The ultimate goal of the Mechano·Control project is to be able to abrogate breast tumour progression. To do that, it is very important to apply the Mechano·Control findings at different scales, from single molecules and all the way up to the organism and patient level. For that, Thijs Koorman, a senior postdoc at the DerksenLab at the UMC Utrecht, will perform fundamental and preclinical research within in the Mechano Control project. His main goal is to translate basic findings with therapeutic potential to target invasive breast cancer. With this interview, we are going to take a step forward and get a closer look to the animal and human models, the largest scale of the Mechano·Control consortium.
Dr. Thijs Koorman runs a variety of different tasks. But first, let’s get to know a little bit more about their role in the Mechano·Control consortium. The main aim within the DerksenLab is to translate the molecular findings within the Mechano·Control project to animal and human models of invasive breast cancer. This group has a fundamental to translational focus. They provide proof of concept in preclinical models of breast cancer and test novel candidate targeted therapeutic interventions identified within Mechano·Control.
With this in mind, Thijs together with Dr. Daan Visser (technician within the Mechano Control consortium) test the therapeutic potential of the identified molecules in the consortium with the hope to obtain pre-clinical data that can be used to ultimately better treat patients suffering from invasive breast cancer.
And how is this translated into the lab?
“We culture mouse and human organotypic cancer models in both 2D and 3D. The models used represent the two types of invasive breast cancer. As such, they harbour all aspects of human invasive breast cancer, which we study using molecular biochemistry and microscopy”, explains Thijs.
In particular, Thijs studies the molecular and signalling composition of cell adhesion proteins and how disruption of this complex potentiates oncogenic signalling. For this he uses 2D and 3D organotypic tumor models and preclinical mouse models of invasive breast cancer. The group has a deep interest in how loss of mechano-transducing cell-cell and cell-matrix contacts drive to invasive breast cancers, focussing on lobular carcinoma. The groups has generated a breast cancer sample database of over 2000 patients and collected tumour material of over >1000 patients to test molecular markers.
Until now, Thijs and the researchers at the Derksen Lab have discovered a molecular mechanism that explains how invasive breast cancer cells may stop dividing and linger in the body for years and what triggers expansion at the metastatic site. Now, they are probing how to target these “sleeping cells” during dissemination and stop the growing cells with therapeutics.
Discovery-based fundamental science is essential to establish the building blocks of therapeutic interventions. “We aim to bridge both aspects, understanding the molecular signalling and discovering or identifying the means to target them. Most importantly, we have the tools to test such in our clinical mouse models and all subtypes of invasive breast cancer. Being able to make these translational steps fast and efficient is a unique aspect of our work” says Thijs.
Thijs also supports the day-to-day supervision of bachelor, master and the Ph.D. students. He also teaches a variety of undergraduate classes at Utrecht University. Thijs also manages the clinical outsourcing and dissemination, including patient advocate involvement. Thijs also holds a leadership position within the COST Action Lobsterpot (CA19138), an initiative of the European Lobular Breast Cancer Consortium (www.elbcc.org).
According to Thijs, being a part of the Mechano·Control consortium is a thrill and a great opportunity to work with colleagues all over the world that work at very different scales. “A single email, text or conversation is sufficient to spark new ideas or endeavours. Combining all of our skills and thinking outside the box is exciting. Not only for your own development, but also to obtain new views on scientific problems. We have a collaborative spirit and were able to test a lot of hypotheses which otherwise would not have been tested.”