Lab in the scope of a preparatory research course.

Woman on a bike out in nature.Tamina Weiss.

Yorick van de Grift

Yorick van de Grift - Bio sketch

Yorick van de Grift grew up in the Netherlands. He studied biomedical sciences at the University of Utrecht from 2010-2016. For his master program (Cancer, Stem cells, and Developmental biology) he joined the labs of Dr. Hugo Snippert to investigate Colorectal organoids and Prof. Dr. Roel Nusse to study WNT signalling in hepatocytes. After obtaining his master’s degree, he joined the lab of Dr. Renée van Amerongen at the University of Amsterdam to study WNT-responsive stem cells and the epigenetic regulation of their niche ligands. Here he characterized and imaged novel mouse models to study WNT-dependent stem cell dynamics in vivo and in vitro and addressed a particularly understudied aspect of stem cell biology, focussing on the niche cells and how expression of WNT ligands is regulated.

This project focussed on the mammary gland, where it is known that hormone levels are important for the activation of WNT ligands, however, how these systemic hormone levels are converted by niche cells to a localised WNT signal is still unclear. To address this question, he probed the chromatin structure and protein-DNA interactions using CRISPR/Cas9, (single cell) next-generation sequencing techniques and computational methods to identify enhancer elements and novel transcription factors that drive WNT ligand expression in the mammary gland. In November 2023 he joined the lab of Claudio Cantù to investigate the role of β-catenin and its transcriptional complex in tissue and cell type-specific properties of WNT signalling.

Alumni

Previous members of The Cantù Lab

Salome Brütsch

Image of Salome out skiing.Salome Brütsch. Salome was born in a small town close to Zurich. She studied biology at the University of Zurich and performed her Master thesis in the Konrad Basler lab under the supervision of Claudio Cantù working on TBX3 and BCL9, both proteins involved in Wnt signaling. After the Master’s degree Salome decided to dive into a new topic and started her PhD in the lab of Sabine Werner in a small subgroup led by Mattia Bordoli. She studied VLK/Pkdcc, the first and so far only known secreted tyrosine kinase, in the mouse model and observed perinatal lethality upon mesenchyme-specific deletion of VLK/Pkdcc. The project initially outlined for wound healing went to a completely different direction. Salome wanted to find out why the mesenchyme-specific VLK/Pkdcc knockout is lethal and therefore she became the first person in the Werner lab that studied a protein in the context of embryonic lung development.

After completion of her doctoral studies Salome joined the Cantù lab in February 2023 for a short postdoctoral fellowship to work again on the interesting transcription factor TBX3.

Outside of work Salome enjoys to do sports, on weekends she loves to spend time in nature, hiking, road cycling and trying to cross country ski. She also enjoys having good conversations with friends accompanied by a good wine. During the week you can find her in various group fitness classes and at home relaxing through reading, listening to podcasts and doing Makrameh for all the baby plants she tries to raise.

Michael Gerstorfer

Michael Gerstorfer, previous member of the Cantù Lab.Michael Gerstorfer. Michael is a cellular biologist who has focused his academic studies and work towards investigating highly spatially organized in vitro cellular constructs, like gastruloids and organoids, and their potential to act as medical screening, research and eventually treatment tools. Michael received a Bachelor’s degree in Biomedical Engineering from the UAS Technikum Vienna. 

Later, he went on to do a double Master’s degree in Cell and Tissue Engineering from the UAS Technikum Vienna and Medical Sciences from Linköping University. During his thesis, Michael used gastruloids as research device to investigate the role of Wnt signalling in early embryonic development in the group of Claudio Cantù. Michael is currently working at the CeMM Research Institute in Vienna investigating gastric organoids as a screening tool for esophageal and gastric diseases in the lab of Georg Busslinger.

Valeria Ghezzi

Portrait image of Valeria Ghezzi. Valeria worked as a Research preparatory course student in Claudio Cantù's lab. She graduated in Biology, with a Molecular Biology curriculum, at the University of Milano-Bicocca, Italy. Her main interest is understanding the molecular mechanisms behind developmental diseases.

Amaya Jauregi Miguel

Photo credit Emma Busk Winquist

Patricia Johansson

Patricia Johansson, alumnus of Claudio Cantù's research group.Patricia Johansson. Patricia started her career in the Cantù lab as a Master´s student in January 2019, and stayed for about 2 years as a Research Assistant after her studies. In the group, she got a lot of freedom to explore new and fascinating techniques and help establish them in the lab. This ranged from stem cell work and proteomics with Mass Spectrometry. Currently, she has chosen to set her eyes on research connected to product development and is working at Fujirebio Diagnostic AB with development of in vitro-diagnostic products.

Mattias Jonasson

Mattias Jonasson, previous member of the Cantù Lab.Mattias Jonasson in the lab. Mattias was awarded his MSc in Molecular Biology by Umeå University. Drawn to the field of developmental biology, he joined the Cantù lab as a research engineer in 2018. Chromatin biology soon caught his interest, leading him to set up CUT&RUN to study transcription factor occupancy in development and cancer. Apart from hands-on lab work, he also found fulfillment in supervising undergraduate students; all of whom he remembers with great pride. In 2021, Mattias left to join the lab of Dr. Elly Tanaka (IMP, Vienna) as a PhD student. He now studies how fibroblast plasticity determines wound healing outcomes and regenerative potential of different species.

Alessandro Mattia

Portrait picture of a man in front of a yellow background.Alessandro Mattia. Alessandro was born in Milan, Italy, and obtained his Master degree in Medical and Pharmaceutical Biotechnology at the University of Pavia, where he developed interest for genome integrity and the role of chromatine in tumorigenesis. Soon after defending his thesis, Alessandro joined the Cantù Lab to improve his laboratory skills and his critical sensibility, before starting a PhD. At the moment, he is working on TBX3 and its potential function in colorectal cancer metastasis.

In his sparetime, Alessandro takes care of his plants, and has a strong passion for architecture and photography, reason why it is very likely to find him looking up to get the perfect shot.

Position: Postgraduate Erasmus student
E-mail: alemattia3197@gmail.com

Vittorio Monticelli

Vittorio Monticelli, previous member in the Cantù Lab.Vittorio Monticelli. Vittorio studied Biomedical Laboratory Techniques at the University of Foggia, Italy, and he received his Degree of Master of Medical Science at Linköping University. Here he defended his thesis “Uncovering the regulatory machinery required for the transcription of the Wnt target gene AXIN2” after attending Claudio Cantù’s Lab for a period of 6 months in June 2020. Following a post-degree research course in the Cantù Lab, Vittorio started his Ph.D. at the University of Liège where he studies the tumor evolution of a virus-induced type of leukaemia by means of microfluidics single-cell approaches.

Pierfrancesco Pagella

Photo credit John Karlsson Pierfrancesco was born in Alessandria, Italy. He studied Biology at the University of Milano-Bicocca from 2005 to 2011, and then moved to Zurich, Switzerland. During his PhD and his postdoc at the University of Zurich, he focused on the study of teeth, an incredibly powerful model for the study of developmental and evolutionary biology. In this system, he identified and characterized non-canonical functions of several molecules – including the neurotrophin Nerve Growth Factor, the neurite growth inhibitor Nogo-A, and the Wnt/β-catenin transcriptional coactivators Bcl9/9L and Pygo1/2. As Oberassistant/Junior Group Leader at the University of Zurich, he set up microfluidic culture systems to emulate complex organs in vitro, with the aim of modeling and imaging developmental processes. With these microfluidic devices, he could faithfully recapitulate the in vivo tooth innervation patterns.

He exploited these culture systems to compare the neurotrophic properties of dental pulp and bone marrow stromal cells, cell populations currently studied in the context of hard tissue regeneration, as well as cancer cells. In a parallel line of research, he applied single cell RNA sequencing to determine the cellular composition of human teeth, realizing a comprehensive single cell atlas of human teeth.
In April 2021, he joined the lab of Prof. Claudio Cantù at Linkoping University, to gain expertise in the study of chromatin structure, protein / DNA interactions, and how these events affect major developmental and pathological processes.

Jacopo Ulisse

Portrait picture of a man.Jacopo Ulisse. Born and raised in Naples (Italy), Jacopo obtained a bachelor’s degree in 2020 in Health’s Biotechnologies at the University of Naples-Federico II and started an experimental master´s program in Medical Biotechnologies-Advanced Technologies Curriculum at the University of Naples-Federico II. After obtaining a master’s degree in December 2022, Jacopo won a 6-month scholarship grant from the Erasmus + Programme, which he exploited to conduct a traineeship in the Claudio Cantù Lab at Linköping University.

At the moment, Jacopo is participating in an ambitious project aimed at understanding the molecular mechanisms underlying the function of the β-catenin cofactor BCL9, and how it affects cell behaviour and embryonic development. Specifically, Jacopo is becoming specialized in the execution of the proteomics and transcriptomics assays, respectively. Outside work, Jacopo enjoys spending is free time mainly in cooking, watching movies, listening to music and going out for quite long walks.

Gianluca Zambanini

Gianluca Zambanini, member of Claudio Cantù's research group.Gianluca Zambanini, previous member of Claudio Cantù's research group. Photo credit John Karlsson Originally from Riva del Garda (Italy), Gianluca moved to Milan in 2015 to study Biological Science. After 3 years he obtained a bachelor’s degree and started a master´s program at the University of Milano- Bicocca. During the second year of that master´s, Gianluca moved to Linköping to work on a master´s project. During this project, Gianluca focused on the DNA binding detection of β-catenin, a critical component of the WNT signaling pathway. To do so, Gianluca tried to develop a new and improved version of the CUT&RUN protocol first described by the Henikoff Lab in 2017. After the thesis´ defense, Gianluca was awarded a 6-month scholarship by LiU to proceed with his project, aimed at improving the CUT&RUN technology.

Gianluca worked in the Lab as a research assistant using CUT&RUN to study limb development in addition to the differential binding pattern of β-catenin in different tissue and phases of mouse development.

Ongoing Projects

1. Tissue-Specific Wnt-Signalling

A protein called β-catenin orchestrates canonical Wnt target gene expression by recruiting a host of co-factors to Wnt-responsive elements on the DNA, occupied by TCF/LEF transcription factors. Our recent data indicate that the Wnt/β-catenin pathway can affect gene expression in a tissue-specific manner by the recruitment of tissue-specific co-factors. Several of our lines of investigations aim at discovering how cell-type-specific players contribute to the execution of the Wnt-mediated transcription in different cell types: a fundamental question in the field of Developmental Biology.

2. Finding a Therapeutic Window to Treat Colon Cancer

Colorectal cancer (CRC) is prominently caused by uncontrolled activation of the Wnt signalling pathway. However, a complete inhibition of this pathway would have devastating effects on normal tissue homeostasis. In vivo abrogation, in the mouse, of the interaction between β-catenin and BCL9 leads to the loss of metastatic traits without perturbing normal homeostasis. As BCL9 proteins serve as scaffold to a dynamic protein complex that represses and activates Wnt target genes, we are investigating the CRC-specific composition of the Wnt-dependent β-catenin/BCL9 transcriptional complex, as a fundamental first step to identify new players and protein-protein interaction surfaces that might constitute future therapeutic targets. This quest is tightly connected to our fundamental question of embryology: one of our current hypotheses is that one of the regulators of CRC metastasis is TBX3, previously identified by us as a Wnt player in limb development.

3. The Interface Between Transcriptional Regulation and Chromatin Landscape

A central theme of this research line is to understand the relation between the Wnt pathway-mediated transcription and the tissue-specific regulation of chromatin function. We are working hard to respond to the following question: does Wnt signaling impose a specific chromatin structure and function? Or, on the other hand, does the tissue-specific context (i.e. chromatin structure of individual cells) act as fundamental constrain defining how individual cells will respond to Wnt stimulation? This is an ambitious line of investigation that will bring together two fields of research: the study of developmental pathways and molecular epigenetics.

4.The role of Wnt/BCL9 in Congenital Heart Disease (CHD)

We have previously found that the Wnt regulator BCL9 is an important player of heart development. We now hypothesize that genetic variations in the genomic BCL9-regulated regulatory regions might contribute to the onset of congenital heart disorders.

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Claudio Cantù

Wallenberg Centre For Molecular Medicine Linköping (WCMM)

Swedish Developmental Biology Organization (SWEDBO)

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