‘ATP13A3 mutations in pulmonary arterial hypertension and dysregulated polyamine metabolism’
I am a Principal Research Associate in the Heart and Lung Research Institute at the University of Cambridge. My core research focusses on the loss of regulation of vascular stability and structure in disease, with particular focus on pulmonary arterial hypertension (PAH). I obtained my B.Sc. in Biochemistry from King’s College London and studied for my Ph.D. at Imperial College London. I moved to Cambridge in 2001 and began my studies into the impact of PAH-associated mutations in the BMPR2 gene, which encodes the bone morphogenetic protein type-II receptor (BMPR-II). My early studies focussed on characterising the functional roles of TGF and BMP receptors in smooth muscle cells and the cross-talk between these pathways. In the past 15 years, I have studied the roles of BMP9 and BMP10 in endothelial cells. My studies of BMP9 as a positive regulator of BMPR2 and a promoter of endothelial integrity underpinned the demonstration that exogenous BMP9 administration may represent a therapy for PAH. This contributed to the formation of the University start-up, Morphogen-IX Ltd, now part of Centessa Pharmaceuticals. As the PAH-associated gene mutations often show reduced penetrance, my studies extend to the interaction of potential modifier pathways with the BMP pathway.
‘Smooth muscle cell heterogeneity in vascular disease, one cell at a time’
The Jorgensen group studies how vascular smooth muscle cell (VSMC) plasticity and heterogeneity is regulated in vascular health and disease. Her team has demonstrated that a small number of pre-existing VSMC undergo extensive proliferative expansion to generate a large number of cell in atherosclerotic lesions and that similar clonal expansion is a hallmark of other vascular disease models. Using single cell transcriptome profiling, the group has revealed substantial VSMC heterogeneity both in lesions and in healthy arteries. These findings have implication for the understanding of VSMC behaviour and how selective targeting of disease-associated VSMC could be translated to the clinic. Helle was awarded a PhD in molecular biology from Aarhus University in 2000. During her postdoctoral training she studied epigenetic mechanisms (University of Edinburgh) and investigated impact on embryonic stem cell maintenance and cell fate choices (London Institute of Medical Research).
ROOM 88/89, GROUND FLOOR, HLRI
