We are interested in understanding how integrins contribute to almost every step of cancer progression. Current projects focus on finding novel regulators of integrin activity, and endo/exosomal traffic, and on appreciating the mechanisms controlling tumour-stroma cross-talk, including how cancer cells sense key biophysical cues. In addition, we are now using our expertise in these areas, combined with technological advances, to explore the role of integrin-mediated adhesions in maintaining stem cell pluripotency, a concept that is currently underappreciated. This is an exciting new area of research for our lab and one which we hope will lead to exciting discoveries.
Tight control over integrin signalling is paramount for normal cell function and is perturbed in almost every step of cancer progression. Integrin heterodimers can exist in a bent/closed conformation with low affinity for extracellular ligands (‘inactive’) or in an extended/open conformation with a high affinity for ligands (‘active’). Because of this conformational switch, integrins are able to transmit signals bidirectionally across the cell membrane. We have used RNAi screens to identify new proteins implicated in the regulation of integrin activity. We are continuing this work by expanding on our siRNA screens and by developing FRET-based probes to map the spatiotemporal regulation of integrin signalling under different conditions.
Related publications from the lab: Rantala et al., (2011) Nat Cell Biol; Lilja et al., (2017), Nat Cell Biol; Georgiadou et al., (2017) J Cell Biol.
We also focus on identifying integrin-specific regulators that impinge on integrin trafficking pathways to provide a means to selectively target integrins. We have adopted several techniques to study integrin trafficking including the retention using selective hooks (RUSH) system, which can be used to study synchronised receptor recycling under different conditions (e.g. on different extracellular matrix ligands; drug stimulation; loss or gain of function experiments). In addition, we have performed both siRNA screens and comprehensive mass spectrometric analyses of integrin trafficking regulators and our unpublished work has identified key roles for several actin-binding proteins in promoting integrin endocytosis.
Related publications from the lab: Sahgal P et al., (2019), J Cell Sci; Moreno-Layseca et al., (2019) Nat Cell Biol (review); Hamidi H, Ivaska J (2018), Nat Cancer Reviews; Alanko et al., (2015), Nat Cell Biol.
Receptor tyrosine kinase trafficking
There is increasing evidence linking oncogenic signalling of specific RTKs (e.g. MET and EGFR) with their intracellular traffic. We are focusing on HER2 trafficking in the context of HER2-amplified cancers and recently identified a supporting role for the sorting protein SORLA in HER2 recycling back to the plasma membrane. We found that disrupting SORLA-dependent recycling promotes lysosomal dysfunction and sensitises HER2-amplified cancer cells to lysosome-targeting cationic amphiphilic drugs. In our ongoing drug discovery programme, we are further delineating the mechanism of SORLA action in HER2 therapy resistance.
Related publications from the lab: Pietilä et al., (2019), Nat Commun; Barrow-McGee et al., (2016), Nat Commun; Muharram et al., (2014) Dev Cell.
The link between cell states and disease
Embryonic stem cells actively shape their microenvironment and dynamically alter their own state to form organized tissue patterns. Cancer cells bear resemblance to stem cells in their plasticity and ability to adapt to new tissue compositions during metastasis. In contrast, this fundamental property is lost in differentiated cells, which stably maintain their committed state, guided by pre-existing tissue architecture. In collaboration with the Wickström and Mäkitie groups we have launched an exciting new dimension to our research to understand which factors allow cancer cells to bypass established cell-state and tissue barriers, and to explore the possibility to drive cancerous, stem-like states towards normal morphogenesis to limit disease progression.
Mechanobiology of cancer – toolbox
We have a keen interest in untangling the crucial mechanobiological pathways regulating cancer cell behaviour and this has become a central part of many of our investigations. To this end, we are expanding our toolbox, both through vital collaborations and through method development, to improve the biological relevance of our experiments (i.e. application of force, tuning force dynamics and the analysis of the mechanoresponse). Examples of our method development include: superresolution traction force microscopy, stiffness gradient hydrogels and micropatterning.
Related publications from the lab: Stubb et al., (2020), Nano Letters; Nuria Barber-Perez (2019), BioRxiv
Integrins in filopodia adhesions
Filopodia are important finger-like cellular protrusions that probe and then relay microenvironmental details back to the cell during normal processes such as development and wound healing. However, filopodia and filopodia-like structures are also implicated in cancer progression. Since filopodia contain integrin receptors and integrins are the primary contact between the extracellular space and the cell’s cytoskeleton, we are aiming to get a better understanding of how these receptors are regulated in filopodia both in terms of activation and transport to filopodia tips. This work is in collaboration with the Jacquemet lab.
Related publications from the lab: Jacquemet et al., (2019), Curr Biol; Jacquemet et al., (2017), J Cell Biol; Jacquemet et al., (2016), Nat Commun.
hiPSC adhesions, cytoskeleton and pluripotency
Pluripotent stem cells can differentiate into all cell types of the human body and therefore hold great promise for regenerative medicine. Our data suggest that focal adhesion architecture and cytoskeletal contractility are important gatekeepers of human pluripotent stem cell (hPSC) differentiation. Our superresolution microscopy analyses (interferometric photoactivated localization microscopy; iPALM) also demonstrate the unique nanoscale organization of hPSC focal adhesions, the cell’s mechanotransducing units, and their actin linkage. Our ongoing work aims to define how integrin-mediated adhesions control cell states and impact on pluripotency.
Related publications from the lab: Stubb et al., (2019), Nat Commun; Närvä et al., (2017), Stem Cell Reports.
Thanks to Our Funders
Our projects have received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme, the Academy of Finland, the Cancer Society of Finland and the Sigrid Juselius Foundation.
Johanna Ivaska – The Boss
Brief background (Link to CV): Johanna Ivaska is a Professor of Molecular Cell Biology at the University of Turku in Finland. After obtaining her PhD at the University of Turku and following a post-doc in the laboratory of Peter Parker in CR-UK London Research Institute, she started her own group at the VTT Technical Research Centre of Finland. In 2013, she joined the University of Turku Bioscience Centre where she currently leads the “Cell Adhesion and Cancer” group. In 2015, she was awarded the highly prestigious national research professorship from the Academy of Finland. Her primary research relates to the biological role of integrins in cancer progression and, in particular, integrin-mediated cell adhesion and migration, cell-matrix interactions and mechanosensing, and the molecular mechanisms governing endosomal traffic of integrins and growth factor receptors in cancer. She is recognized as a leader in her field with numerous commissions of trusts including editorial duties in leading scientific journals, organization of international conferences and as a member of scientific advisory boards. She is regularly invited to speak globally at internationally recognised conferences (Gordon Conferences, EMBO meetings, ASCB) and institutes (MIT, Mount Sinai New York, Cancer Research UK, Institute Curie, Institute Pasteur, UCL, King’s College, University of Cambridge, IFOM Milan, IBEC Barcelona, MPI Cologne and University of Geneva). In addition to reviewing for the European Research Council, Johanna has also been a recipient of major research grants including an ERC StG, an ERC CoG and 3 x ERC PoC grants. She has also been a member of the LS3 CoG panel. Johanna’s contributions to research have been recognised through elected memberships to EMBO and to the Finnish Academy of Science and Letters. In 2011, she was awarded the Anders Jahre Prize and, in 2017, the Orion pharma research prize and the A.I. Virtanen medal for internationally recognized excellence in biomedical research.
Hussein Al Akhrass – Postdoc
My postdoc focuses on understanding the effect of endosomal sorting events on receptor tyrosine kinase signaling in cancer. I use biochemical assays and imaging approaches to study intracellular transport of membrane receptors by sortilin-related receptor – a well reported protein for its role in Alzheimer’s and metabolic diseases. I spend a significant amount of time exploring new cancer-related databases, among which cBioPortal is my favorite. Working in synergy with my colleagues is a value that makes research more meaningful!
James Conway – Postdoc
I am a postdoctoral research fellow working on image-based screening approaches and cancer invasion. During my undergraduate studies at the University of Adelaide in Australia, I majored in Chemistry and Biochemistry, conducting an honours degree in the lab of Prof. Greg Goodall working on the development of miRNAs as therapeutics in neuroblastoma. Moving to the lab of Prof. Paul Timpson in Sydney, my PhD focused on the development of a intravital imaging approach to track therapeutic responses in areas of low oxygen in live mouse xenografts. My work is now centred around the development of new fluorescent FRET reporters for RNAi screening of the phosphatases that regulate integrin activity.
Gautier Follain – Postdoc
Coming from France, I’m a joint Postdoctoral researcher working in J. Ivaska and G. Jacquement laboratories. I obtained my Bachelors, in Cell Biology and Physiology, and, Masters, in Developmental Biology and Stem Cells, from the University of Strabourg. I then joined the lab of J. Goetz to study the impact of hemodynamic forces on the metastatic cascade. Now, I am working on the role of cell protrusions during PDAC intravascular arrest, adhesion and extravasation.
A good working day starts with cell culture, keeps on going with imaging of zebrafish embryos and finishes with a beer.
Hellyeh Hamidi – Research Support Coordinator
Originally from the UK, I did my PhD in the laboratory of Prof Martin Humphries in the Wellcome Trust Cetre for Cell-Matrix Research, University of Manchester. I then did a postdoc with Prof Rachel Lennon, before moving to Finland for my current position. I try my best to take care of the group, to manage visibility of the lab, help in scientific writing and to be the communication bridge between academics and admin. It is a busy job but I love it!
Aleksi Isomursu – PhD Student
Originally from the north of Finland, I acquired my Bachelor’s and Master’s degrees in Cell and Molecular Biology from the University of Jyväskylä, while working in the laboratories of J. Bamford and T. Kuopio. My undergrad studies and time spent abroad as an exchange student both shaped my interest in human malignancies and cell-matrix interactions; consequently, I sought to join the Ivaska lab as a PhD student. My current projects revolve around cancer cell mechanotransduction, inclucing mechanosensitive transcription factors and mechanically directed cell migration. Outside work, I like to relax by exercising and catching up with friends.
Niklas Jäntti – PhD Student
I did my Master’s thesis work in the Ivaska Lab investigating the role of the sorting receptor SORLA in the endosomal trafficking of the growth factor receptor HER2. I’ve been a PhD student in the lab since September 2019, studying the interplay between cancer cell adhesion, cytoskeletal dynamics and membrane trafficking and exploring the regulatory network that coordinates these processes, with the goal of identifying new mechanisms to prevent metastasis. What I enjoy most about working here is the great people, the dynamic atmosphere and the possibility to do some world-class microscopy. During my free time I like to do sports such as bouldering or swimming and I also sing in a choir and play the guitar.
Jasmin Kaivola – PhD Student
I am a phD student at the Ivaska lab and I’m working on integrin regulators and mechanosensing in cancer. I previously studied biochemistry at University of Turku (BSc and MSc). During my studies I worked as a research assistant on hormonal regulation of breast cancer (Lab run by Prof. Pirkko Härkönen).
David Kühl – Master‘s Student
To finish my master’s degree at the University of Applied Sciences Bremen in Germany, I am currently working on my master’s thesis in Johanna Ivaska’s laboratory. Coming from a microbiological background through my bachelor’s degree, I first entered the field of biology through my work on plant genetics, but during my semesters abroad I focused my interests towards cell biology and cancer research. Currently I am working on the phosphorylation of integrins. In addition to research work I like to explore the unspoiled nature of Finland.
Petra Laasola – Biomedical Laboratory Scientist
I previosuly worked at VTT Technical Research Centre of Finland as part of the biochip-team, where I helped to test, develop and prepare Cell Spot Microarrays (CSMA). I then joined the Ivaska lab several years ago where I help in the day-to-day running of the lab. I have experience in many other molecular biology techniques including immunoprecipitation, PLA, tissue staining, immunofluorescence and FACS analysis.
Martina Lerche – PhD Student
I am a PhD student with a crush on mechanosensing. I grew up in the Finnish archipelago and obtained my Master’s in Biosciences from Åbo Akademi University (master’s project done in the laboratory of Professor Cecilia Sahlgren). My research focus is integrin activity regulation and trafficking, and how these processes are affected by the properties of the ECM. To better understand these questions I have set up both the RUSH-system and traction force microscopy in our lab. I do most of my experiments on micropatterns or hydrogels as plastic seems a bit passé. A perfect day is made up from a long run, strong coffee, great colleagues and some intriguing microscopy.
Johanna Lilja – PhD Student
I am a final year PhD student. During my PhD, I have been working on the role of integrin inactivators in cancer cell motility and the tumour microenvironment. Currently, I’m studying lethal vulnerabilities in KRAS-mutant cancers. A good working day starts with a cup of coffee and continues with a fun day at lab with great collegues.
Valentijn van der Linden – Intern
I’m working on my bachelor of Applied Sciences in the Netherlands. I’m doing my internship at the Ivaska Lab where I’m investigating intracellular trafficking of RTK’s in breast cancer. My hobbies include playing the cello and piano plus a lot of sports, I love to swim and run.
Mitro Miihkinen – PhD Student
Filopodia are important cellular protrusions implicated in development and disease. My PhD project aims to dissect the mechanisms regulating filopodia adhesions with a focus on integrins and MYO10.
Paulina Moreno-Layseca – Postdoc
I’m an Academy of Finland postdoctoral researcher originally from Mexico. I did my PhD at the University of Manchester, UK with Prof C. Streuli, and a postdoc in Hamburg, Germany, working with Dr S. Veltel before joining the Ivaska lab. I’m interested in integrin traffic controlled by Rab21, the actin cytoskeleton and their interplay during cancer progression. The key to a great day is listening to cheerful music, tea and biscuits, lots of microscopy, plenty of scientific debates, efficiency and good results!
Nicolas Pasquier – Intern, soon to be PhD student
Originally from France, I did my Master of Engineering at the ESPCI Paris. I am currently doing an internship where I aim at building a MCF10A-based 3D model to study the effect of Rab21 and Swiprosin1 on breast acini formation and the integrin trafficking within them. As from September 2020, I will start a joint PhD between the Ivaska Lab and the Jaulin Lab at the Institut Gustave Roussy (Villejuif, France) where I will study the role of oncogenic and mechanotransduction alterations in the focal-adhesion pathway on the colorectal metastasis polarity. A perfect day starts with a cup of coffee, continues with great colleagues and lots of microscopy, an insane amount of music (listening and playing), a good run, and ends with a nice beer with friends!
Siiri Salomaa – PhD Student
I am a final year PhD candidate studying regulation of the actin cytoskeleton and cell adhesion in different cell types. In my Bachelor’s and Master’s, I have worked with vascular pathologies in the brain. My days get a good start with a proper breakfast and good coffee, and interesting and inspiring discussions with my colleagues keep me going. In my free time I like doing various sports and photography, and I also have a super happy and fluffy little dog.
Jenni Siivonen – Biomedical Laboratory Scientist
I have been an Ivaska lab member for several years and I help in the day-to-day running of the lab. I have experience in many techniques including but not limited to recombinant protein production, RNA and DNA isolation, imunofluorescence and western blotting.
Maria Taskinen – PhD Student
I’m a PhD student working mainly on cancer and stem cells, MASTL, cell adhesion and actin cytoskeleton. I obtained my Bachelors and Masters in Biochemistry at the University of Turku. A good day at work consists of cell imaging, coffee and great work mates.
- Aki Stubb (thesis defended 2019) – soon to be postdoc, Ewa Paluch lab, University of Cambridge, UK
- Pranshu Sahgal (thesis defended 2018) – now postdoc in the Dana-Farber Cancer Institute, US
- Jonna Alanko (thesis defended 2016) – now postdoc in the Michael Sixt lab, IST, Austria
- Riina Kaukonen (thesis defended 2016) – now postdoc in Turku Bioscience Centre
- Nicola De Franceschi (thesis defended 2016) – next step: postdoc in Institute Curie, FR
- Reetta Virtakoivu (thesis defended 2015) – now postdoc in Institute of Biomedicine, FI
- Antti Arjonen (thesis defended 2013)
- Gunilla Högnäs (thesis defended 2013) – now postdoc University of Tampere, FI
- Anja Mai (thesis defended 2011)
- Juha Rantala (thesis defended 2011) – now CEO at Misvik Biology and Principal Investigator at the University of Sheffield, UK
- Jonna Nevo (thesis defended 2011) – now MD, Oncologist
- Karolina Vuoriluoto (thesis defended 2010) – now Drug Safety Specialist, Orion Corporation
- Saara Tuomi (thesis defended 2010) – Next step: Postdoc at the Danish Cancer Society
- Teijo Pellinen (thesis defended 2009) – now Senior Researcher at Institute for Molecular Medicine Finland (FIMM), Helsinki, Finland
- Elina Mattila (thesis defended 2009) – now Senior Scientist at Orion Pharma, Finland
- Max Grönloh
- Niklas Jäntti
- Nuria Barber Perez
- Rafael Saup
- Maria Rafaeva
- Jaroslav Icha – October 2019; next step: Application Specialist, Promega, Prague, Czechia
- Emilia Peuhu – August 2019; next step: Principal Investigator, Peuhu lab, Institute of Biomedicine, University of Turku, Finland!
- Guillaume Jacquemet – August 2019; next step: Principal Investigator, Cell Migration Lab, Åbo Akademi University, Finland!
- Ilkka Paatero – August 2019; next step: Head of Zebrafish Facility, Turku Bioscience Centre, University of Turku
- Camilo Guzmán – October 2018; next step: Facility manager (Nanophotonics) at the International Iberian Nanotechnology Laboratory, Portugal
- Maria Georgiadou – August 2018; next step: Senior Researcher at Orion Pharma, Finland
- Mika Pietilä – until 2017; next step: Medical Advisor, Astra Zeneca, Espoo, Finland
- Anja Mai – until 2016; next step: Researcher at BerGenBio, Bergen, Norway
- Antti Arjonen – until 2015; next step: Senior researcher at Misvik Biology Ltd, Turku, Finland
- Ghaffar Muharram – until 2013; next step: Scientist at University of Lille, Lille, France
- Jeroen Pouwels – until 2013; next step: group leader at Turku Bioscience Centre, Turku, Finland
- Stefan Veltel – next step: lecturer at University of Applied Sciences, Bremen, Germany
We are located in Turku Bioscience at the University of Turku.
University of Turku
Turku Biosience Centre
Thanks to the FinELib consortium (Finnish universities, research institutions and public libraries) we have been able to make our most recent publication in Nano Letters open access! “Fluctuation-Based Super-Resolution Traction Force Microscopy” What a great initiative! We hope you enjoy reading the paper!
Thanks to everyone who applied to our two postdoc positions! We had a lot of applications and will get back to you shortly! Please bear with us.