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Cambridge Cardiovascular

Vascular smooth muscle cell diversity
Gene regulation


My focus is on the regulation of cell plasticity in the cardiovascular system and how this is perturbed in disease. In particular, we study vascular smooth muscle cells (VSMC) and how they 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.

We study how these gene expression programs are regulated and impact on phenotypic plasticity in development, tissue homeostasis and disease models.


Key publications: 

Clement, M.*/Chappell, J.*, Raffort, J., Lareyre, F., Vandestienne, M., Taylor, A.L., Finigan, A., Harrison, J, Bennett, M.R., Taleb,S., Jorgensen, H.F.#/Mallat, Z#. Vascular Smooth Muscle Cell Plasticity and Autophagy in Dissecting Aortic Aneurysms. *Joint first authors. #Joint last authors. ATVB online first

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 Communications9, 4567. *Joint first authors. #Joint last authors.

Jmjd2c/Kdm4c facilitates the assembly of essential enhancer-protein complexes at the onset of embryonic stem cell differentiation. Tomaz RA, Harman JL, Karimlou D, Weavers L, Fritsch L, Bou-Kheir T, Bell E, Torres ID, Niakan KK, Fisher C, Joshi O, Stunnenberg HG, Curry E, Ait-Si-Ali S, Jørgensen HF, Azuara V. Development. 2017 Feb 15;144(4):567-579.

Extensive Proliferation of a Subset of Differentiated, Yet Plastic, Medial Vascular Smooth Muscle Cells Contribute to Neointimal Formation in Mouse Injury and Atherosclerosis Models. Chappell J, Harman JL, Narasimhan VM, Yu H, Foote K, Simons BD, Bennett MR and Jørgensen HF. Circ Res. 2016 Dec 9;119(12):1313-1323.

Transcriptional Mechanisms of Proneural Factors and REST in Regulating Neuronal Reprogramming of Astrocytes. Masserdotti G, Gillotin S, Sutor B, Drechsel D, Irmler M, Jørgensen HF, Sass S, Theis FJ, Beckers J, Berninger B, Guillemot F, Götz M. Cell Stem Cell. 2015 Jul 2;17(1):74-88.

Modeling of epigenome dynamics identifies transcription factors that mediate Polycomb targeting. Arnold P, Schöler A, Pachkov M, Balwierz PJ, Jørgensen H, Stadler MB, van Nimwegen E, Schübeler D. Genome Res. 2013 Jan;23(1):60-73.

Embryonic stem cell-derived hemangioblasts remain epigenetically plastic and require PRC1 to prevent neural gene expression. Mazzarella L, Jørgensen HF, Soza-Ried J, Terry AV, Pearson S, Lacaud G, Kouskoff V, Merkenschlager M, Fisher AG. Blood. 2011 Jan 6;117(1):83-7.

Can controversies be put to REST? Jørgensen HF, Fisher AG. Nature. 2010 Sep 2;467(7311):E3-4.

Jarid2 is a PRC2 component in embryonic stem cells required for multi-lineage differentiation and recruitment of PRC1 and RNA Polymerase II to developmental regulators. Landeira D, Sauer S, Poot R, Dvorkina M, Mazzarella L, Jørgensen HF, Pereira CF, Leleu M, Piccolo FM, Spivakov M, Brookes E, Pombo A, Fisher C, Skarnes WC, Snoek T, Bezstarosti K, Demmers J, Klose RJ, Casanova M, Tavares L, Brockdorff N, Merkenschlager M, Fisher AG. Nat Cell Biol. 2010 Jun;12(6):618-24.

LOCKing in Cellular Potential. Jørgensen HF, Fisher AG. Cell Stem Cell. 2009 Mar 6;4(3):192-4.

Is REST required for ESC pluripotency? Jørgensen HF, Chen ZF, Merkenschlager M, Fisher AG. Nature. 2009 Feb 26;457(7233):E4-5.

REST selectively represses a subset of RE1-containing neuronal genes in mouse embryonic stem cells. Jørgensen HF, Terry A, Beretta C, Pereira CF, Leleu M, Chen ZF, Kelly C, Merkenschlager M, Fisher AG. Development. 2009 Mar;136(5):715-21.

A novel CpG island set identifies tissue-specific methylation at developmental gene loci. Illingworth R, Kerr A, Desousa D, Jørgensen H, Ellis P, Stalker J, Jackson D, Clee C, Plumb R, Rogers J, Humphray S, Cox T, Langford C, Bird A. PLoS Biol. 2008 Jan;6(1):e22. doi: 10.1371/journal.pbio.0060022.

The impact of chromatin modifiers on the timing of locus replication in mouse embryonic stem cells. Jørgensen HF, Azuara V, Amoils S, Spivakov M, Terry A, Nesterova T, Cobb BS, Ramsahoye B, Merkenschlager M, Fisher AG. Genome Biol. 2007;8(8):R169.

Stem cells primed for action: polycomb repressive complexes restrain the expression of lineage-specific regulators in embryonic stem cells. Jørgensen HF, Giadrossi S, Casanova M, Endoh M, Koseki H, Brockdorff N, Fisher AG. Cell Cycle. 2006 Jul;5(13):1411-4.

Chromatin signatures of pluripotent cell lines. Azuara V, Perry P, Sauer S, Spivakov M, Jørgensen HF, John RM, Gouti M, Casanova M, Warnes G, Merkenschlager M, Fisher AG. Nat Cell Biol. 2006 May;8(5):532-8.

Associate Professor
University Lecturer in Stem Cell and Developmental Biology


Person keywords: 
single-cell RNA sequencing
vascular smooth muscle cells (VSMC)
gene expression profiling
functional genomics
vascular biology
cardiovascular disease
stem cells
Aortic aneurysm