Dr Lin-Hua Jiang
I studied BSc in Physics (1982-1987) and MSc in Biophysics (1987-1990) and held a lectureship position (1990-1995) in the Department of Physics at East China Normal University in China. I completed PhD in Pharmacology (1995-1999) under the supervision of Prof D Wray in the School of Biomedical Sciences at University of Leeds, and received postdoctoral training (1999-2003) from Prof RA North, FRS, in the Department of Biomedical Science at University of Sheffield in the UK.
I started my own research in 2004 as an independent University Research Fellow in the School of Biomedical Sciences at University of Leeds in the UK, supported by a five-year Wellcome Trust University Award (2004-2008). Currently, I am a lecturer in Membrane Biology and a research group leader in the School of Biomedical Sciences, Faculty of Biological Sciences, at University of Leeds. So far, I have contributed 78 original research and review articles with h-index of 28 (Web of Sciences), 29 (Scopus) or 32 (Google Scholar).
Molecular and structural mechanisms of calcium-permeable ion channels in health and disease
The overall aim of the research in my laboratory is to elucidate the molecular and structural mechanisms of calcium-permeable channels in health and disease and to develop novel inhibitors as research tools and therapeutics, focusing on the following areas.
TRPM2 channel and ROS signalling in ageing and age-related neurodegenerative diseases
The transient receptor potential melastatin-related 2 (TRPM2) channel is gated by cytosolic ADP-ribose. Our studies contribute in better understanding the molecular basis determining the channel assembly, ion permeation, ligand binding and functional regulation (Mei et al., 2006; Xia et al., 2008; Yang et al., 2010, 2011; Zou et al., 2011; Yu et al., 2014, 2017). Currently, we are interested in studying the molecular and structural basis for ligand binding, channel gating and allosteric modulation, using site-directed mutagenesis and electrophysiology in combination with cryo-EM and structural modelling.
The TRPM2 channels are strongly activated in response to elevated levels of ROS and act as a molecular sensor or mediator of oxidative stress, which is a salient characteristic of normal ageing and diverse age-related pathophysiological processes, such as ischemic stroke, Alzheimer's and Parkinson's diseases (Jiang et al., 2010, 2018; Li et al., 2015; Syed Mortadza et al., 2015). The TRPM2 channels have been shown to be important in mediating ROS-induced neurodegeneration and neuroinflammation (Ye et al., 2014; Syed Mortadza et al., 2017; Li et al., 2017; Li and Jiang, 2018). We are currently investigating TRPM2-dependent signalling mechanisms underpinning normal ageing and age-related diseases that lead to a progressive decline or loss of cognitive function (Jiang et al., 2018).
TRPM2-specific inhibitor or antagonist is still lacking. We are interested in developing TRPM2 channel inhibitors as research tools and therapeutics and, in combining molecular biology, structural biology and electrophysiology, understand the mechanisms of actions.
P2X7 receptor and ATP signalling in diseases
The P2X7 receptor, while belonging to the ATP-gated channel P2X receptor family, exhibits unique functional and pharmacological properties (Jiang et al., 2013). We are interested in the structural basis that governs ligand binding, channel gating, and ion permeation (Bradley et al., 2010, 2011; Caseley et al., 2015, 2017), using site-directed mutagenesis and electrophysiology in combination with cryo-EM and structural modelling.
Activation of the P2X7 receptors requires high levels of extracellular ATP, which is associated with tissue damage and inflammation and also a feature of cancer microenvironments. The P2X7 receptors play a critical role in normal immune responses, and change in the P2X7 receptor expression and/or function increase the susceptibility to various conditions such as breast cancer, age-dependent macular degeneration, anxiety and depression (Jelassi et al., 2013; Jiang et al., 2013; Caseley et al., 2014; Roger et al., 2015; Wei et al., 2018). We are interested in P2X7-dependent signalling mechanisms in the pathogenesis and progression of these diseases.
We were the first to report brilliant blue G as a P2X7 antagonist (Jiang et al., 2000), which has been widely-used as a research tool to unravel many previously unknown physiological and pathological functions of the P2X7 receptors. Our collaborative research has identified emodin, a natural compound, as a P2X7 antagonist and show that it is effective in inhibiting P2X7-mediated cancer cell metastasis (Liu et al., 2010; Jelassi et al., 2013). With increasing availability of structural information, we are interested in structure-guided approaches used to develop novel P2X7 antagonists (Caseley et al., 2016), particularly brain-penetrable antagonits (Jiang et al., 2018).
ATP-induced calcium signalling in mesenchymal stem cell functions
Mesenchymal stem cells (MSCs) exhibit a capacity of osteogenesis, adipogenesis, chondrogenesis and possible differentiation along other lineages, and hold great promise in cell-based therapies and tissue regeneration. The extrinsic and intrinsic signals and associated signalling mechanisms that control or regulate MSC proliferation, migration and differentiation are still poorly understood. We are interested in identifying the extrinsic signalling molecules and related intrinsic mechanisms in MSCs. Our recent study shows that purinergic and store-operated calcium signalling mechanisms play an important role in ATP-induced stimulation of MSC migration (Peng et al., 2016; Jiang et al., 2017). We are also interested in exploring the translational potential of manipulating such signalling mechanisms in tissue engineering.
Our researches have been supported by (1) grants from BBSRC, Wellcome Trust, Royal Society, and Alzheimer Research Trust; (2) scholarships to talented postgraduate students from BBSRC, EPSRC, Wellcome Trust, University of Leeds, Chinese Scholar Council (CSC) and other governmental agencies; and (3) productive collaborations with scientists in diverse disciplines in and outside Leeds.
Representative publications in recent 5 years [ *: senior author(s); IF: journal impact factor published by Clarivate Analytics in 2018]
- Ye, M., Yang, W.*, Ainscough, J. F., Hu, X., Sedo, A., Zhang, X., Zhang, X., Chen, Z., Li, X., Beech, D. J., Sivaprasadarao, A., Luo, J.* and Jiang, L.-H.* (2014) TRPM2 channel deficiency prevents delayed cytosolic Zn2+ accumulation and CA1 pyramidal neuronal death after transient global ischemia. Cell Death & Disease 5: e1541 (IF5.638)
- Zhang, Q.Y., Zhang, Y.Y., Xie, J., Li, C.X., Chen, W.Y., Liu, B.L., Wu, X.A., Li, S.N., Huo, B., Jiang, L.-H.* and Zhao, H.C.* (2014) Stiff substrates enhance cultured neuronal network activity. Scientific Reports 4: 6215 (IF4.122)
- Syed Mortadza, S.A., Wang, L., Li, D.-L. and Jiang, L.-H.* (2015) TRPM2 channel-mediated ROS-sensitive Ca2+ signaling mechanisms in immune cells. Frontiers in Immunology 6: 407 (IF5.511)
- Li, C.-K., Meng, L., Li, X., Li D.-L. and Jiang, L.-H.* (2015) Non-NMDAR neuronal Ca2+-permeable channels in transient ischemia-induced neuronal death as therapeutic targets for ischemic stroke. Expert Opinion on Therapeutic Targets 19: 879-892 (IF4.789)
- Peng, H.S., Hao, Y.J., Mousawi,F., Roger, S., Li, J., Sim, J. A., Ponnambalam, S., Yang, X.B. and Jiang, L.-H.* (2016) Purinergic and store-operated Ca2+ signalling mechanisms in mesenchymal stem cells and their roles in ATP-induced stimulation of cell migration. Stem Cells 34: 2102-2114 (IF5.587)
- Xu, F., Wu, X., Jiang, L.-H., Zhao, H. and Pan, J. (2016) An organelle K+ channel is required for osmoregulation in Chlamydomonas reinhardtii. Journal of Cell Science 129: 3008-3014 (IF4.401)
- Caseley, E.A., Muench, S.P., Fishwick, C.W. and Jiang, L.-H.* (2016) Structure-based identification and characterisation of structurally novel human P2X7 receptor antagonists. Biochemical Pharmacology 116: 130-139 (IF4.235)
- Syed Mortadza, S.A., Sim, J.A., Stacey, M. and Jiang, L.-H.* (2017) Signalling mechanisms mediating Zn2+-induced TRPM2 channel activation and death cell in microglial cells. Scientific Reports 7: 45032 (IF4.122)
- Zhao, H., Yu, Y., Wu, X., Liu, S., Liu, B., Du, J., Li, B., Jiang, L.-H.* and Feng, X.* (2017) A role of BK channel in regulation of Ca2+ channel in ventricular myocytes by substrate stiffness. Biophysical Journal 112: 1406-1416 (IF3.495)
- Jiang, L.-H.*, Mousawi, F., Yang, X.B. and Roger, S. (2017) ATP-induced Ca2+-signalling mechanisms in the regulation of mesenchymal stem cell migration. Cellular and Molecular Life Sciences 74: 3697-3710 (IF6.721)
- Abuarab, N., Munsey, T.S., Jiang, L.-H., Li, J. and Sivaprasadarao, A. (2017) High glucose-induced ROS activates TRPM2 to trigger lysosomal membrane permeabilization and Zn2+-mediated mitochondrial fission. Science Signalling 10: 4161 (IF6.378)
- Jiang, Q., Gao, Y., Wang, C., Liao, M., Wu, Y., Zhan, K., Lu, N., Tao, R., Lu, Y., Wilcox, C.S., Luo, J., Jiang, L.-H.*, Yang, W.* and Han, F.* (2017) Nitration of TRPM2 as a molecular switch induces autophagy during brain pericyte injury. Antioxidants and Redox Signaling 27: 1297-1316 (IF6.53)
- Li, X., Yang, W. and Jiang, L.-H.* (2017) Alteration in intracellular Zn2+ homeostasis as a result of TRPM2 channel activation contributes to ROS-induced hippocampal neuronal death. Frontiers in Molecular Neuroscience 10: 144 (IF3.902)
- Syed Mortadza, S.A., Sim, J.A., Neubrand, V. E. and Jiang, L.-H.* (2018) A critical role of TRPM2 channel in Aβ42-induced microglial activation and generation of tumour necrosis factor-α. Glia 66: 562-575 (IF5.846)
- Li, X. and Jiang, L.-H.* (2018) Multiple molecular mechanisms form a positive feedback loop driving amyloid β42 peptide-induced neurotoxicity via activation of the TRPM2 channel in hippocampal neurons. Cell Death & Disease 9: 195 (IF5.638)
- Wei, L., Syed Mortadza, S.A., Yan, J., Zhang, L., Wang, L., Yin, Y., Li, C., Chalon, S., Emond, P., Belzung, C., Li, D., Lu, C., Roger, R. and Jiang, L.-H.* (2018) ATP-activated P2X7 receptor in the pathophysiology of mood disorders and as an emerging target for the development of novel antidepressant therapeutics. Neuroscience & Biobehavioral Reviews 87: 192-205 (IF8.037)
- Jiang, L.-H.*, Li, X., Syed Mortadza, S.A., Lovatt, M. and Yang, W. (2018) The TRPM2 channel nexus from oxidative damage to Alzheimer’s pathologies: an emerging novel intervention target for age-related dementia. Aging Research Review 47: 67-79 (IF8.973)
- Li, X. and Jiang, L.-H.* (2019) A critical role of the TRPM2 channel in a positive feedback mechanism for ROS-induced delayed cell death. Journal of Cellular Physiology 234: 3647-3660 (IF3.923)
We can offer the following research projects for PhD and Master by Research studies. Please email to: email@example.com if you are interested in joining us for your postgraduate study.
- TRPM2 channel signalling mechanisms in neurodegeneration related to ageing, ischemic stroke and neurodegenerative diseases
- TRPM2 channel signalling mechanisms in neuroinflammation contributing to ageing, age-related neurodegenerative and psychiatric diseases
- Regulation of TRPM2 channel expression and trafficking by interacting proteins
- Structural basis of TRPM2 channel gating and interactions with ligands
- Development of TRPM2 channel inhibitors and invesigation of the mechanisms of actions
- P2X7 receptor signalling mechanisms in neuroinflammation contributing to ageing, age-related neurodegenerative and psychiatric diseases
- Structural basis of P2X7 receptor activation and interactions with ligands
- Structure-guided design of P2X7 receptor inhibitors and investigation of the mechanisms of actions
- ATP-induced signalling mechanisms in stem cell functions
- ATP-induced signalling mechanisms in cancer cell functions
- Mechanical stimuli-induced signalling mechanisms in stem cell functions
- Mechanical stimuli-induced signalling mechanisms in cancer cell functions
- Ionic signalling mechanisms underlying brain cell-substrate interaction
- Development of novel 2D and 3D cell-supporting substrates or scaffolds for neuronal tissue engineering
- Zhuzhong Mei (2004-2007), Research fellow
- Rong Xia (2005-2009), PhD student; a recipient of Chinese Government Award for Outstanding Self-Financed Student Studying Abroad in 2008
- Hongju Mao (2005-2006), Research fellow
- Xing Liu (2006-2009), Research fellow
- Helen J Bradley (2006-2010), PhD student
- Wei Yang (2009-2011), Research fellow
- Jie Zou (2009-2013), PhD student
- Hongsen Peng (2010-2014), PhD student
- Yunjie Hao (2014-2015), MSc by Research student
- Emily A Caseley (2013-2016), PhD student
- Xin Li (2013-2017), PhD student
- Sharifah Alawieyah Syed Mortadza (2013-2017), PhD student
Current lab members
- Fatema Mousawi, PhD student
- John Brewster, PhD student
- Philippa Malko, PhD student
- Harneet Mankoo, MSc by Research student
- Megan Lovatt, MBiol student
- Joseph McWilliam, Laidlaw project student
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