Department: Comparative Biomedical Sciences
Research Groups: Cardiovascular and Renal Biology
Jennifer is a postdoctoral researcher working with Dr. Caroline Pellet-Many to investigate the mechanisms regulating vascular smooth muscle cell (VSMC) behaviour associated with cardiovascular disease. Using in vitro and in vivo models, Jennifer explores the role of a family of cell surface proteins in the VSMC response to inflammation.
Jennifer completed a BSc in Bioveterinary Science at the RVC before moving onto the University of Cambridge. At the University of Cambridge, Jennifer worked as a research assistant with Dr Helle Jørgensen, investigating vascular smooth muscle cell (VSMC) plasticity in the healthy and diseased vasculature. While a research assistant, Jennifer worked on a project exploring the epigenetic mechanisms underlying VSMC plasticity, which became the basis of her PhD. After completing her PhD, Jennifer joined the RVC to work with Dr Caroline Pellet-Many as a postdoctoral researcher. Jennifer studies the role of Neuropilins, a family of cell surface proteins, in the regulation of VSMC behaviour associated with cardiovascular disease.
Jennifer is an RVC Researcher Association committee member. Jennifer helps represent contract researchers on various committees, promotes career development opportunities and maintains the association’s social media accounts.
Vascular smooth muscle cells (VSMCs) are the main cellular component of large to medium-sized blood vessels, which contract to regulate blood flow within the vasculature. However, recent cell lineage tracing studies have demonstrated that VSMCs can alter their behaviour in response to numerous environmental cues, and directly contribute to the initiation and progression of atherosclerosis. Atherosclerosis describes the build-up of cells (plaque) inside the blood vessel wall. Importantly, recent genetic lineage tracing studies have unequivocally shown that 40-90% of plaque resident cells are derived from healthy "contractile" VSMCs. Almost all people have atherosclerosis to some extent. The development of atherosclerotic plaque begins in childhood and worsens with age. Later in life, atherosclerosis can obstruct blood flow to vital organs and lead to catastrophic clinical complications, including heart attack and stroke.
In response to injury and/or inflammation, VSMCs produce high levels of Neuropilins, a family of proteins found at the cell surface. Neuropilins are known to control various signals which tell cells to alter their behaviour in response to local environmental signals. Using in vitro and in vivo models, Jennifer explores the role of Neuropilins in the regulation of VSMC behaviour associated with cardiovascular disease, including the VSMC response to inflammation, immune cell recruitment and lipid retention within the vasculature.
Worssam MD, Lambert J, Oc S, Taylor AL, Dobnikar L, Chappell J, et al. Primed smooth muscle cells acting as first responder cells in disease. bioRxiv. 2020: p. 2020.10.19.345769.
Harman, J.L., et al., Emerging Roles for Neuropilin-2 in Cardiovascular Disease. Int J Mol Sci, 2020. 21(14).
Harman, J.L. and H.F. Jørgensen, The role of smooth muscle cells in plaque stability: Therapeutic targeting potential. Br J Pharmacol, 2019. 176(19): p. 3741-3753.
Harman, J.L., et al., Epigenetic Regulation of Vascular Smooth Muscle Cells by Histone H3 Lysine 9 Dimethylation Attenuates Target Gene-Induction by Inflammatory Signaling. Arterioscler Thromb Vasc Biol, 2019. 39(11): p. 2289-2302.
Dobnikar, L., et al., Disease-relevant transcriptional signatures identified in individual smooth muscle cells from healthy mouse vessels. Nat Commun, 2018. 9(1): p. 4567.
Tomaz, R.A., Harman, J.L., et al., Jmjd2c facilitates the assembly of essential enhancer-protein complexes at the onset of embryonic stem cell differentiation. Development, 2017. 144(4): p. 567-579.
Chappell, J., Harman, J.L., et al., Extensive Proliferation of a Subset of Differentiated, yet Plastic, Medial Vascular Smooth Muscle Cells Contributes to Neointimal Formation in Mouse Injury and Atherosclerosis Models. Circ Res, 2016. 119(12): p. 1313-1323.
Jennifer has experience in designing and supervising final year BSc student laboratory projects. Jennifer can help teach the methods and principles behind numerous laboratory techniques, including cell culture, RNA extraction, mRNA-seq, RT-qPCR, western blotting, FACS analysis, siRNA transfection, preparing expression plasmids for viral transduction, chromatin immunoprecipitation (ChIP), immunofluorescent staining, confocal imaging and in vivo models of vascular disease.