Professional Education

  • Ph.D., University of Edinburgh, Cardiovascular Science
  • M.Sc. (MedSci), University Of Glasgow, Cardiovascular Sciences
  • B.Sc., University Of Aberdeen, Physiology

Stanford Advisors

All Publications

  • From novel discovery tools and biomarkers to precision medicine - basic cardiovascular science highlights of 2021/2022. Cardiovascular research Evans, P. C., Davidson, S. M., Wojta, J., Back, M., Bollini, S., Brittan, M., Catapano, A. L., Chaudhry, B., Cluitmans, M., Gnecchi, M., Guzik, T. J., Hoefer, I., Madonna, R., Monteiro, J. P., Morawietz, H., Osto, E., Padro, T., Sluimer, J. C., Tocchetti, C. G., Van der Heiden, K., Vilahur, G., Waltenberger, J., Weber, C. 2022


    Here we review the highlights of cardiovascular basic science in published in 2021 and early 2022 on behalf of the European Society of Cardiology Council for Basic Cardiovascular Science. We begin with non-coding RNAs which have emerged as central regulators cardiovascular biology, and then discuss how technological developments in single-cell 'omics are providing new insights in cardiovascular development, inflammation and disease. We also review recent discoveries on the biology of extracellular vesicles in driving either protective or pathogenic responses. The Nobel Prize in Physiology or Medicine 2021 recognised the importance of the molecular basis of mechanosensing and here we review breakthroughs in cardiovascular sensing of mechanical force. We also summarise discoveries in the field of atherosclerosis including the role of clonal haematopoiesis of indeterminate potential, and new mechanisms of cross-talk between hyperglycemia, lipid mediators and inflammation. The past 12 months also witnessed major advances in the field of cardiac arrhythmia including new mechanisms of fibrillation. We also focus on inducible pluripotent stem cell (iPSC) technology which has demonstrated disease causality for several genetic polymorphisms in long QT syndrome and aortic valve disease, paving the way for personalized medicine approaches. Finally, the cardiovascular community has continued to better understand COVID-19 with significant advancement in our knowledge of cardiovascular tropism, molecular markers, the mechanism of vaccine-induced thrombotic complications and new anti-viral therapies that protect the cardiovascular system.

    View details for DOI 10.1093/cvr/cvac114

    View details for PubMedID 35899362

  • Single-cell RNA-seq profiling of mouse endothelial cells in response to pulmonary arterial hypertension. Cardiovascular research Rodor, J., Chen, S., Scanlon, J. P., Monteiro, J. P., Caudrillier, A., Sweta, S., Stewart, K. R., Shmakova, A., Dobie, R., Henderson, B. E., Stewart, K., Hadoke, P. W., Southwood, M., Moore, S. D., Upton, P. D., Morrell, N. W., Li, Z., Chan, S. Y., Handen, A., Lafyatis, R., de Rooij, L. P., Henderson, N. C., Carmeliet, P., Spiroski, A., Brittan, M., Baker, A. H. 2021


    AIMS: Endothelial cell dysfunction drives the initiation and pathogenesis of pulmonary arterial hypertension (PAH). We aimed to characterise endothelial cell (EC) dynamics in PAH at single-cell resolution.METHODS AND RESULTS: We carried out single-cell RNA sequencing (scRNA-seq) of lung ECs isolated from an EC lineage-tracing mouse model in Control and SU5416/Hypoxia-induced PAH conditions. EC populations corresponding to distinct lung vessel types, including two discrete capillary populations, were identified in both Control and PAH mice. Differential gene expression analysis revealed global PAH-induced EC changes that were confirmed by bulk RNA-seq. This included upregulation of the major histocompatibility complex class II pathway, supporting a role for ECs in the inflammatory response in PAH. We also identified a PAH response specific to the second capillary EC population including upregulation of genes involved in cell death, cell motility and angiogenesis. Interestingly, four genes with genetic variants associated with PAH were dysregulated in mouse ECs in PAH. To compare relevance across PAH models and species, we performed a detailed analysis of EC heterogeneity and response to PAH in rats and humans through whole-lung PAH scRNA-seq datasets, revealing that 51% of up-regulated mouse genes were also up-regulated in rat or human PAH. We identified promising new candidates to target endothelial dysfunction including CD74, the knockdown of which regulates EC proliferation and barrier integrity in vitro. Finally, with an in silico cell ordering approach, we identified zonation-dependent changes across the arteriovenous axis in mouse PAH and showed upregulation of the Serine/threonine-protein kinase Sgk1 at the junction between the macro- and micro-vasculature.CONCLUSIONS: This study uncovers PAH-induced EC transcriptomic changes at a high resolution, revealing novel targets for potential therapeutic candidate development.

    View details for DOI 10.1093/cvr/cvab296

    View details for PubMedID 34528097

  • MIR503HG Loss Promotes Endothelial-to-Mesenchymal Transition in Vascular Disease. Circulation research Monteiro, J. P., Rodor, J., Caudrillier, A., Scanlon, J. P., Spiroski, A., Dudnakova, T., Pfluger-Muller, B., Shmakova, A., von Kriegsheim, A., Deng, L., Taylor, R. S., Wilson-Kanamori, J. R., Chen, S., Stewart, K., Thomson, A., Mitic, T., McClure, J. D., Iyinikkel, J., Hadoke, P. W., Denby, L., Bradshaw, A. C., Caruso, P., Morrell, N. W., Kovacic, J. C., Ulitsky, I., Henderson, N. C., Caporali, A., Leisegang, M. S., Brandes, R. P., Baker, A. H. 2021


    Rationale: Endothelial-to-mesenchymal transition (EndMT) is a dynamic biological process involved in pathological vascular remodelling. However, the molecular mechanisms that govern this transition remain largely unknown, including the contribution of long non-coding RNAs (lncRNAs). Objective: To investigate the role of lncRNAs in EndMT and their relevance to vascular remodelling. Methods and Results: To study EndMT in vitro, primary endothelial cells (EC) were treated with transforming growth factor-beta2 and interleukin-1beta. Single-cell and bulk RNA-sequencing were performed to investigate the transcriptional architecture of EndMT and identify regulated lncRNAs. The functional contribution of seven lncRNAs during EndMT was investigated based on a DsiRNA screening assay. The loss of lncRNA MIR503HG was identified as a common signature across multiple human EC types undergoing EndMT in vitro. MIR503HG depletion induced a spontaneous EndMT phenotype, while its overexpression repressed hallmark EndMT changes, regulating 29% of its transcriptome signature. Importantly, the phenotypic changes induced by MIR503HG were independent of miR-424 and miR-503, which overlap the lncRNA locus. The pathological relevance of MIR503HG down-regulation was confirmed in vivo using Sugen/Hypoxia (SuHx)-induced pulmonary hypertension (PH) in mouse, as well as in human clinical samples, in lung sections and blood outgrowth endothelial cells (BOECs) from pulmonary arterial hypertension (PAH) patients. Overexpression of human MIR503HG in SuHx mice led to reduced mesenchymal marker expression, suggesting MIR503HG therapeutic potential. We also revealed that MIR503HG interacts with the Polypyrimidine Tract Binding Protein 1 (PTB1) and regulates its protein level. PTBP1 regulation of EndMT markers suggests that the role of MIR503HG in EndMT might be mediated in part by PTBP1. Conclusions: This study reports a novel lncRNA transcriptional profile associated with EndMT and reveals the crucial role of the loss of MIR503HG in EndMT and its relevance to pulmonary hypertension.

    View details for DOI 10.1161/CIRCRESAHA.120.318124

    View details for PubMedID 33703914

  • Endothelial function and dysfunction in the cardiovascular system: the long non-coding road CARDIOVASCULAR RESEARCH Monteiro, J. P., Bennett, M., Rodor, J., Caudrillier, A., Ulitsky, I., Baker, A. H. 2019; 115 (12): 1692-1704


    Present throughout the vasculature, endothelial cells (ECs) are essential for blood vessel function and play a central role in the pathogenesis of diverse cardiovascular diseases. Understanding the intricate molecular determinants governing endothelial function and dysfunction is essential to develop novel clinical breakthroughs and improve knowledge. An increasing body of evidence demonstrates that long non-coding RNAs (lncRNAs) are active regulators of the endothelial transcriptome and function, providing emerging insights into core questions surrounding EC contributions to pathology, and perhaps the emergence of novel therapeutic opportunities. In this review, we discuss this class of non-coding transcripts and their role in endothelial biology during cardiovascular development, homeostasis, and disease, highlighting challenges during discovery and characterization and how these have been overcome to date. We further discuss the translational therapeutic implications and the challenges within the field, highlighting lncRNA that support endothelial phenotypes prevalent in cardiovascular disease.

    View details for DOI 10.1093/cvr/cvz154

    View details for Web of Science ID 000491246600010

    View details for PubMedID 31214683

    View details for PubMedCentralID PMC6755355

  • Loss of the Long Non-Coding RNA MIR503HG Promotes Endothelial-to-Mesenchymal Transition Caudrillier, A., Monteiro, J., Rodor, J., Shmakova, A., Baker, A. H. KARGER. 2019: 100-101