Danielle Nicholson at Pintail Limited posed a set of questions to Professor Diether Lambrechts of the VIB about his research and career.
Can you give a tip or two to those aiming to become successful, leading academic researchers?
I believe that there are several ways you can become an academic research leader. The best tips I can give are not to give up, to believe in your own ideas and to have a passion for your own research. It is hard work to become known in a particular field, but the easiest way is often to publish a high-impact publication that becomes widely cited because then other scientists will get to know you and successful grant applications and applications for (inter)national collaborations will follow. In this regard, I consider it much more important to publish one very visible publication in a prestigious journal than several other publications in less prestigious journals with less visibility. Another important tip is to stay up to date with the literature and use the latest technologies on the market on unique sets of interesting patient samples, so you are the first to publish your research on a particular technology and set of samples in journals with a high impact factor. In my case, I apply the latest sequencing technologies and complex bioinformatics to samples obtained during phase 2-3 clinical trials and try to immediately transfer our results to clinical practice. To make all this possible, you obviously need to be connected to an environment that allows and supports your research. My lab is located on the campus of Biomedical Sciences at the University Hospital Leuven, which gives me easy access to clinical samples. My lab is affiliated with VIB, where I have early access to the latest technologies through their tech watch department.
What are some of the ways your research changed from 1999 to 2023?
My research group is focused on tackling important questions in oncology by translating genome-scale data sets into clinically applicable knowledge, by applying cutting-edge genome sequencing technologies and applied bioinformatics. In the first years of my research career, I mainly studied single-nucleotide polymorphisms and their role in cancer susceptibility. The volume of the datasets that we generated in these years was much much smaller. Nowadays, we use single-cell multi-omics profiling technologies to study similar research questions. The complexity of the data sets has grown enormously. We are now using big servers with lots of computing power, and we perform complex network analyses or use artificial intelligence methods to investigate our datasets. So over time, data analysis methods have become increasingly important. Nowadays, the majority of my lab members are actually dry-lab computational biologists.
Which of your career achievements make you feel most satisfied?
One of my most satisfying achievements is that I managed to translate my research findings into clinically meaningful findings. In 2012, my lab was among the first to perform whole-genome sequencing of solid tumours. We quickly observed how a specific mutational scar was present in microsatellite unstable tumours. This scar was patented and exclusively licensed to Biocartis NV (Mechelen, Belgium). Following an intense collaboration with Biocartis, a 7-marker assay fully compatible with the Idylla platform was launched in 2018 to detect microsatellite instability (MSI). Idylla™ MSI is nowadays the only MSI test that already received CE-IVD clearance, and it is distributed on a worldwide scale (sub-licenced to Wondfo in China and Nichirei Biosciences in Japan). In 2018, the FDA approved checkpoint immunotherapy as the first cancer treatment for any solid tumour with a specific genetic feature (MSI). Currently, Idylla™ MSI is used in 2 registration studies from Bristol-Myers-Squib to seek FDA registration of the test as a companion diagnostic. Another achievement that makes me proud is that we were among the first to characterize heterogeneity within the tumour microenvironment (TME) by single-cell RNAseq (scRNAseq). For instance, we described the first single-cell atlas of the lung TME (Lambrechts, Nat Med 2018) and compared TME heterogeneity across several cancer types (Qian, Cell Res 2020). We also explored by scRNAseq how TME heterogeneity predicts response immune checkpoint blockade and dynamically alters during treatment (Bassez, Nat Med, 2021). Single-cell phenotyping of bronchoalveolar lavages from COVID-19 patients revealed similar diversity as in tumours, identifying novel immunophenotypes and associated mechanisms underlying critical disease (Wauters, Cell Res 2021). These single-cell studies have generated a lot of visibility to our lab. Consequently, I was awarded an ERC advanced grant in 2023 that allows me to continue my research at a high level of excellence with my fantastic multidisciplinary team and collaborations.
In your opinion, what is most exciting about cancer research today? What has enabled this progress? What is necessary to progress this further?
Over the past decade, we have made tremendous progress in understanding cancer mechanisms and cancer therapies, thanks in part to state-of-the-art high-resolution technologies such as single-cell technologies, and doing translational research in a phase 2-3 cancer clinical trial by applying these new technologies to the samples obtained during the trial. I think it is important to include translational research in the study protocol from the beginning when starting a clinical trial. The technologies/methods are becoming increasingly sophisticated and the application of these technologies to large groups of multicenter clinical trial cancer samples will provide many more insights into cancer biology and identify reliable biomarkers to stratify patients for appropriate therapy, preventing serious side effects and saving costs. This can be a success story if we collaborate with different teams, each with their own expertise and access to clinical samples, such as in the COLOSSUS collaboration.
How is COLOSSUS important to the Center for Cancer Biology at the VIB?
Collaborative projects such as COLOSSUS are important for cutting-edge research. An international multidisciplinary collaborative project brings together several world-renowned groups, each with their own expertise and samples to apply advanced technologies and complex analyses to samples from clinical cancer trials. COLOSSUS is a follow-up study to an earlier European project (Angiopredict) that provided important insights into colorectal cancer. Angiopredict proved that when groups work together in a complementary effort, they make the most of each group’s expertise. And of course, one can also use the relationships and friendships that you build during such projects later on within other research collaborations.
What do you like to do in your free time?
Besides doing research, which is also a hobby for me, I love to spend time biking and running. In 2020 I bought a gravel bike and together with friends I now regularly make epic bike rides through nature in Belgium, France and Germany. And after a full day of doing sports, I obviously like to enjoy a couple of Belgian beers.