The key to the right treatment
Professor Selbach, Dr. Coscia, you and your Berlin partners launched the MSTARS research project three years ago. Now the German Federal Ministry of Education and Research (BMBF) has granted funding for another three years. The Max Delbrück Center is set to receive over €1.3 million of that. Could you just remind us of your overarching goal for MSTARS?
Matthias Selbach: Basically, we want to find out why some therapies work very well in some patients but have no effect in others – even though the diseased tissue is more or less genetically identical. To do that, we use mass spectrometry, a method that allows us to determine exactly how the patients’ cells differ from one another. We can see, for instance, which genes are actually transformed into proteins.
We’re hoping this will help us discover biomarkers that can accurately predict the success of a therapy. This knowledge would directly benefit physicians, because it would allow them to select or reject a specific therapy based on the individual characteristics of their patient.
Focusing on cancer and inflammation
Which diseases are you looking at first?
Fabian Coscia: At the moment, we’re mainly examining various types of cancerous tissue. The cancers include squamous cell carcinoma of the head and neck, leukemia, neuroblastoma, and breast, ovarian, and prostate cancers. We also want to increase our focus on inflammatory diseases such as myocarditis, which is swelling of the heart muscle, and chronic liver diseases.
Also, because the coronavirus pandemic started more or less at the same time as MSTARS, we unexpectedly ended up devoting a lot of attention to COVID-19. By studying the proteins present in infected cells, we discovered why some people fall seriously ill. In those cases, the virus enters specific immune cells and reprograms them so they can no longer perform their usual functions.
A Swiss Army knife for molecular biologists
What makes the technology you use so special?
Matthias Selbach: Mass spectrometry is a unique method that allows us to weigh molecules and identify them by their weight. We can use it to systematically study proteins and other substances involved in the development or progression of diseases. So we’re not looking for specific molecules as you would with, say, a COVID-19 test; we’re interested in changes on a very broad scale.
Our goal is to analyze an organism, a tissue, or even an individual cell in its entirety so we can better understand diseases and therapeutic resistance. Mass spectrometry is a really versatile method – in fact, it’s a bit like a Swiss Army knife for molecular biologists.
What goals have you achieved in the past three years?
Fabian Coscia: In my lab, we established a method called Deep Visual Proteomics, which allows us to map the proteins present in tumor tissue and study them at an unprecedented level of detail. The method combines state-of-the-art microscopy and laser techniques with mass spectrometry and artificial intelligence. It provides us with unparalleled insight into the pathological processes of cancer.
In coronavirus research, a mass spectrometry analysis of roughly 7,000 proteins showed that SARS-CoV-2 prompts the immune system’s macrophages to produce signaling that causes scarring of the lung tissue.
Matthias Selbach: That said, the first funding phase of MSTARS was mainly about getting the necessary structures in place, inducting new team members, and building networks with our partners, such as the physicians at Charité. The project has also created much closer ties between the Berlin research teams who work with mass spectrometry.
MSTARS brings proteomics to the clinic
What will change in the second round of MSTARS?
Fabian Coscia: We’ll increasingly be working on establishing work flows that can be routinely used in precision medicine in Berlin and beyond. The first step will be to begin following uniform standards for taking and storing tissue and blood samples from patients.
Here at the Max Delbrück Center, we’re primarily interested in proteins, which are the functionaries of cells. Other groups are looking at lipids and metabolites. The first clinical trials should also mean that patients will soon start benefiting from our findings. We definitely want to further increase our focus on cancer so we can better understand and predict resistance to chemo- and immunotherapies.
Within MSTARS, you collaborate with Charité – Universitätsmedizin Berlin, the Max Planck Institute for Molecular Genetics, and Humboldt Universität zu Berlin. How does the Max Delbrück Center benefit from this alliance?
Matthias Selbach: MSTARS has strengthened the research landscape in Berlin, because it has created very good links between scientific and clinical research groups. To answer the questions we pose at the Max Delbrück Center, we need to be able to access clinical samples. Our partnership with Charité has proven especially helpful for this. The funding also allowed us to recruit Fabian Coscia, an outstanding scientist, as head of a junior research group here at the Max Delbrück Center.
Reliable findings with very small samples
Which parts of the MSTARS project will the Max Delbrück Center be most involved in?
Matthias Selbach: One key area will be the Deep Visual Proteomics method that Fabian developed. Our aim is to gain a mechanistic understanding of diseases. We’re not interested in just producing long lists of proteins that are present in tissue and bodily fluids and might be useful for a diagnosis. We really want to learn how diseases emerge at the molecular level – and then use that knowledge for therapies. We’re also continually working to increase the sensitivity of mass spectrometry so we can produce reliable findings even with very small samples.
Is there a particular research question that you personally hope will be solved in the next three years?
Fabian Coscia: I’m really excited to see the results of several studies we’re currently running. We know, for instance, that the success of an immunotherapy depends on the way various immune cells interact with each other and with the tumor cells. Deep Visual Proteomics will allow us to pinpoint the part of the tumor where the cells are especially densely packed and the extent to which this changes the proteome – the totality of all proteins formed in cells. That should help us understand why immunotherapies sometimes work well and other times not so well. It looks like we’ll receive the first batch of data for this in the next six months. A breast cancer study is also underway and I’m excited to see those results, too.
Matthias Selbach: Overall, I hope the findings we produce about the molecular processes in tumor cells lead to truly individual treatment options. My wish is that mass spectrometry examinations of tumor tissue will eventually allow physicians to precisely assess which combination of chemotherapies is most likely to cure a patient.
Anke Brodmerkel conducted the interview.
- Press release: Creating protein maps of tumors
- Press release Mass spectrometry for precision medicine
- MSTARS website
Berlin-based project MSTARS (Multimodal Clinical Mass Spectrometry to Target Treatment Resistance) has, since March 1, 2020, been supported by the BMBF as part of its MSCoreSys (Research Cores for Mass Spectrometry in Systems Medicine) funding scheme. MSTARS is one of four research cores chosen by the BMBF; the other three are located in Heidelberg, Mainz, and Munich.
Funding was initially approved for three years. During this period, the Max Delbrück Center received almost €2.9 million. The BMBF provided another nearly €2.8 million for the establishment of Dr. Fabian Coscia’s Spatial Proteomics Lab. The second three-year funding phase began on March 1, 2023. During this period, more than €1.3 million will go to the Max Delbrück Center, while Charité will receive around €3 million.
The project is led by four coordinators: Professor Matthias Selbach, head of the Proteome Dynamics Lab at the Max Delbrück Center; Professor Ulrich Keilholz, director of the Charité Comprehensive Cancer Center (CCCC); Professor Markus Ralser, director of Charité’s Institute of Biochemistry; and Professor Frederick Klauschen, head of the Systems Pathology Lab at Charité’s Institute of Pathology.