Helle Jørgensen
Associate Professor
Email: hfj22@cam.ac.uk
Twitter: hfj22@cam.ac.uk
LinkedIn: www.linkedin.com/in/helle-f-jørgensen-1a15328
Biography and research:
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 their impact on embryonic stem cell maintenance and cell fate choices (London Institute of Medical Research).
Research Approach:
Our group investigates the regulation of cell plasticity in the cardiovascular system and how this is perturbed in disease. In particular, we study vascular smooth muscle cells (VSMCs) and how these cells contribute to the development of atherosclerosis, the disease underlying heart attack and stroke. VSMCs exist in a contractile, quiescent state in healthy arteries, but can downregulate this phenotype in response to injury and inflammation. The resulting de-differentiated state is characterised by widespread changes in gene expression leading to perturbed extracellular matrix remodelling, proliferation and migration. Using single cell approaches, lineage tracing and global epigenetic profiling, we study how these gene expression programs are regulated and impact on phenotypic plasticity in genetic disease models and human tissue.
Selected Publications:
- Lambert, J., Oc, S., Worssam, M. D., Häußler, D., Figg, N. L., Baxter, R., Foote, K., Finigan, A., Mahbubani, K. T., Bennett, M. R., Krüger, A., Spivakov, M., & Jørgensen, H. F. (2023). Network-based prioritisation and validation of novel regulators of vascular smooth muscle cell proliferation in disease. BioRxiv, 2023.08.25.554834. https://doi.org/10.1101/2023.08.25.554834
- Worssam, M. D., Lambert, J., Oc, S., Taylor, J. C., Taylor, A. L., Dobnikar, L., Chappell, J., Harman, J. L., Figg, N. L., Finigan, A., Foote, K., Uryga, A. K., Bennett, M. R., Spivakov, M., & Jørgensen, H. F. (2022). Cellular mechanisms of oligoclonal vascular smooth muscle cell expansion in cardiovascular disease. Cardiovascular Research. https://doi.org/10.1093/cvr/cvac138
- Clément, M., Chappell, J., Raffort, J., Lareyre, F., Vandestienne, M., Taylor, A. L., Finigan, A., Harrison, J., Bennett, M. R., Bruneval, P., Taleb, S., Jørgensen, H. F., & Mallat, Z. (2019). Vascular Smooth Muscle Cell Plasticity and Autophagy in Dissecting Aortic Aneurysms. Arteriosclerosis, Thrombosis, and Vascular Biology, 39(6), 1149–1159. https://doi.org/10.1161/atvbaha.118.311727
- Dobnikar, L., Taylor, A. L., Chappell, J., Oldach, P., Harman, J. L., Oerton, E., Dzierzak, E., Bennett, M. R., Spivakov, M., & Jørgensen, H. F. (2018). Disease-relevant transcriptional signatures identified in individual smooth muscle cells from healthy mouse vessels. Nature Communications, 9(1), 4567. https://doi.org/10.1038/s41467-018-06891-x
- Chappell, J., Harman, J. L., Narasimhan, V. M., Yu, H., Foote, K., Simons, B. D., Bennett, M. R., & Jørgensen, H. F. (2016). Extensive Proliferation of a Subset of Differentiated, yet Plastic, Medial Vascular Smooth Muscle Cells Contributes to Neointimal Formation in Mouse Injury and Atherosclerosis Models. Circulation Research, 119(12), 1313–1323. https://doi.org/10.1161/circresaha.116.309799
Further information
http://www.med.cam.ac.uk/jorgensen/
https://www.cardiovascular.cam.ac.uk/directory/hjorgensen
