Professor Ron M.A. Heeren

My name's Ron Heeren. I'm a distinguished professor of molecular imaging at Maastricht University in the Netherlands, and I am the director of the Maastricht MultiModal Molecular Imaging Institute, M4i. We are working on imaging mass spectrometry and imaging mass spectrometry in pathology. And the reason we are doing this is because we want to help the pathologists make their diagnoses more precise. Very often, the pathology diagnosis is based on morphology, the shape and the density of cells. And we add a level of molecular information in that. And right now, the big challenge is integrating many different levels of molecular information, and that's why our institute is also called the Multimodal Molecular Institute. There are many application areas of imaging mass spectrometry, but one example, specifically, is our work on breast cancer. And one of the recent technologies now allows us to go down to single cells. So, we can look at single cells in a piece of breast cancer from a patient, define the molecular patterns that predict response to a therapy or define the stage of a tumor. And that's exactly the heart of why imaging mass spectrometry is so important. Our breast cancer work is done in close collaboration with Johns Hopkins University and the instrumentation companies, like Bruker, and Waters, and Thermo. We work with all of them, and I think that's really key of what is going on now, interdisciplinary collaborations. You need to bring the right people together to tackle these very, very complex questions. In particular, our collaboration with Kristine Glunde at Johns Hopkins has, you know, for the last 10 years really helped us to gain deep insight into the biology and the molecular biology of hypoxia in the breast cancer, so this is about tumor micro-environments. And micro-environment is really important, specifically now that we can look at single cells. Single cells are great, but if you look at a cell out of context, it's meaningless piece of information. Our capabilities to look at single cells in the context of a tissue also help us to understand how these tumor cells respond to a changing environment. And that is exactly what we're studying together with Hopkins, with the help of all the mass spectrometry vendors. So, one of the things that we are looking for is detailed metabolic lipids or protein profiles of an individual cell to understand this molecular biology in the context of the tissue. The technologies that have been developed over the last year, two years or so, have allowed us, one, to go down to very high spatial resolution, for instance, with the microGRID that Bruker's introducing at ASMS that really helps us to go down to 5 micron, which means that we can do molecular analysis within a single cell. And the other thing that has been really revolutionizing the last year, actually the last half year, is the ability to do also targeted proteomics, making use of labeled antibodies with the imaging probes. The combination of the two is incredibly strong because you can do these analyses on exactly the same tissue. So, think about this, you get lipidome images, you get proteome images, at single-cell resolution, in the context of a very relevant disease. Now, those are the technology developments, that's where it's brought us now. The reason we're collaborating with pathologists, surgeons, and other medical professionals is because we want our work to be impactful. And, if we develop technologies, we are a little bit on an island. We can develop great microscopes that look into molecular detail of a single cell, but if we're not translating that to the medical professions, then it's meaningless, it's not impactful. So, by starting these collaborations, we actually help to increase the impact of our work. So, one of the reasons we focus on single cells in context is to build an atlas of every single cell in the body. And we have a close collaboration with the Technical University of Munich, of the Institute of Immunology, where we try to identify immune cells. But particularly, how do immune cells respond to disease stimuli or disease signals? And so, by being able to look at an individual cell in the context of a tissue, we can actually figure out how a disease cell recruits other immune cells to actually fight the disease. Our single-cell capabilities provide us the molecular insights to understand the fundaments of the immunology response. So, the future of imaging mass spectrometry, I think, lies in digital pathology. Because the amount of information we're providing is very difficult to grasp for a pathologist, so what we need to do is make sure that that information is available in an environment they're comfortable with. And those are the digital pathology platforms. So, with the vendors, we'll be working to integrate the layers of molecular information in these digital pathology platforms. And that's going to be a major step forward in the future. The second aspect of the future, I think, is improving spatial resolution. Because as we go down in pixel size in our mass spectrometers, we can start to fantasize about doing imaging mass spectrometry at subcellular levels. And then we can look at the context of an organelle in its cell and how it responds to the environments.