Zhiliang Lv


Qualifications

Ph.D.   Shanghai Jiaotong University,  Shanghai, China,  Medicine,  1990

M.Sc.   Zhejiang University,  Hangzhou, China,  Medicine,  1987

B.Sc.   Zhejiang University,  Hangzhou, China,  Medicine,  1984


Experience

Professor, Department of Biological Sciences at XJTLU (September, 2013 - Present), Suzhou, China-PRC.

Associate Professor, Department of Biological Sciences at XJTLU (April, 2011 - August, 2013), Suzhou, China-PRC.

Tenured Programme Leader, MRC Human Reproductive Sciences Unit at Edinburgh University, Medical Research Council UK (March, 2007 - March, 2011), Edinburgh, United Kingdom.

Programme Leader Track, MRC Human Reproductive Sciences Unit at Edinburgh University, Medical Research Council UK (October, 2001 - March, 2007), London, United Kingdom.

Senior Scientist (Band 3), Department of Physical Biochemistry, National Institute for Medical Research, Mill Hill, London, Medical Research Council UK (May, 1997 - September, 2001), London, United Kingdom.

Associate Professor, Department of Biological Sciences and Technology, Zhejiang University (December, 1992 - April, 1999), Hangzhou, China-PRC.

Wellcome Trust Overseas Travelling Fellowship, Department of Physical Biochemistry, National Institute for Medical Research, Medical Research Council UK (May, 1995 - April, 1997), London, United Kingdom.

Lecturer, Department of Biological Sciences and Technology, Zhejiang University (January, 1991 - December, 1992), Hangzhou, China-PRC.


Professional Memberships 

American Endocrine Society, 2008, 2008

Editorial Member of Neuroendocrinology, 2006-2016, 2006-2016

Biochemical Society, 1997, 1997


Honors and Awards 

2011:  Jinji Lake 200 Talent Programme, Suzhou Industrial Park.

1994:  Excellent Young Teacher, Zhejiang University.

1993:  Yilida Excellent Teacher, Zhejiang University.  one of the highest awards.

1993:  Supervisor of PhD students, Zhejiang University.

1992:  Excellent paper, The Science and Technology Association of Zhejiang Province.

1992:  Award of Science & Technology, Zhejiang University.


Research Interests 

Research Interests

Our research focuses mainly on elucidation of how neuropeptides binds to their cognate 7TM G protein-coupled receptors (GPCRs) at the extracellular side of the cell membrane and understanding how the peptide binding induces receptor conformational changes. These changes lead to association and activation of signalling molecules at the intracellular side of the cell membrane which then trigger diverse downstream signalling cascades, resulting in changes in cellular functions.

We use molecular modelling and ligand docking to generate hypotheses of ligand-receptor interactions and receptor intra-molecular interactions involved in the receptor conformational switch. These will be tested by mutagenesis, biochemical and biophysical studies. We endeavour to identify the structural determinants of peptide analogues and their cognate GPCRs which selectively stabilise/induce different receptor active conformations preferentially activating distinctive signalling pathways/cellular functions (ligand-induced selective signalling/functional selectivity). These studies will assist in the development of signal-selective ligands/drugs directed at different clinical endpoints with improved therapeutic outcomes and reduced side-effects.

When activated, GPCRs can couple to different G proteins in addition to its cognate G protein, or other GPCR-interacting proteins to mediate differential biological functions. We are attempting to dissect these interactions at the molecular level, to unravel the mechanisms of neuropeptides in modulation of multiple pathophysiological functions such as hormone secretion and cancer cell metastasis, and to develop therapeutic peptides targeted against protein-protein interaction (PPI).


Publications 

Gordienko, D., Povstyan, O., Sukhanova, K., Raphael, M., Harhun, M., Dyskina Y, Lehen'kyi V, Jama A, Lu ZL, Skryma R, Prevarskaya N (2015).  Impaired P2X-signaling pathways in renal microvascular myocytes in genetic hypertension.   Cardiovascular Research, 105, 131-142.


Meng, J., Lu, Z., Liu, H., Zhang, L., Zhang, S., Chen Y, Rao MK and Huang Y (2014).  A protocol for RNA methylation differential analysis with MeRIP-Seq.   Methods, 69, 274-281, doi: http://dx.doi.org/10.1016/j.ymeth.2014.06.008.


Book, M., McCracken, L., Reddington, J., Lv, Z., Morrice, N., Gray NK (2012).  Extensive dynamic post-translational modification of the multifunctional poly(A)-binding protein 1 may coordinate its activities.   Biochem, 441, 803-812.


Forfar, R. & Lv, Z. (2011).  Role of transmembrane domain 4/extracellular loop 2 junction of the human gonadotropin-releasing hormone receptor in ligand binding and receptor conformational selection.   J Biol Chem, 286 (40), 34617-34626.


Kaye, R., Saldanha, J., Lv, Z., & Hulme, E. (2011).  Helix 8 of the M1 muscarinic acetylcholine receptor: scanning mutagenesis delineates a G protein recognition site.   Mol Pharmacol (79), 701-709.


White, C., Stewart, A., Lv, Z., Millar, R., & Morgan, K. (2008).  Anti-proliferative effects of GnRH agonists: prospects and problems for cancer therapy.   Neuroendocrinology (88), 67-79.


Stewart, A., Sellar, R., Wilson, D., Millar, R., & Lv, Z. (2008).  Identification of a novel ligand binding residue Arg38(1.35) in the human gonadotropin-releasing hormone receptor.   Mol Pharmacol (73), 75-81.


Coetsee, M., Millar, R., Flanagan, C., & Lv, Z. (2008).  Identification of Tyr(290(6.58)) of the human gonadotropin-releasing hormone (GnRH) receptor as a contact residue for both GnRH I and GnRH II: importance for high-affinity binding and receptor activation.   Biochemistry (47), 10305-10313.


Millar, R., Pawson, A., Morgan, K., & Lv, Z. (2008).  Diversity of actions of GnRHs mediated by ligand-induced selective signalling.   Frontiers in Neuroendocrinology (29), 17-35.


White, C., Coetsee, M., Morgan, K., Flanagan, C., Millar, R., Lu ZL (2008).  A crucial role for Galphaq/11, but not Galphai/o or Galphas, in gonadotropin-releasing hormone receptor-mediated cell growth inhibition.   Mol Endocrinol (22), 2520-2530.


Lopez de Maturana, R., Pawson, A., Lv, Z., Davidson, L., Maudsley, S., Morgan K, Langdon SP, Millar RP (2008).  Gonadotropin-releasing hormone analog structural determinants of selectivity for inhibition of cell growth: support for the concept of ligand-induced selective signalling.   Mol Endocrinol (22), 1711-1722.


Pawson, A., Faccenda, E., Maudsley, S., Lv, Z., Naor, Z., Millar RP (2008).  Mammalian type I gonadotropin-releasing hormone receptors undergo slow, constitutive, agonist-independent internalization.   Endocrinology (149), 1415-1422.


Lv, Z., Coetsee, M., White, C., & Millar, R. (2007).  Structural determinants for ligand-receptor conformational selections in a peptide G protein-coupled receptor.   J Biol Chem (282), 17921-17929.


Mamputha, S., Lv, Z., Roeske, R., Millar, R., Katz, A., Flanagan CA (2007).  Conserved amino acid residues that are important for ligand binding in the Type 1 gonadotropin-releasing hormone (GnRH) receptor are required for high potency of GnRH II at the Type II GnRH receptor.   Mol Endocrinol (21), 281-292.


Topaloglu, A., Lv, Z., Farooqi, I., Mungan, N., Yuksel, B., O'Rahilly S, Millar RP (2006).  Molecular genetic analysis of normosmis hypogonadotropic hypogonadism in a Turkish population: identification and detailed functional characterization of a novel mutation in the gonadotropin-releasing hormone receptor gene.   Neuroendocrinology (84), 301-308.


Morgan, K., Sellar, R., Pawson, A., Lv, Z., & Millar, R. (2006).  Bovine and ovine GnRH-II ligand precursors and Type II GnRH receptor genes are functionally inactivated.   Endocrinology (147), 5041-5051.


Barran, P., Roeske, R., Pawson, A., Sellar, R., Bowers, M., Morgan K, Lu ZL, Tsuda M, Kusakabe T, Millar RP (2005).  Evolution of constrained gonadotropin-releasing hormone ligand conformation and receptor selectivity.   J Biol Chem (280), 38569-38575.


Lv, Z., Gallagher, R., Sellar, R., Coetsee, M., & Millar, R. (2005).  Mutations remote from the human gonadotropin-releasing hormone (GnRH) receptor binding sites specifically increase binding affinity for GnRH II, but not GnRH I: evidence for ligand-selective receptor active conformations.   J Biol Chem (280), 29796-29803.


Millar, R., Lv, Z., Pawson, A., Flanagan, C., Morgan, K., Maudsley SR (2004).  Gonadotropin-releasing hormone receptors.   Endocr Rev (25), 235-275.


Hulme, E., Lv, Z., & Bee, M. (2003).  Scanning mutagenesis studies of the M1 muscarinic acetylcholine receptor.   Receptors and Channels (9), 215-228.


Hulme, E., Lv, Z., Saldanha, J., & Bee, M. (2003).  Structure and activation of muscarinic acetylcholine receptors.   Biochem Soc Trans (31), 29-34.


Zheng, Q., Zheng, Y., & Lv, Z. (2002).  Immunomodulatory effects of the polysaccharides of Cistanche Deserticola Y C Ma.   Zhejiang Da Xue Xue Bao Yi Xue Ban (31), 284-287.


Lv, Z., Saldanha, J., & Hulme, E. (2002).  Seven-transmembrane receptors: crystals clarify.   Trends Pharmacol Sci (23), 140-146.


Lv, Z. & Hulme, E. (2001).  Functional importance of transmembrane domains 4 and 7 of the M1 muscarinic acetylcholine receptor.   Life Sci (68), 2640.


Hulme, E., Lv, Z., Bee, M., Curtis, C., & Saldanha, J. (2001).  The conformational switch in muscarinic acetylcholine receptor.   Life Sci (68), 2495-2500.


Lv, Z., Saldanha, J., & Hulme, E. (2001).  Transmembrane domain 4 and 7 of the M1 muscarinic acetylcholine receptor are critical for ligand binding and the receptor activation switch.   J Biol Chem (276), 34098-34104.


Lv, Z. & Hulme, E. (2000).  A network of conserved intramolecular contacts defines the off-state of the transmembrane switch mechanism in a seven-transmembrane receptor.   J Biol Chem (275), 5682-5686.


Yuan, H. & Lv, Z. (1999).  Stuay of Immunoregulation effect of polysaccharide of glossy privet fruit.   Journal of Chinese Herbal Medicine of China, 24 (11), 691-693.


Hulme, E., Lv, Z., Ward, S., Allman, K., & Curtis, C. (1999).  The conformational switch in 7-transmembrane receptors: the muscarinic receptor paradigm.   Eur J Pharmacol (375), 247-260.


Lv, Z. & Hulme, E. (1999).  The functional topography of transmembrane domain 3 of the M1 muscarinic acetylcholine receptor, revealed by scanning mutagenesis.   J Biol Chem (274), 7309-7315.


Hulme, E. & Lv, Z. (1998).  Scanning mutagenesis of transmembrane domain 3 of the M1 muscarinic acetylcholine receptor.   J Physiol (Paris) (92), 269-274.


Lv, Z. & Hulme, E. (1998).  Alanine scanning mutagenesis of the extracellular half of transmembrane domain 3 of the M1 muscarinic acetylcholine receptor.   Naunyn-Schmiederberg’s Arch Pharmacol (358), 520.


Zheng, Q., Mao, J., & Lv, Z. (1998).  Purification of the polysaccharides of Cistanche Deserticola Y C Ma and its effect on the function of T-lymphocytes.   Zhejiang Yi Ke Da Xue Xue Bao (27), 108-111.


Lv, Z., Jones, P., Curtis, C., & Hulme, E. (1997).  Asp122 and Tyr124 in the M1 muscarinic receptor are critical for receptor folding but not for signalling.   Life Sci (60), 1176.


Lv, Z., Curtis, C., Jones, P., Pavia, J., & Hulme, E. (1997).  The role of the aspartate-arginine-tyrosine triad in the M1 muscarinic receptor: mutations of aspartate 122 and tyrosine 124 decrease receptor expression but do not abolish signalling.   Mol Pharmacol (51), 234-241.


Lv, Z. & Hulme, E. (1997).  Alanine scanning mutagenesis study of transmembrane helix 3 (intracellular half) in the M1 muscarinic receptor.   FASEB J (11), A1331.


Wang, H., Lv, Z., & Zhang, W. (1996).  Roles of the carbohydrate moiety of hCG in the receptor binding and activation.   Zhejiang Da Xue Xue Bao (30), 157-163.


Lv, Z., Wang, H., & Zhang, W. (1996).  Inhibitory effects of glycopeptides on the hCG-stimulated cAMP responses.   Acta Biologiae Experimentalis Sinica (29), 119-123.


Mao, J., Lv, Z., Zheng, Q., & Ruan, H. (1996).  Effects of the polysaccharides of Atractylis Macrocephala Koidz (PAM) on the proliferation of T-lymphocytes.   Journal of Immunology (12), 233-236.


Mao, J. & Lv, Z. (1995).  Functional regulations of cells by cyclic-GMP.   Progress in Biochemistry and Biophysics (22), 511-516.


Mao, J. & Lv, Z. (1995).  Mechanisms of the regulation of gene expression by the steroid hormone receptor superfamily.   Progress in Biochemistry and Biophysics (22), 202-207.


Lv, Z. & Zhang, W. (1993).  Roles of G proteins in the transmembrane signal transduction of cells.   The Chinese Journal of Cell Biology (15), 98-102.


Lv, Z., Xu, J., Yi, N., & Xia, Z. (1993).  Effects of thyroid hormone on the turnover of the cardiac ?-adrenoceptors in mice.   Basic Medicine and Clinics (13), 373-380.


Lv, Z. & Zhang, W. (1992).  Structure and function of the ?-adrenergic receptors.   Progress in Biochemistry and Biophysics (19), 417-422.


Yi, N., Xiao, Z., ., ., ., ., Lv, Z., et al. (1992).  Effects of zhimu and its sapogenin on the ?-adrenoceptor numbers and cAMP responses in mice.   Pharmacology and Therapeutics of Chinese Materia Medica (18), 40-48.


Lv, Z., Xu, J., Yi, N., & Xia, Z. (1992).  Effects of zhimu on the turnover of the cardiac ?-adrenoceptors of the hyperthyroid mice.   Nuclear Techniques (15), 651-656.


Xiao, Z., Zhang, S., Wu, Y., ., ., Lv, Z., et al. (1992).  Development of the ?2-adrenogeric receptor binding assay of the lymphocytes using (-)125I-pindolol.   The Chinese Journal of Nuclear Medicine (12), 99-106.


Lv, Z., Yi, N., & Xia, Z. (1991).  Synthesis of bromoacetylalprenololmenthane (BALpM), an irreversible inhibitor of the ?-adrenergic receptors.   Acta Pharmaceutica Sinica (26), 64-66.


Lv, Z., Yang, B., & Fang, R. (1989).  Studies on the antifertility effects of testosterone undecanoate in combination with danazol in male rats.   Acta Academiae Medicinae Sinicae (11), 190-194.


Publications 

Zhang (Editor-in-Chief), W., Lv (Editorial Member), Z., & et al., . (1998).  Biochemical Research Technology of Glycobiology, 2nd Edition Zhejiang University Press.  


Zhang (Editor-in-Chief), W., Lv (Editorial Member), Z., & et al., . (1994).  Biochemical Research Technology of Glycobiology, 1st Edition Zhejiang University Press.  


Publications 

Millar, R., Lv, Z., & Pawson, A. (2010). Gonadotropin-release hormone. Endocrinology 6th Edition, DeGroot LJ and Jameson JL. Philadelphia:  Elsevier. 


Millar, R., Pawson, A., Lv, Z., Morgan, K., Davidson, L., Lopez de Maturana R, Naor Z, Brown P and Maudsley S, (2004). Unknown. New concepts in GnRH receptor function, Updates in Infertility Treatment, Proceedings of the Conference (pp. 51-61). Italy:  Medimond, Pianoro. 


Hulme, E., Lv, Z., Saldanha, J., & Bee, M. (2004). Structure and activation of muscarinic acetylcholine receptors. Cholinergic Mechanisms: Function and Dysfunction (pp. 55-62). Taylor and Francis. 


Mao, J., Lv, Z., & Zheng, Q. (1996). Regulation of the polysaccharides of Atractylis Macrocephala Koidz (PAM) on immune function. Sheng Ming Ke Xue Yan Jiu Huo Ying Yong (pp. 668). Zhejiang University. 


Research Grants 

Other

2006: Coetsee, M. & Lv, Z., Commonwealth Scholarship (2006, to Marla Coetsee), Principal Investigator. 18,000 sterling pounds (PhD supervisor).


Research

2015: Liu, H., Lu, Z., & Meng, J., Regulation of T cell receptor (TCR) signalling by sumoylation of immune adaptor SLP-76, Co-Investigator, National Science Fundation of China (NSFC).


2014 [Year 1 of 4]: Lv, Z. & Rong, R., Molecular mechanisms of ligand-induced selective signalling at the gonadotropin-releasing hormone receptor, Principal Investigator, National Science Foundation of China (NSFC). 2014-2017: 650,000 RMB.


2006 [Year 5 of 5]: Lv, Z. Molecular/structural basis of ligand-induced selective signalling of G protein-coupled receptors in reproduction/cancer, Principal Investigator, Medical Research Council (MRC) UK. 2006-2011: 1,750,000 sterling pounds.


2006: Millar, R. & Lv, Z., Development of novel GnRH analogues, Co-Investigator. 2006-2008: 400,000 sterling pounds.


2001 [Year 5 of 5]: Lv, Z. Structure and function of GnRH and the human GnRH recepetor, Principal Investigator, Medical Research Council (MRC) UK. 2001-2006: 1,290,000 sterling pounds.


1996: Lv, Z. Systematic mutagenesis studies of the transmembrane domain 3 of the M1 muscarinic acetylcholine receptor, Principal Investigator, National Science Foundation of China (NSFC). 1996-1998: 105,000 RMB.


1995: Lv, Z. & Hulme, E., Alanine scanning mutagenesis studies of the M1 muscarinic acetylcholine receptor, Principal Investigator, Wellcome Trust. 1996-1997; 73,470 sterling pounds.


1994: Lv, Z. Effects of polysaccharides from Chinese herbs on the beta-adrenergic receptor-cAMP signalling cascade in immune cells, Principal Investigator, National Science Foundation of China (NSFC). 1994-1996: 65,000 RMB.

1991: Lv, Z. Structure and function of hCG and its receptor, Principal Investigator, Natural Science Foundation of Zhejiang Province