Research in the Vascular / Neurobiology Research Area is divided into three research streams aiming at understanding the underlying mechanisms of healthy and pathological nervous system function. The first research stream is focused on vascular physiology and mechanisms of disease in large vessels and capillaries (e.g. arterial hardening, diabetic retinopathy, stroke). Moreover, research is aiming to define the molecular mechanisms for chronic itch and pain, and develop novel analgesics and antipruritics. Lastly, research is focused on understanding the contribution of specialised glia cells called astrocytes to the pathophysiology of neurological and neuropsychiatric diseases and on developing novel gene-therapeutic interventions that target these cells.
Dr. Heller’s current research interests are focused on manipulating astrocyte control of waste clearing in the brain. Specifically, Dr. Heller’s laboratory combines molecular and biochemical approaches together with state-of-the-art super-resolution microscopy imaging to understand how specialised glia cells called astrocytes change in disease and how these cells can be targeted as novel therapeutic intervention to treat neurological and neuropsychiatric diseases.
- Michaluk P, Heller J and Rusakov DA (2021) Rapid recycling of glutamate transporters on the astroglial surface. eLife 10:e64714. DOI: 10.7554/eLife.64714
- Campbell A, Morris G, Heller JP, Langa E, Brindley E, Worm J, Jensen MA, Miller MT, Henshall DC and Reschke CR (2021) Antagomir-mediated suppression of microRNA-134 reduces kainic acid-induced seizures in immature mice. Sci Rep 11(340):1-12. DOI:10.1038/s41598-020-79350-7
- Henneberger C, Bard L, Panatier A, Reynolds JP, Kopach O, Medvedev NI, Minge D, Herde MK, Anders S, Kraev I, Heller JP, Rama S, Zheng K, Jensen TP, Sanchez-Romero I, Jackson CJ, Janovjak H, Ottersen OP and Rusakov DA (2020) LTP induction boosts glutamate spillover by driving withdrawal of astroglia. Neuron 108:1-18. DOI:10.1016/j.neuron.2020.08.030
- Venø MT, Reschke CR, Morris G, Connolly NMC, Su J, Yan Y, Engel T, Jimenez-Mateos EM, Harder LM, Pultz D, Haunsberger SJ, Pal A, Heller JP, Campbell A, Langa E, Brennan GP, Conboy K, Richardson A, Norwood BA, Costard LS, Neubert V, Del Gallo F, Salvetti B, Vangoor VR, Sanz-Rodriguez A, Muilu J, Fabene PF, Pasterkamp RJ, Prehn JHM, Schorge S, Andersen JS, Rosenow F, Bauer S, Kjems J, and Henshall DC (2020) A systems approach delivers a functional microRNA catalog and expanded targets for seizure suppression in temporal lobe epilepsy. Proc Natl Acad Sci USA 117(27). DOI:10.1073/pnas.1919313117
- Heller JP, Odii T, Zheng K and Rusakov DA (2020) Imaging tripartite synapses using super-resolution microscopy. Methods 174:81-90. DOI:10.1016/j.ymeth.2019.05.024
Research Group Members
Natalija Aleksejenko (PhD-track)
(co-supervised with Prof Phil Cummins)
MicroRNA control of astrocytes at the blood-brain-barrier
Funded by a School of Biotechnology PhD Scholarship
The Endothelial Biology Group specializes in fundamental and translational research into vascular cell physiology, signaling (including mechano-signaling), and dysfunction. Particular interests concern the development and interrogation of 2D/3D cellular models of the blood-brain & blood-retinal barriers to assess the underlying mechanisms of disease (e.g. stroke, traumatic brain injury, and vascular complications of diabetes such as diabetic retinopathy and vascular calcification), as well as the impact of novel therapeutics (e.g. COMP-Ang1).
- Harper E, Rochfort KD, Smith D, Cummins PM. RANKL treatment of vascular endothelial cells leading to paracrine pro-calcific signaling involves ROS production. Molecular and Cellular Biochemistry 2020;464:111-117. (PMID: 31724123, DOI: 10.1007/s11010-019-03653-1)
- Rochfort KD, Carroll L, Barabas P, Curtis TM, Ambati BK, Barron N, Cummins PM. COMP-Ang1 stabilizes hyperglycemic disruption of blood-retinal barrier phenotype in human retinal microvascular endothelial cells. Investigative Opthalmology & Visual Sciences 2019;60:3547-3555. (PMID: 31415078, DOI: 10.1167/iovs.19-27644)
- Carroll L, Uehara H, Feng D, Choi S, Singh M, Sandhu Z, Cummins PM, Curtis T, Stitt A, Archer B, Ambati B. Intravitreal AAV2.COMP-Ang1 attenuates deep capillary plexus expansion in the aged diabetic mouse retina. Investigative in Opthalmology & Visual Sciences 2019;60:2494-2502. (PMID: 31185088, DOI: 10.1167/iovs.18-26182)
- Harper E, Rochfort KD, Forde H, Davenport C, Smith D, Cummins PM. Activation of the non-canonical NF-kB/p52 pathway in vascular endothelial cells by RANKL elicits pro-calcific signalling in co-cultured smooth muscle cells. Cellular Signalling 2018;47:142-150. (PMID: 29678621, DOI: 10.1016/j.cellsig.2018.04.004)
- Davenport C, Harper E, Rochfort KD, Forde H, Smith D, Cummins PM. RANKL inhibits the production of OPG from smooth muscle cells under basal conditions and following exposure to cyclic strain. Journal of Vascular Research 2018;55:111-123. (PMID: 29635231, DOI: 10.1159/000486787)
Research Group Members
Funder: DCU/FSH PhD Programme
PhD Project: ‘Super-resolution imaging to uncover microRNA control of astrocytes at the blood-brain-barrier’ This project is investigating the miRNA-based mechanisms that mediate paracrine signalling (e.g. via exosomal exchange) between astrocyte and microvascular endothelial cells comprising the blood-brain barrier in order to understand how they may be altered during epileptic injury to the brain.
Dr. Jianghui Meng is a PI in Molecular Neuroscience and Neurotherapeutics in the National Institute of Cellular Biotechnology. She is funded by SFI and Sanofi Innovation on the translational neuroscience and dermatology. Dr. Meng’s current research interests are focused on defining the itch and pain signaling pathways, elucidating neuroimmune modulation of chronic itch and pain, and developing novel analgesics and antipruritics. These therapeutics have advantages being effective and cost-efficient, with abilities to change patients’ life in a meaningful way. Dr. Meng has established several novel concepts for itch and pain management and identified novel therapeutic interventions, which formed the new basis for the accomplishment of transformational “mechanism-based” high-quality treatments.
- Larkin, C., Chen, W., Szabó, I.L., Shan, C., Dajnoki, Z., Szegedi, A., Buhl, T., Fan, Y., O’Neill, S., Walls, D., Cheng, W., Xiao, S., Wang, J., Meng, J. Novel insights into the TRPV3-mediated itch in atopic dermatitis. (2021) Journal of Allergy and Clinical Immunology, 147 (3), pp. 1110-1114.e5. https://pubmed.ncbi.nlm.nih.gov/33035568/. DOI: 10.1016/j.jaci.2020.09.028.
- Meng, J., Chen, W., Wang, J. Interventions in the B-type natriuretic peptide signalling pathway as a means of controlling chronic itch. (2020) British Journal of Pharmacology, 177 (5), pp. 1025-1040. https://pubmed.ncbi.nlm.nih.gov/31877230/. DOI: 10.1111/bph.14952.
- Meng, J., Wang, J., Buddenkotte, J., Buhl, T., Steinhoff, M. Role of SNAREs in Atopic Dermatitis–Related Cytokine Secretion and Skin-Nerve Communication. (2019) Journal of Investigative Dermatology, 139 (11), pp. 2324-2333. https://pubmed.ncbi.nlm.nih.gov/31128202/. DOI: 10.1016/j.jid.2019.04.017.
- Meng, J., Moriyama, M., Feld, M., Buddenkotte, J., Buhl, T., Szöllösi, A., Zhang, J., Miller, P., Ghetti, A., Fischer, M., Reeh, P.W., Shan, C., Wang, J., Steinhoff, M. New mechanism underlying IL-31–induced atopic dermatitis. (2018) Journal of Allergy and Clinical Immunology, 141 (5), pp. 1677-1689.e8. https://pubmed.ncbi.nlm.nih.gov/29427643/. DOI: 10.1016/j.jaci.2017.12.1002.
- Meng, J., Wang, J. Role of SNARE proteins in tumourigenesis and their potential as targets for novel anti-cancer therapeutics. (2015) Biochimica et Biophysica Acta – Reviews on Cancer, 1856 (1), pp. 1-12. https://pubmed.ncbi.nlm.nih.gov/25956199/ . DOI: 10.1016/j.bbcan.2015.04.002.