Dr Lin-Hua Jiang

Profile

I started independent research in 2004 as a University Research Fellow in the School of Biomedical Sciences at University of Leeds in the UK, supported by a prestigious 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. In addiiton, I am a visiting Professor at University of Tours in France.

I completed BSc in Physics (1982-1987) and MSc in Biophysics (1987-1990) and held a lecturership position (1990-1995) in the Department of Physics at East China Normal University in China. I obtained PhD in Pharmacology (1995-1999) under the supervision of Prof D Wray in the School of Biomedical Sciences at University of Leeds, and carried out postdoctoral training (1999-2003) with Prof RA North, FRS, in the Department of Biomedical Science at University of Sheffield in the UK.

 

Research interests

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 specific ion channel inhibitors as novel research tools and therapeutics, foucsing on the areas described below. So far, I have contributed 76 original research and review articles published by Science Citation Index (SCI) journals.

TRPM2 channel and ROS signalling in neurodegeneration

The transient receptor potential melastatin-related 2 (TRPM2) channel is gated by cytosolic ADP-ribose. Our studies have contributed in 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.

TRPM2 channels are strongly activated in response to elevated levels of ROS and thus act as a molecular sensor for oxidative stress under diverse pathophysiological settings (Jiang et al., 2010; Li et al., 2015; Syed Mortadza et al., 2015). TRPM2 channels have been shown to be important in mediating ROS-induced cell death (Zhou et al., 2013; Manna et al., 2015; Yu et al., 2015; Syed Mortadza et al., 2017; Li et al., 2017; Li and Jiang, 2018).  We are currently investigating the TRPM2 mechanisms underpinning brain diseases such as ischemic stroke, Alzheimer's, Parkinson's, Huntington's, Multiple Sclerosis and Amyotropic Lateral Sclerosis (Ye et al., 2014; Li and Jiang, 2018; Syed Mortadza et al., 2018; Jiang et al., 2018).

TRPM2 specific inhibitor or antagonist is still lacking. We are working along with collaborators in developing TRPM2 channel inhibitors as research tools and therapeutics and, in combining molecular biology, structural biology and electrophysiology, understand the molecular mechanisms of their actions.

P2X7 receptor and ATP signalling in inflammatory diseases and cancers

The P2X7 receptor, while belonging to the ATP-gated ion 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, ion channel gating and large pore formation (Bradley et al., 2010, 2011; Caseley et al., 2015; 2017), using site-directed mutagenesis and electrophysiology in combination with cryo-EM and structural modelling.

P2X7 receptors play a critical role in immune responses. Change in the P2X7 receptor expression and/or function has been causatively associated with diverse inflammatory diseases (Jiang et al., 2013; Caseley et al., 2014; Roger et al., 2015; Wei et al., 2018).  The gene encoding the human P2X7 receptor is prolific with non-synonymous single nucleotide polymorphisms (NS-SNP); expression of such gain/loss-of-functional NS-SNPs alters the susceptibility of individuals to various disease conditions. We are investigating the effects of NS-SNP mutations on receptor functions in order to gain insights into the disease mechanisms (Roger et al., 2011; Bradley et al., 2011).

We were the first to report brilliant blue G (BBG) as a P2X7 antagonist (Jiang et al., 2000), which has been widely-used as a research tool that unravels many previously unknown functions for the P2X7 receptor in physiology and pathologies. Our collaborative research has identified emodin, a natural compound, as a P2X7 antagonist and showed that it was effective in inhibiting P2X7-mediated cancer cell metastasis (Liu et al., 2010; Jelassi et al., 2013). Recently, we have reported identification of the  novel P2X7 antagonists using a structure-based approach (Caseley et al., 2016).

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  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 recent publications [IF: journal impact factor published by Clarivate Analytics in 2017; *: senior author(s)]

  • 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)
  • 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.* (2018) A critical role of the TRPM2 channel in a positive feedback mechanism for ROS-induced delayed cell death. Journal of Cellular Physiology (in press) (IF3.923)

Research projects

We can offer the following research projects for PhD and Master by Research studies. Please email to: l.h.jiang@leeds.ac.uk if you are interested in joining us for your postgraduate study.

  • TRPM2 channel signalling mechanisms in neuronal death related to ischemic stroke and neurodegenerative diseases
  • TRPM2 channel signalling mechanisms in neuroinflammation related to 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 mechnaisms in neuroninflammation related to neurodegenerative and psychiatric diseases
  • Struture 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

Lab alumni

  • 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
<h4>Research projects</h4> <p>Any research projects I'm currently working on will be listed below. Our list of all <a href="https://biologicalsciences.leeds.ac.uk/dir/research-projects">research projects</a> allows you to view and search the full list of projects in the faculty.</p>

Student education

Faculty Graduate School

FindaPhD Project details:

<h4>Postgraduate research opportunities</h4> <p>We welcome enquiries from motivated and qualified applicants from all around the world who are interested in PhD study. Our <a href="https://biologicalsciences.leeds.ac.uk/research-opportunities">research opportunities</a> allow you to search for projects and scholarships.</p>