Talents

Vici grant for Sander Leeuwenburgh

Regeneration of diseased bone by biomaterials built from nanoparticles.
Awarded Radboudumc: 1,500 kEuro

Sander Leeuwenburgh received an 1,500 kEuro Vici research grant from the Netherlands Organisation for Scientific Research (NWO). He will use the money to conduct research over the next five years and build up his own research group. The Vici grant is one of the largest personal scientific grants of the Netherlands. In 2020, the NWO awarded 32 Vici grants in total (seven Vici grants for Radboud University medical center and University). 

Sander Leeuwenburgh is professor Regenerative Biomaterials. His research group is developing injectable and self-healing biomaterials which stimulate the regenerative capacity of the human body. 

Currently available biomaterials are not able to heal defects in diseased bone effectively. In this project novel self-porous and healing biomaterials will be self-assembled from nanoparticles to release antibacterial and anticancer drugs directly into cells. These new properties will accelerate bone regeneration and combat bone diseases effectively.

Veni grants for Jorge Dominguez Andres and Pascal Miesen

Time for a boost: metabolic potentiation of vaccines. Jorge Dominguez Andres, Internal Medicine.
Awarded Radboudumc: 250 kEuro.

Traditional vaccines have two components, antigen and adjuvant, which often provide only partial effectiveness against specific diseases. The addition of a third component, a metabolic amplifier, represents the next step to develop a new generation of vaccines that can be used against multiple diseases.

RNA helicases - novel factors for virus transmission by mosquitoes. Pascal Miesen, Medical Microbiology.
Awarded Radboudumc: 250 kEuro.

Aedes aegypti mosquitoes transmit important human viruses such as dengue and Zika virus. The efficiency of transmission depends on how well these viruses replicate in the mosquito. The researchers investigate the role of a gene from the family of so-called RNA helicases in determining virus replication and transmission by mosquitoes.

Marie Curie Global Fellowship for Maria Ibars Serra

OMG - OIT3: A novel Magnesiotropic Gene in Kidney. Maria Ibars Serra, Renal disorders. 
Total grant: 271 kEuro. Awarded Radboudumc: 94 kEuro.

Maria Ibars Serra, postdoc at the Department of Physiology, theme Renal disorders, is awarded with a Marie-Curie Global Fellowship. The next three years she will focus on unraveling the role of a mysterious gene involved in magnesium balance in the body. This research will provide new functional insights on renal magnesium handling and contribute to the discovery of potential therapeutic targets and biomarkers of electrolyte-related kidney disease. With this personal grant, Maria will work together with Joost Hoenderop, Department of Physiology and Ron Korstanje at The Jackson Laboratory, Bar Harbor, USA. 

The Marie Sklodowska-Curie fellowships are Europe's most prestigious awards.They support researchers at all stages of their careers, regardless of age and nationality. The MSCA also support cooperation between industry and academia and innovative training to enhance employability and career development.

Beautiful publications by Peter Friedl and coworkers

2020 has been an awesome scientific year for Peter Friedl. He published as senior author several outstanding studies in internationally leading journals. We proudly present here three examples to illustrate his success.

Ilina O, Gritsenko PG, Syga S, Lippoldt J, La Porta CAM, Chepizhko O, Grosser S, Vullings M, Bakker GJ, Starruß J, Bult P, Zapperi S, Käs JA, Deutsch A,Friedl P. Cell-cell adhesion and 3D matrix confinement determine jamming transitions in breast cancer invasion. Nat Cell Biol. 22:1103-1115, 2020. PMID: 32839548

Plasticity of cancer invasion and metastasis depends on the ability of cancer cells to switch between collective and single-cell dissemination, controlled by cadherin-mediated cell-cell junctions. In clinical samples, E-cadherin-expressing and -deficient tumours both invade collectively and metastasize equally, implicating additional mechanisms controlling cell-cell cooperation and individualization. Here, using spatially defined organotypic culture, intravital microscopy of mammary tumours in mice and in silico modelling, we identify cell density regulation by three-dimensional tissue boundaries to physically control collective movement irrespective of the composition and stability of cell-cell junctions. Deregulation of adherens junctions by downregulation of E-cadherin and p120-catenin resulted in a transition from coordinated to uncoordinated collective movement along extracellular boundaries, whereas single-cell escape depended on locally free tissue space. These results indicate that cadherins and extracellular matrix confinement cooperate to determine unjamming transitions and stepwise epithelial fluidization towards, ultimately, cell individualization.

Khalil AA, Ilina O, Vasaturo A, Venhuizen JH, Vullings M, Venhuizen V, Bilos A, Figdor CG, Span PN, Friedl P. Collective invasion induced by an autocrine purinergic loop through connexin-43 hemichannels. J Cell Biol. 219:e201911120, 2020. PMID: 32777015

Progression of epithelial cancers predominantly proceeds by collective invasion of cell groups with coordinated cell-cell junctions and multicellular cytoskeletal activity. Collectively invading breast cancer cells express the gap junction protein connexin-43 (Cx43), yet whether Cx43 regulates collective invasion remains unclear. We here show that Cx43 mediates gap-junctional coupling between collectively invading breast cancer cells and, via hemichannels, adenosine nucleotide/nucleoside release into the extracellular space. Using molecular interference and rescue strategies, we identify that Cx43 hemichannel function, but not intercellular communication, induces leader cell activity and collective migration through the engagement of the adenosine receptor 1 (ADORA1) and AKT signaling. Accordingly, pharmacological inhibition of ADORA1 or AKT signaling caused leader cell collapse and halted collective invasion. ADORA1 inhibition further reduced local invasion of orthotopic mammary tumors in vivo, and joint up-regulation of Cx43 and ADORA1 in breast cancer patients correlated with decreased relapse-free survival. This identifies autocrine purinergic signaling, through Cx43 hemichannels, as a critical pathway in leader cell function and collective invasion.

Gritsenko PG, Atlasy N, Dieteren CEJ, Navis AC, Venhuizen JH, Veelken C Schubert D, Acker-Palmer A, Westerman BA, Wurdinger T, Leenders W, Wesseling P,Stunnenberg HG, Friedl P. p120-catenin-dependent collective brain infiltration by glioma cell networks. Nat Cell Biol. 22:97-107, 2020. PMID: 31907411

Diffuse brain infiltration by glioma cells causes detrimental disease progression, but its multicellular coordination is poorly understood. We show here that glioma cells infiltrate the brain collectively as multicellular networks. Contacts between moving glioma cells are adaptive epithelial-like or filamentous junctions stabilized by N-cadherin, β-catenin and p120-catenin, which undergo kinetic turnover, transmit intercellular calcium transients and mediate directional persistence. Downregulation of p120-catenin compromises cell-cell interaction and communication, disrupts collective networks, and both the cadherin and RhoA binding domains of p120-catenin are required for network formation and migration. Deregulating p120-catenin further prevents diffuse glioma cell infiltration of the mouse brain with marginalized microlesions as the outcome. Transcriptomics analysis has identified p120-catenin as an upstream regulator of neurogenesis and cell cycle pathways and a predictor of poor clinical outcome in glioma patients. Collective glioma networks infiltrating the brain thus depend on adherens junctions dynamics, the targeting of which may offer an unanticipated strategy to halt glioma progression.

Niels Stensen Fellowship for Jorieke Weiden

Niels Stensen Fellowship to fund a postdoc at École polytechnique fédérale de Lausanne (EPFL) in Lausanne, Switzerland. Jorieke Weiden, Cancer development and immune defence.
Awarded Radboudumc: 58 kEuro.

Jorieke Weiden, theme Cancer development and immune defense, was recently awarded a grant from the Niels Stensen Fellowship. Since the 1960s, the Niels Stensen Fellowship has been awarded annually to outstanding researchers who recently received their PhD to enable them to gain research experience at a top university or institute abroad.

Jorieke will use this personal grant to fund a postdoc at École polytechnique fédérale de Lausanne (EPFL) in Lausanne, Switzerland. Here, she will work in the lab of Prof. Bastings to engineer DNA-based artificial T cells to study tolerance induced by dendritic cells.

Iris Nagtegaal and Nico Sommerdijk appointed members of the Academia Europaea

Iris Nagtegaal and Nico Sommerdijk were recently appointed members of the Academia Europaea, the European society of scientists who are among the world's top scientists.

The Academia Europaea gathers over two thousand scientists from Europe across the breadth of science. Each year, the most outstanding international candidates are selected.

Mara Nicolasen awarded the best Master thesis prize

The Master's thesis is a proof of the ability of a Master's student to perform scientific research and to present his/her findings in a clear and concise manner. Yearly RIMLS gives an award to the most outstanding Master's dissertation.

The winner of the RIMLS Master thesis: Mara Nicolasen Major Histocompatibility Complex- class I drives polarisation of the microtubule organizing center in dendritic cell synapses.

Jury report:

This master thesis studied the cellular processes that occur in dendritic cells after formation of an immunological synapse with a T cell. It was found that stimulation of MHC-I molecules on the dendritic cells leads to polarization of the cell’s cytoskeleton and organelles towards the immune synapse. The results obtained from the thesis provide a new insight of MHC-I as a receptor molecule. The work also contributes to the optimization of dendritic cell-based immunotherapies through a better understanding of the physiological events at the dendritic cell synapse. The thesis involved a wide range of cell biological and immunological techniques: from blood isolation of cells, flow cytometry, qPCR, Western blot to advanced microscopy. It was written with a clear structure and an in-depth discussion.

Rik Lindeboom received best PhD thesis award

The doctoral thesis is a proof of the ability of the PhD candidate to perform independent scientific research. Yearly RIMLS gives an award to the most outstanding thesis.

The winner of the RIMLS PhD thesis:  Rik Lindeboom Investigating gene regulation in development and disease using integrative omics approaches

Jury report:

This thesis consists of seven experimental chapters. So far, six have been published in the top journals, including Nature Genetics, Nature Structural and Molecular Biology, Developmental Cell, Cell Stem Cell and Molecular Systems Biology. The multi-omics strategies were applied in the thesis concerning computational analysis combined with biological assays. The work contributes to the fundamental understanding of gene regulation in a variety of different biological systems, such as embryonal development, stem cell differentiation and cancer. In one of the chapters, the candidate developed a new method to quantitatively study gene expression regulation in vivo, leading to a patent application. 

A Human Frontier Science Program grant for Johannes Textor

T Cell Crowd Control. Johannes Textor, Cancer development and immune defense. 
Awarded Radboudumc and Faculty of Science: 850 kEuro.

Johannes Textor, theme Cancer development and immune defense, has been awarded a program grant of 1 million US dollars by The Human Frontier Science Program (HFSP), together with his team members Judith Mandl (McGill University, Montreal, Canada) and Daniel Parisi (Buenos Aires institute of Technology, Argentina).

The T cells of the adaptive immune system are constantly on the move, can enter most tissues, and operate inlarge crowds. Millions of densely packed T cells roam the lymphatic organs  in search of foreign antigen while activated T cells divide vigorously and flock to tissues where they mount local immune responses to pathogens or cancer cells.

The HFSP project combines expertise in immunology, computational biology, and pedestrian dynamics to shed light how T cell crowds remain motile with such remarkable efficiency in many conditions and what it would take to disrupt their smooth flow.

HFSP grants are highly competitive awards intended for basic research at the frontier of human knowledge. They are open to applicants from all nations, and awardees are selected through a rigorous year-long review process. From more than 700 proposals that were initially submitted by scientists based in more than 50 different countries, only the top 4% were funded, and Johannes Textor's propasal was ranked third overall. Johannes Textor was the only scientist from a Dutch instutition to be selected.

Kolff startup grant Dutch Kidney Foundation for Marloes Michels

PERSPECTIV study PERSpectives for PErsonalization of Complement-directed Therapy in patients with C3 glomerulopathy. Marloes Michels, Renal disorders.
Awarded Radboudumc: 100 kEuro.

The Dutch Kidney Foundation supports talented postdocs and physician researchers through providing personal grants that support different phases of a research career. Kolff grant recipients are foreseen to make important contributions to the field of renal research and to stimulate the application of research results in practice.