Welcome to our lab!

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. We are also investigating signal integration and synergy between integrin regulatory pathways and oncogenic signalling axes in cancer.

20210208_120251
One of those big days for Ivaska lab !
Capture d’écran 2021-11-17 à 17.35.57
Latest paper !
Capture d’écran 2021-11-17 à 17.47.29
Latest funding !
hiPSC
Confocal image of human induced pluripotent stem cell (hiPSC) colony stained with SiR-Actin and DAPI.
Courtesy of Maria Taskinen
Slide
Pancreatic cancer cells migrating on a stiffness gradient gel
Courtesy of Mathilde Mathieu
PlayPlay
FRET imaging
Quantitative imaging. FLIM-FRET images of MDA-MB-231. Stable expression of LynIB1B treated with different phosphatase inhibitors. Sc. bars, 20 μm.
Courtesy of James Conway
Slide
PlayPlay
Mucin-secreting peritoneal carcinosis CRC organoid in collagen
Courtesy of Nicolas Pasquier
Slide
Confocal image of telomerase-immortalised human fibroblasts, stained with DAPI, phalloidin and anti-paxillin
Courtesy of Aleksi Isomursu
Slide
PlayPlay
MDA-MB-231s embedded in a mix of Matrigel and collagen I
Courtesy of Aleksi Isomursu
Slide
Tumor cell injected in the brain ventricles cavity of
a 48h zebrafish embryo
Courtesy of Gautier Follain
previous arrow
next arrow

Our Research

Microenvironmental containment of tumours

We have previously uncovered key differences between normal and cancer-associated stroma, whereby the mechanical and architectural features of normal stroma inhibit tumour growth and may epigenetically reprogram aggressive breast cancer cells towards a more benign phenotype. Recently, we turned our attention to other putative crosstalk mechanisms between cancer cells and the microenvironment. We discovered that normal stromal components can also inhbit cancer cell invasion and migration towards the vasculature. We are now investigating the mechanisms for this in a newly funded Worldwide Cancer Research project.

Related publications from the lab: Kaukonen et al., 2016, Normal stroma suppresses cancer cell proliferation via mechanosensitive regulation of JMJD1a-mediated transcription, Nature communications

Cell adhesion and cancer

Tissue homeostasis is dependent on the spatially controlled localization of specific cell types and the correct composition of the extracellular stroma. Integrin mediated adhesions, in conjunction with the actin cytoskeleton, regulate cell faith and identity and allow cells to migrate and invade the surrounding extra-cellular matrix (ECM). Tight control over integrin mediated adhesion and signalling is paramount for normal cell function and is perturbed in almost every step of cancer progression. Our long-standing interest is in uncovering cancer relevant integrin-associated proteins and signalling networks. We have used RNAi screens to identify new proteins implicated in the regulation of integrin activity, integrin traffic, cell migration and metastasis. We are continuing this work by 1) investigating in mechanistic detail adhesion regulating protein networks using proximal-biotinylation, by 2) developing FRET-based probes to map the spatiotemporal regulation of integrin signalling under different conditions, by 3) screening for cell response to varying ECM compositions.

Related publications from the lab: Salomaa et al., (2021), Curr Biol ; Miihkinen et al., (2021) Cell Reports ; Taskinen et al., (2020), JCB ; Rantala et al., (2011); Nat Cell Biol ; Lilja et al., (2017), Nat Cell Biol; Georgiadou et al., (2017) J Cell Biol

Integrin trafficking

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 most recent work has identified key roles for actin-binding protein swiprosin-1 in directing integrin endocytosis to the CG-pathway thus promoting integrin endocytosis and cell migration. Accordingly, high levels of swiprosin-1 correlates with a significant increase in breast cancer metastasis in large cohort of triple-negative breast cancer.

Related publications from the lab: Moreno-Layseca et al., (2021) Nat Cell Biol; 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: Al Akhrass et al., (2021), Mol. Onco.; Al Akhrass et al., (2021), Oncogene; Pietilä et al., (2019), Nat Commun; Barrow-McGee et al., (2016), Nat Commun; Muharram et al., (2014) Dev Cell.

Biophysical regulation of cancer cells

The cells of a multicellular organism will encounter a wide range of biophysical cues, ranging from tensile and compressive forces to the architecture and visco-elasticity of the surrounding extracellular matrix. Such mechanobiological interactions can directly impact cell signaling and function, including the survival, growth and motility of individual cancer cells. Despite this, the nature of many biomechanical signals and how they are interpreted by the cells remain poorly understood. We work on that! For example, healthy extracellular matrix can have an anti-tumorigenic function through epigenetic regulation, as we published few years ago (Kaukonen et al. 2016). On the same line, substrate mechanics can also influence cell migration directly, as many cell types are known to sense and move toward stiffer matrix; the process called durotaxis. Similar gradients are found in tumors, and we have now uncovered a previously unappreciated capacity of cancer cells to migrate against stiffness gradients, toward softer environments, to an optimal situation. Finally, while many studies so far have focused on the elastic properties of the matrix, some tissue types are also naturally exposed to more dynamic forces. We are studying how such mechanical perturbations can influence tumorigenesis and, conversely, how tissue mechanics may be influenced by tumor progression.

Related publications from the lab: Isomursu et al., (2020), BioRxiv; Kaukonen et al. (2016), Nat. comm.

Imaging Metastasis

Circulating tumor cells are able the stop in small capillaries, engage stable adhesions with endothelial cells and transmigrate through the vessel walls. These are key steps of the metastatic cascade that are still poorly understood. Nonetheless, they directly precede the formation of life-threatening metastases. We develop microfluidic models and use in vivo models to study the fundamental aspect of these steps in relevant biomechanical conditions. Of particular interest, we study the role of filopodia-like protrusions and the adhesion receptors decorating them, as well as the key role of endothelial cells as a barrier against metastatic spreading. The project is running in close collaboration with the Jacquemet lab.
This project is supported by two recent and important funding source : JAES foundation until 2025 and the formation of the new Center of Excellence from Academy of Finland – BarrierForce until 2029 !

Related publications from the lab: Jacquemet et al., (2019), Curr Biol; Jacquemet et al., (2017), J Cell Biol; Jacquemet et al., (2016), Nat Commun.

Tools for Mechanobiology

Due to our continued interest in untangling the mechanobiological pathways that regulate cancer cell behaviour, we are always expanding our toolbox for interrogating and controlling the different biophysical features of cells and their environment. Through vital collaborations and in-house method development, we seek to improve the biological relevance of our experiments. Some examples of new methodology include super-resolution traction force microscopy, used for measuring the contractile forces exerted by individual cells on their surroundings; stiffness gradient hydrogels, for studying how substrate mechanics can direct cell-matrix interactions and migration; new micropatterning applications, for controlling cancer cell morphology and dynamic interactions with different extracellular matrix components; and microfluidic shear stress modeling, for studying cancer cell intravascular adhesion.

Related publications from the lab: Stubb et al., (2020), Nano Letters; Nuria Barber-Perez (2020), JCS.

Translational cancer drug discovery

One of the key focus areas of the laboratory is to take fundamental research discoveries in cancer cell biology towards translation. We have currently two ongoing drug discovery projects linked to ERC Proof-of-concept funding:

RASaTAC – Regulating RAS Activity to Target RAS-Driven Cancers (ERC funding 2020-2022)

RAS are a family of genes whose mutations are implicated in a variety of different cancers. Despite their ubiquitous oncogenic activity, no effective anti-RAS therapies exist today. Prior work by us had shown that a class of scaffold proteins bind to mutated forms of RAS proteins. In cancer this interaction moderates RAS signaling and triggers cytotoxic signalling and leads to cell death. We are currently working in collaboration with a biotech start-up company to develop drugs that interfere with these scaffold proteins as an innovative approach to target RAS-driven cancers. The results will offer a novel cancer treatment option to patients that do not respond to current standards of care.

Related publications from the lab: Lilja et al., (2022), BioRxiv; Lilja et al., (2017), Nat. Cell Biol.

SaveHER – The inhibition of sorting proteins as a therapeutic avenue in HER2 positive breast cancer (ERC funding 2018-2019)

Research from our laboratory has uncovered novel therapeutic targets in cancer. We have focused on HER2 trafficking in the context of HER2-amplified cancers and identified a supporting role for the sorting protein SORLA in the recycling and concogenic signalling of HER2 and HER3 receptor tyrosine kinases back to the plasma membrane. We have shown that disrupting SORLA-dependent recycling compromises the oncogenic fitness of HER-driven breast and bladder cancer in vitro and in vivo. Furthermore, SORLA-depletion re-sensitises anti-HER2 therapy resistant breast cancer cells to therapy and limits expansion of brain metastasis. We have recently generated a function-blocking antibody against SORLA and demonstrated efficacy in xenografts and primary patient derived explant cultures. In our ongoing drug discovery programme, we are further delineating the mechanism of SORLA action in HER2 therapy resistance and developing anti-SORLA therapy.

Related publications from the lab: Al Akhrass et al., (2021), J. Mol. Oncol.; Al Akhrass et al., (2021), Oncogene; Pietilä et al., (2019), Nat. Commun.

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.

This area of our research is supported by Academy of Finland. Funded research program: Molecular Regulatory Networks of Life (R’Life) 2020–2023. Nucleomechanical regulation of cell states – from pluripotency to cancer (NucleoMech)

Our research is only possible because of our generous 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 Finnish Cancer Foundation and the Sigrid Juselius Foundation.

Lab Members

Johanna Ivaska – The Boss

Brief background (Link to CV): Johanna is a K Albin Johansson Professor at the University of Turku. She started her own group at the VTT Technical Research Centre of Finland in 2003. In 2013, she joined the University of Turku Bioscience Centre where she currently leads the “Cell Adhesion and Cancer” group.

Contact: johanna.ivaska[at]utu.fi / hellyeh.hamidi[at]utu.fi

Megan Chastney – Postdoc

I am a postdoctoral researcher in the Ivaska lab, interested in the role of mechanical forces in cancer progression. I obtained my Bachelors in Biochemistry at the University of Manchester, UK, where I then obtained my PhD in the laboratory of Prof Martin Humphries at the Wellcome Trust Centre for Cell-Matrix Research, using proximity biotinylation to investigate mechanisms of mechanotransduction in pancreatic cancer. My work now focuses on how cells respond to mechanical stimuli via integrin adhesion complexes and the cytoskeleton during laryngeal cancer progression.

Contact: megan.chastney[at]utu.fi

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 approaches 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. 

Contact: james.conway[at]utu.fi

Michal Dibus- Postdoc

Originally from Slovakia, I completed my Ph.D. in the Laboratory of Cancer Cell Invasion at Charles University in Prague, Czech Republic, under the supervision of Prof. Jan Brábek and A/Prof. Daniel Rösel, where I studied the role of kinase signalling in regulation of small Rho GTPases and cancer progression. Currently, I am a postdoctoral researcher at Ivaska lab interested in mechanistic and functional aspects of the negative regulation of integrin activity. Outside the lab, I love black and white film photography and growing botanical orchid species.

Contact: michal.dibus[at]utu.fi

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.

Contact: gautier.follain[at]utu.fi

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!

Contact: hellyeh.hamidi[at]utu.fi

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.

Contact: aleksi.isomursu[at]utu.fi

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.

Contact: niklas.z.jantti[at]utu.fi

Omkar Joshi – PhD Student

I completed my BS-MS dual degree from the Indian Institute of Science Education and Research (IISER), Pune, India while working in the lab of Dr. Nagaraj Balasubramanian. I joined the Ivaska Lab in May 2022 for my PhD. My work focuses on the protein STOML2 and its role(s) and regulation in adhesion-mediated cellular behaviors in normal versus cancer cells. Beyond science, I love playing badminton (or any other racquet sport). So ping me, and we’ll play 🙂

Contact: omkar.joshi[at]utu.fi

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). 

Contact: jasmin.e.kaivola[at]utu.fi

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.

Contact: petra.laasola[at]utu.fi

Mathilde Mathieu – Postdoc

I am a French postdoctoral researcher. I did my master at the University Paris IV and the ENS Paris Saclay. For my PhD, I worked in Clotilde Théry’s lab at the Institut Curie in Paris, where I studied the trafficking of tetraspanins towards their secretion into different types of extracellular vesicles. My postdoc project focuses on how cancer cells migrate from the stiff tumor environment to softer environments. Outside the lab I like to go to rock concerts, visit art museums and travel to explore the world around me.

Contact: mathilde.mathieu[at]utu.fi

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!​

Contact: paulina.morenolayseca[at]utu.fi

Veli-Matti Leppänen – Research Fellow

I am a senior researcher with special interest in protein structural biology.

Contact: veli-matti.leppanen[at]utu.fi

Nicolas Pasquier – Joint 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!

Contact: nicolas.pasquier[at]utu.fi

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.

Contact: jenni.siivonen[at]utu.fi

Our Alumni

PhD Students

  • Maria Taskinen (thesis defended 2022) – next step: Paul Workman’s lab, ICR, London, UK
  • Mitro Miihkinen (thesis defended 2021) – next step : studying statistics at University of Turku, FI.
  • Martina Lerche (thesis defended 2021) – next step : postdoc, Clare Waterman’s lab, NIH, US
  • Siiri Salomaa (thesis defended 2020) – next step : postdoc, Kevin Chalut’s lab, University of Cambridge, UK
  • Johanna Lilja (thesis defended 2020) – next steps : postdoc, Johanna Joyce’s lab, University of Lausanne, CH
  • Aki Stubb (thesis defended 2019) – next steps : postdoc, Ewa Paluch’s lab, University of Cambridge, UK
  • Pranshu Sahgal (thesis defended 2018) – next step : postdoc in the Dana-Farber Cancer Institute, US
  • Jonna Alanko (thesis defended 2016) – next step : postdoc in the Michael Sixt lab, IST, Austria
  • Riina Kaukonen (thesis defended 2016) – next step : postdoc in Turku Bioscience Centre
  • Nicola De Franceschi (thesis defended 2016) – next step: postdoc in Institute Curie, FR
  • Reetta Virtakoivu (thesis defended 2015) – next step : postdoc in Institute of Biomedicine, FI
  • Antti Arjonen (thesis defended 2013)
  • Gunilla Högnäs (thesis defended 2013) – next step : postdoc University of Tampere, FI
  • Anja Mai (thesis defended 2011)
  • Juha Rantala (thesis defended 2011) – next step : CEO at Misvik Biology and Principal Investigator at the University of Sheffield, UK
  • Jonna Nevo (thesis defended 2011) – next step : MD, Oncologist
  • Karolina Vuoriluoto (thesis defended 2010) – next step : 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

Master‘s Students

  • Max Grönloh
  • Niklas Jäntti
  • Nuria Barber Perez
  • Rafael Saup
  • Maria Rafaeva
  • David Kühl
  • Taru Varila
  • Sonja Vahlman
  • Paula Rasila

Postdocs

  • Hussein Al Akhrass – July 2021; next step: R & D Manager, Boehringer and Ingelheim, Vienna, Austria
  • Elisa Närvä – April 2021; next step: Principal Investigator, Pluripotency & Cancer Laboratory, Institute of Biomedicine, University of Turku, Finland!
  • 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

Contact

We are located in Turku Bioscience at the University of Turku.

Our address

University of Turku
Turku Biosience Centre
Tykistökatu 6
FI-20520

Opportunities

If you are interested in joining the Ivaska lab as a postdoctoral fellow, please contact Professor Ivaska: johanna.ivaska@utu.fi

Blog

Posted on

Successful establishment of a new Center of Excellence from Academy of Finland !

Ivaska Lab looking forward to exciting 8 years with the BarrierForce Center of Excellence. The CoE, directed by Johanna Ivaska, was selected as one of the new Aacdemy of Finland Centers of Excellence. The Academy of Finland selected eleven Centres of Excellence (CoE) for the period 2022‒2029.The call for Finnish Centres of Excellence attracted a …

Continue reading “Successful establishment of a new Center of Excellence from Academy of Finland !”