Maria H Ulvmar 2016-2018

Maria Ulvmar is awarded the M L Philipson prize and grant for research on the lymph node vascular specialization in regulation of anti-tumour immune responses and metastasis. Her research has potential to identify new molecular targets for immune therapy and ways to interfere with the mechanisms that are involved in cancer metastasis.

After her PhD in cancer biology from Karolinska Institutet, Maria Ulvmar was awarded a Marie Curie IE fellowship 2011 to pursue postdoctoral studies at the Centre for Immune Regulation at Birmingham University, UK, in the group of Professor Antal Rot. After a short second post doc in Sweden she is now establishing her own research group at the Department of Immunology, Genetics and Pathology (IGP), Uppsala University. Her research bridges vascular biology and tumour immunology, by asking questions about the role of the lymph node vascular specialization and heterogeneity in regulation of anti-tumour immune responses and metastasis.

The core of my research interest has always been a strong ambition to understand how the immune system is regulated by non-hematopoietic cells. 

During my PhD with Prof. Rune Toftgård, I demonstrated that TNF cytokine signaling in skin keratinocytes drives skin inflammation and cancer elicited by inhibition of the transcription factor NF-B. These results were against the current dogma, which told that the effects of TNF were mediated mainly through immune cells. The finding that also non-immune cells have critical roles in inflammatory and immune responses inspired me to continue to study the role of non-hematopoitic cells in immune regulation. I took my interest a further step during my postdoctoral Marie Curie fellowship when I identified a paradigmatic mechanism for chemokine gradient formation in the lymph node through expression of the atypical chemokine receptor CCRL1 (ACKR4), on a previously unknown subset of lymphatic endothelial cells. We also showed that expression of CCRL1 is necessary for efficient chemokine-guided entry of dendritic cells into the lymph node. The work was published in the prestigious journal Nature Immunology. Our data demonstrated, unexpectedly, that even adjacent endothelial cell layers of the same sinus can adopt distinct molecular phenotypes and functions. For me, two important scientific insights from these studies were that endothelial cells not only define structural but also molecular borders in the tissues and that they actively participate in immune regulation in ways we have only begun to understand. After I finished my fellowship, I sought to find a scientific environment where I could develop my interest in endothelial cell biology. The vascular biology centre at IGP was just the environment I was looking for and I joined the lymphatic vessel developmental group of Dr. Taija Mäkinen to bridge the time between my fellowship and establishing an independent group, and to gain new knowledge and tools for the study of endothelial cell biology. 

While proliferation and morphological changes of vessels in the context of cancer and tumour metastasis has gained a lot of attention for several years, the understanding of the molecular patterning and the functional specialization of the vessels is lagging behind. I strongly feel that this gap in the current knowledge needs to be addressed. My focus is the unique vasculature of the lymph node. The lymph nodes have essential roles in adaptive immune responses, including anti-tumour immune responses, and are major sites for cancer metastasis. 

My group will work in the technical forefront of multicolour cell analysis and cell sorting, using combinations of lineage tracing and staining for endothelial cell subtypes that allow us to isolate and expression-profile unique subsets of endothelial cells in ways that have not been done before. This will be combined with advanced 3D imaging and state-of-the-art genetic models that allow us to evaluate gene functions specifically in endothelial cells. We will work with experimental models but will importantly correlate experimental data to expression patterns in human tumour draining lymph nodes, to be able to select molecular targets of therapeutic relevance. 

It is a true privilege to work as a scientist. I am not from an academic background and have worked outside of science before I started to study biomedicine. Perhaps this makes me value this profession even higher. It is a great satisfaction when I also manage to confer my enthusiasm both for the subject and for the arts of learning and exploring, to my students. 

To receive the Malin and Lennart Philipson prize and award is a great honour and gives me the best possible start for my independent research career. The funding allows me to expand my research group, which will be vital for the results we can produce over the next coming years. The association of the prize and grant with Lennart Philipson’s name gives it a value that goes far beyond the monetary aspect. Lennart Philipson as a person and his work represents in many ways what we all should strive for as scientists; to work in the research forefront, both conceptually and methodologically, combined with courage and strong leadership. I never had the privilege to meet Lennart Philipson but I have read about his career and work with high interest. Few Swedish scientists have accomplished what he did during his career and he is a true inspiration.