Oxford's cancer community is delighted to welcome Professor Stefan Constantinescu, a physician scientist and authority on the signalling pathways and molecular mechanisms of blood cancers, especially myeloproliferative neoplasms, a collection of slow growing blood cancers that can progress to acute malignancies. He is a member of the Ludwig Institute for Cancer Research, Professor of Cell Biology at the Université catholique de Louvain, Director of Research (Honorary) at the Fonds National de la Recherche Scientifique (FRS-FNRS), Belgium and President of the Federation of European Academies of Medicine (FEAM). Constantinescu will spend 25% of his time at the Ludwig Oxford Branch and the remainder of the time at his existing Ludwig laboratory in Brussels.
Constantinescu has received many honors for his work, including membership of the Royal Academy of Medicine of Belgium and the Belgian Government prize for basic medical sciences. He is internationally known for his groundbreaking contributions to our understanding of the mutations and mechanisms that drive myeloproliferative disorders. In a fruitful collaboration with William Vainchenker, he discovered that a mutation (V617F) in a signalling enzyme named Janus kinase 2 (JAK2) occurs in most patients with polycythemia vera, in which red blood cells accumulate abnormally. Constantinescu’s subsequent work demonstrated how this mutation causes disease, leading to the development of novel therapies to treat myeloproliferative disorders and the widespread clinical use of genetic tests to detect the mutation.
Constantinescu has also identified and characterised other common mutations in the thrombopoietin receptor that cause these blood disorders. He has further demonstrated that mutated calreticulins –“chaperone” proteins that otherwise help fold other proteins appropriately—can induce myeloproliferative disorders via abnormal activation of the thrombopoietin receptor, identifying a novel oncogenic mechanism. His discoveries have helped transform the field and continue to open new avenues for the development of targeted therapies.
Constantinescu’s Ludwig Oxford lab will focus on a systematic study of signalling and epigenetic regulation during oncogenesis in chronic myeloid cancers and their progression to the severe condition, secondary acute myeloid leukaemia. Ludwig Oxford’s research programme will be enhanced by Constantinescu’s presence, and his own research programme will benefit from Ludwig Oxford’s expertise in cancer epigenetics, represented by the laboratories of Yang Shi, Chunxiao Song, Skirmantas Kriaucionis and Benjamin Schuster-Böckler.