People_
Professor Robert Vandenberg
Professor
Director of Academic Career Development
Director of Academic Career Development
Phone
+61 2 9351 6734
Details
Member of The Centre for Drug Discovery Innovation
Rob Vandenberg received his PhD in Biochemistry at the University of Sydney in 1989 and then did his first postdoc at the Garvan Institute, working with Peter Schofield and John Shine to understand the agonist/antagonist interactions with the Glycine Receptor.
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Professor Vandenberg's research interests have focused on understanding how neurotransmitter transporters and receptors work. These proteins play key roles in regulating neurotransmission in the brain and are also the targets of a number of theraputic drugs and drugs of abuse. The laboratory uses a number of state-of-the-art molecular and biophysical techniques to address questions as to how these proteins bind neurotransmitters, how drugs interact with and modulate transporters and how these processes go wrong in disease states, such as Chronic Pain, Schizophrenia and Ischemia following a stroke.
A major focus of our work is on the development of novel compounds that inhibit glycine transporters. These compounds represent a new class of transport inhibitors and show considerable potential as analgesics for the treatment of chronic pain. Rob Vandenberg leads a multi-pronged approach to the drug development program funded by the NHMRC and NIH (USA) which includes collaborators at USYD (Mac Christie, Sarasa Mohammadi), UTS (Tristan Rawling), ANU (Megan O'Mara), Albany College of Pharmacy in New York (Chris Cioffi) and the University of Copenhagen (Claus Loland). Our work encompasses drug design, medicinal chemistry, understanding mechanisms of inhibition, structural biology, molecular dynamics simulations, synaptic physiology and behavioural pharmacology. We are also investigating the pharmacokinetic properties of these compounds with the aim of developing drugs that can be used in the clinic.
We have recently expanded our research interest to study ligand gated ion channels as targets for mitocides and insectocides. We have programs designed to develop toxins to treat Varroa mite infections in honeybees and also for insectocides for erradicating fire ants
Rob Vandenberg's main teaching interests are in the molecular basis for neuropharmacology and neurophysiology.
Design and development of novel compounds that inhibit glycine transporters for the treatment of pain.
Identification of dual action allosteric glycine transport inhibitors/glycine receptor stimulators for the treatment of pain
Identify mitocides for the treatment of Varroa mites to protect Honeybees
Neurosciences and Mental Health, Healthy Ageing, Lifespan
(University of Copenhagen) USYD/University of Copenhagen Collaborative Grant with Prof Claus Loland Biophysical studies of neurotransmitter sodium symporters, to aid the development of novel CNS drugs | |
(Albany College of Medicine, Albany, NY) Collaboration with Chris Cioffi to develop novel Glycine Transport Inhibitors | |
(Atomwise Inc., San Francisco, CA) AIMS Award to develop novel Glycine Transport Inhibitors. Terry O'Brien is using an in silico screening method to identify novel compounds and then synthesize lead compounds for our group to test |
| Project title | Research student |
|---|---|
| Molecular Dynamics of Glutamate Transporters | Amy CHENG |
| The Lipid Allosteric Site: A Novel Drug Target for Solute Carrier 6 Transporters | Irina LOTSARIS |
Publications
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Book Chapters
- Carland, J., Edington, A., Scopelliti, A., Ryan, R., Vandenberg, R. (2013). Directed Mutagenesis in Structure Activity Studies of Neurotransmitter Transporters. In David Figurski (Eds.), Genetic Manipulation of DNA and Protein - Examples from Current Research, (pp. 167-184). Rijeka: InTech Publishers. [More Information]
- McKinzie, A., Ryan, R., Vandenberg, R. (2010). Site-Directed Mutagenesis in the Study of Membrane Transporters. In Qing Yan (Eds.), Membrane Transporters in Drug Discovery and Development: Methods and Protocols - Methods in Molecular Biology Volume 637, (pp. 277-293). New York: Humana Press. [More Information]
- Ryan, R., Mitrovic, A., Vandenberg, R. (2003). Site-directed mutagenesis in the study of membrane transportes. In Qing Yan (Eds.), Membrane Transporters: Methods and Protocols (Methods in Molecular Biology Vol. 227), (pp. 97-108). New Jersey, USA: Humana Press.
Journals
- Gallagher, C., Bishop, D., Lockwood, T., Rawling, T., Vandenberg, R. (2024). Methods for negating the impact of zinc contamination to allow characterization of positive allosteric modulators of glycine receptors. Frontiers in Molecular Neuroscience, 17, 1392715. [More Information]
- Frangos, Z., Wilson, K., Aitken, H., Chater, R., Vandenberg, R., O'Mara, M. (2023). Membrane cholesterol regulates inhibition and substrate transport by the glycine transporter, GlyT2. Life Science Alliance, 6(4). [More Information]
- Gallagher, C., Frangos, Z., Sheipouri, D., Shimmon, S., Duman, M., Jayakumar, S., Cioffi, C., Rawling, T., Vandenberg, R. (2023). Novel Phenylene Lipids That Are Positive Allosteric Modulators of Glycine Receptors and Inhibitors of Glycine Transporter 2. ACS Chemical Neuroscience, 14(15), 2634-2647. [More Information]
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Conferences
- Liu, L., Markus, I., Vandenberg, R., Murray, M., Burcher, E. (2003). Distribution, expression and functional activity of three tachykinin NK1 receptor isoforms from Bufo Marinus. Society for Neuroscience, Washington DC: Society for Neuroscience.
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2024
- Gallagher, C., Bishop, D., Lockwood, T., Rawling, T., Vandenberg, R. (2024). Methods for negating the impact of zinc contamination to allow characterization of positive allosteric modulators of glycine receptors. Frontiers in Molecular Neuroscience, 17, 1392715. [More Information]
2023
- Frangos, Z., Wilson, K., Aitken, H., Chater, R., Vandenberg, R., O'Mara, M. (2023). Membrane cholesterol regulates inhibition and substrate transport by the glycine transporter, GlyT2. Life Science Alliance, 6(4). [More Information]
- Gallagher, C., Frangos, Z., Sheipouri, D., Shimmon, S., Duman, M., Jayakumar, S., Cioffi, C., Rawling, T., Vandenberg, R. (2023). Novel Phenylene Lipids That Are Positive Allosteric Modulators of Glycine Receptors and Inhibitors of Glycine Transporter 2. ACS Chemical Neuroscience, 14(15), 2634-2647. [More Information]
- Chater, R., Quinn, A., Wilson, K., Frangos, Z., Sutton, P., Jayakumar, S., Cioffi, C., O'Mara, M., Vandenberg, R. (2023). The efficacy of the analgesic GlyT2 inhibitor, ORG25543, is determined by two connected allosteric sites. Journal of Neurochemistry. [More Information]
2022
- Peiser-Oliver, J., Evans, S., Adams, D., Christie, M., Vandenberg, R., Mohammadi, S. (2022). Glycinergic Modulation of Pain in Behavioral Animal Models. Frontiers in Pharmacology, 13. [More Information]
- Reid, K., Spaull, R., Salian, S., Barwick, K., Meyer, E., Zhen, J., Hirata, H., Sheipouri, D., Benkerroum, H., Gorman, K., Vandenberg, R., et al (2022). MED27, SLC6A7, and MPPE1 Variants in a Complex Neurodevelopmental Disorder with Severe Dystonia. Movement Disorders, 37(10), 2139-2146. [More Information]
- Wilson, B., Peiser-Oliver, J., Gillis, A., Evans, S., Alamein, C., Mostyn, S., Shimmon, S., Rawling, T., Christie, M., Vandenberg, R., Mohammadi, S. (2022). Peripheral Administration of Selective Glycine Transporter-2 Inhibitor, Oleoyl-
D -Lysine, Reverses Chronic Neuropathic Pain but Not Acute or Inflammatory Pain in Male Mice. Journal of Pharmacology and Experimental Therapeutics, 382(3), 246-255. [More Information]
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2021
- Chen, I., Pant, S., wu, Q., Cater, R., Sobti, M., Vandenberg, R., Stewart, A., Tajkhorshid, E., Font Sadurni, J., Ryan, R. (2021). Glutamate transporters have a chloride channel with two hydrophobic gates. Nature, 591(7849), 327-331. [More Information]
- Frangos, Z., Chater, R., Vandenberg, R. (2021). Glycine Transporter 2: Mechanism and Allosteric Modulation. Frontiers in Molecular Biosciences, 8, 734427. [More Information]
- Harvey, R., Vandenberg, R. (2021). Glycine transporters and receptors as targets for analgesics. Biomolecules, 11(11), 1676. [More Information]
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2020
- Sheipouri, D., Gallagher, C., Shimmon, S., Rawling, T., Vandenberg, R. (2020). A system for assessing dual action modulators of glycine transporters and glycine receptors. Biomolecules, 10(12), 1-25. [More Information]
- Freidman, N., Chen, I., wu, Q., Briot, C., Holst, J., Font Sadurni, J., Vandenberg, R., Ryan, R. (2020). Amino Acid Transporters and Exchangers from the SLC1A Family: Structure, Mechanism and Roles in Physiology and Cancer. Neurochemical Research, 45(6), 1268-1286. [More Information]
- Aubrey, K., Sheipouri, D., Balle, T., Vandenberg, R., Otsu, Y. (2020). Glutamate, D-(2)-2-Amino-5-phosphonopentanoic acid, and N-Methyl-D-Aspartate do not directly modulate glycine receptors. Molecular Pharmacology, 98(6), 719-729. [More Information]
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2019
- Mostyn, S., Rawling, T., Mohammadi, S., Shimmon, S., Frangos, Z., Sarker, S., Yousuf, A., Vetter, I., Ryan, R., Christie, M., Vandenberg, R. (2019). Development of an N-acyl amino acid that selectively inhibits the glycine transporter 2 to produce analgesia in a rat model of chronic pain. Journal of Medicinal Chemistry, 62(5), 2466-2484. [More Information]
- Mostyn, S., Wilson, K., Schumann-Gillett, A., Frangos, Z., Shimmon, S., Rawling, T., Ryan, R., O'Mara, M., Vandenberg, R. (2019). Identification of an allosteric binding site on the human glycine transporter, GlyT2, for bioactive lipid analgesics. eLife, 8, 1-22. [More Information]
2018
- Winters, B., Rawling, T., Vandenberg, R., Christie, M., Bhola, R., Imlach, W. (2018). Activity of novel lipid glycine transporter inhibitors on synaptic signalling in the dorsal horn of the spinal cord. British Journal of Pharmacology, 175(12), 2337-2347. [More Information]
- Carland, J., Thomas, M., Mostyn, S., Subramanian, N., O'Mara, M., Ryan, R., Vandenberg, R. (2018). Molecular Determinants for Substrate Interactions with the Glycine Transporter GlyT2. ACS Chemical Neuroscience, 9(3), 603-614. [More Information]
- Scopelliti, A., Font Sadurni, J., Vandenberg, R., Boudker, O., Ryan, R. (2018). Structural characterisation reveals insights into substrate recognition by the glutamine transporter ASCT2/SLC1A5. Nature Communications, 9(1), 1-12. [More Information]
2017
- Mostyn, S., Carland, J., Shimmon, S., Ryan, R., Rawling, T., Vandenberg, R. (2017). Synthesis and Characterization of Novel Acyl-Glycine Inhibitors of GlyT2. ACS Chemical Neuroscience, 8(9), 1949-1959. [More Information]
- Krycer, J., Fazakerley, D., Cater, R., Cooke, K., Naghiloo, S., Burchfield, J., Humphrey, S., Vandenberg, R., Ryan, R., James, D. (2017). The amino acid transporter SLC1A3 is plasma membrane-localised in adipocytes and its activity is insensitive to insulin. FEBS Letters, 591(2), 322-330. [More Information]
2016
- Vandenberg, R., Ryan, R., Broer, S. (2016). Brain transporters: From genes and genetic disorders to function and drug discovery. Neurochemistry International, 98, 1-3. [More Information]
- McIlwain, B., Vandenberg, R., Ryan, R. (2016). Characterization of the Inward- and Outward-Facing Substrate Binding Sites of the Prokaryotic Aspartate Transporter, GltPh. Biochemistry, 55(49), 6801-6810. [More Information]
- Ryan, R., Vandenberg, R. (2016). Elevating the alternating-access model. Nature Structural and Molecular Biology, 23(3), 187-189. [More Information]
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2015
- McIlwain, B., Vandenberg, R., Ryan, R. (2015). Transport rates of a glutamate transporter homologue are influenced by the lipid bilayer. Journal of Biological Chemistry, 290(15), 9780-9788. [More Information]
2014
- Vandenberg, R., Ryan, R., Carland, J., Imlach, W., Christie, M. (2014). Glycine transport inhibitors for the treatment of pain. Trends In Pharmacological Sciences, 35(8), 423-430. [More Information]
- Carland, J., Handford, C., Ryan, R., Vandenberg, R. (2014). Lipid Inhibitors of High Affinity Glycine Transporters: Identification of a novel class of analgesics. Neurochemistry International, 73, 211-216. [More Information]
- Scopelliti, A., Heinzelmann, G., Kuyucak, S., Ryan, R., Vandenberg, R. (2014). Na+ interactions with the neutral amino acid transporter. Journal of Biological Chemistry, 289(25), 17468-17479. [More Information]
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2013
- Carland, J., Edington, A., Scopelliti, A., Ryan, R., Vandenberg, R. (2013). Directed Mutagenesis in Structure Activity Studies of Neurotransmitter Transporters. In David Figurski (Eds.), Genetic Manipulation of DNA and Protein - Examples from Current Research, (pp. 167-184). Rijeka: InTech Publishers. [More Information]
- Vandenberg, R., Ryan, R. (2013). Mechanisms of glutamate transport. Physiological Reviews, 93(4), 1621-1657. [More Information]
- Scopelliti, A., Ryan, R., Vandenberg, R. (2013). Molecular Determinants for Functional Differences between Alanine-Serine-Cysteine Transporter 1 and Other Glutamate Transporter Family Members. Journal of Biological Chemistry, 288(12), 8250-8257. [More Information]
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2012
- Bastug, T., Heinzelmann, G., Kuyucak, S., Salim, M., Vandenberg, R., Ryan, R. (2012). Position of the Third Na+ Site in the Aspartate Transporter GltPh and the Human Glutamate Transporter, EAAT1. PloS One, 7(3), 1-10. [More Information]
2011
- Scott, H., Gebhardt, F., Mitrovic, A., Vandenberg, R., Dodd, P. (2011). Glutamate Transporter Variants Reduce Glutamate Uptake in Alzheimer's Disease. Neurobiology of Aging, 32(3), 553.e1-553.e11. [More Information]
- Bailey, C., Ryan, R., Theong, A., Ng, C., King, K., Vanslambrouck, J., Auray-Blais, C., Vandenberg, R., Bröer, S., Rasko, J. (2011). Loss-of-function mutations in the glutamate transporter SLC1A1 cause human dicarboxylic aminoaciduria. Journal of Clinical Investigation, 121(1), 446-453. [More Information]
- Vandenberg, R., Handford, C., Campbell, E., Ryan, R., Yool, A. (2011). Water and urea permeation pathways of the human excitatory amino acid transporter EAAT1. Biochemical Journal, 439(2), 333-340. [More Information]
2010
- Gebhardt, F., Mitrovic, A., Gilbert, D., Vandenberg, R., Lynch, J., Dodd, P. (2010). Exon-skipping splice variants of excitatory amino acid transporter-2 (EAAT2) form heteromeric complexes with full-length EAAT2. Journal of Biological Chemistry, 285(41), 31313-31324. [More Information]
- Connor, M., Vaughan, C., Vandenberg, R. (2010). N-Acyl amino acids and N-acyl neurotransmitter conjugates: neuromodulators and probes for new drug targets. British Journal of Pharmacology, 160(8), 1857-1871. [More Information]
- Jeong, H., Vandenberg, R., Vaughan, C. (2010). N-arachidonyl-glycine modulates synaptic transmission in superficial dorsal horn. British Journal of Pharmacology, 161(4), 925-935. [More Information]
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2009
- Edington, A., McKinzie, A., Reynolds, A., Kassiou, M., Ryan, R., Vandenberg, R. (2009). Extracellular loops 2 and 4 of GLYT2 are required for N-arachidonylglycine inhibition of glycine transport. Journal of Biological Chemistry, 284(52), 36424-36430. [More Information]
- Liu, X., Mitrovic, A., Vandenberg, R. (2009). Glycine transporter 1 associates with cholesterol-rich membrane raft microdomains. Biochemical and Biophysical Research Communications, 384(4), 530-534. [More Information]
- Habjan, S., Vandenberg, R. (2009). Modulation of glutamate and glycine transporters by niflumic, flufenamic and mefenamic acids. Neurochemical Research, 34(10), 1738-1747. [More Information]
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2008
- Vandenberg, R., Huang, S., Ryan, R. (2008). Slips, leaks and channels in glutamate transporters. Channels, 2(1), 51-58. [More Information]
- Yang, Z., Aubrey, K., Alroy, I., Harvey, R., Vandenberg, R., Lynch, J. (2008). Subunit-specific modulation of glycine receptors by cannabinoids and N-arachidonyl-glycine. Biochemical Pharmacology, 76(8), 1014-1023. [More Information]
2007
- Vandenberg, R., Shaddick, K., Ju, P. (2007). Molecular basis for substrate discrimination by glycine transporters. Journal of Biological Chemistry, 282(19), 14447-14453. [More Information]
- Huang, S., Vandenberg, R. (2007). Mutations in Transmembrane Domains 5 and 7 of the Human Excitatory Amino Acid Transporter 1 Affect the Substrate-Activated Anion Channel. Biochemistry, 46(34), 9685-9692. [More Information]
2006
- Vandenberg, R. (2006). Mutational analysis of glutamate transporters. Handbook of experimental pharmacology, 175(175), 113-35. [More Information]
- Wiles, A., Pearlman, R., Rosvall, M., Aubrey, K., Vandenberg, R. (2006). N-Arachidonyl-glycine inhibits the glycine transporter, GLYT2a. Journal of Neurochemistry, 99(3), 781-786. [More Information]
2005
- Ryan, R., Vandenberg, R. (2005). A channel in a transporter. Clinical and Experimental Pharmacology and Physiology, 32(1-2), 1-6. [More Information]
- Aubrey, K., Vandenberg, R., Clements, J. (2005). Dynamics of forward and reverse transport by the glial glycine transporter, glyt1b. Biophysical Journal, 89(3), 1657-1668. [More Information]
- Vandenberg, R., Ryan, R. (2005). How and Why Are Channels in Transporters? Signal Transduction Knowledge Environment, 19(280), pe17. [More Information]
2004
- Vandenberg, R., Ju, P., Aubrey, K., Ryan, R., Mitrovic, A. (2004). Allosteric Modulation Of Neurotransmitter Transporters At Excitatory Synapses. European Journal of Pharmaceutical Sciences, 23(1), 1-11. [More Information]
- Liu, L., Markus, I., Vandenberg, R., Neilan, B., Murray, M., Burcher, E. (2004). Molecular Identification And Characterization Of Three Isoforms Of Tachykinin Nk(1)-Like Receptors In The Cane Toad Bufo Marinus. American Journal of Physiology - Regulatory Integrative and Comparative Physiology, 287(3), R575-R585. [More Information]
- Ryan, R., Mitrovic, A., Vandenberg, R. (2004). The Chloride Permeation Pathway Of A Glutamate Transporter And Its Proximity To The Glutamate Translocation Pathway. Journal of Biological Chemistry, 279(20), 20742-20751. [More Information]
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2003
- Pearlman, R., Aubrey, K., Vandenberg, R. (2003). Arachidonic acid and anandamide have opposite modulatory actions at the glycine transporter, GLYT1a. Journal of Neurochemistry, 84(3), 592-601. [More Information]
- Liu, L., Markus, I., Vandenberg, R., Murray, M., Burcher, E. (2003). Distribution, expression and functional activity of three tachykinin NK1 receptor isoforms from Bufo Marinus. Society for Neuroscience, Washington DC: Society for Neuroscience.
- Mitrovic, A., Vandenberg, R. (2003). Glutamate transporters: redefining the view of a transporter. Australian Biochemist, 11, 8-11.
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2002
- Ryan, R., Vandenberg, R. (2002). Distinct conformational states mediate the transport and anion channel properties of the glutamate transporter EAAT-1. Journal of Biological Chemistry, 277(16), 13494-13500. [More Information]
- El-Hajjmoussa, C., Mitrovic, A., Vandenberg, R., Provis, T., Rae, C., Bubb, W., Balcar, V. (2002). Effects of L-Glutamate Transport Inhibition by a Conformationally Restricted Glutamate Analogue (2S,1'S,2'R)-2-(Carboxycyclopropyl)Glycine (L-CCG III)on Metabolism in Brain Tissue In Vitro Analysed by NMR Spectroscopy. Neurochemical Research, 27, 27-35.
- Moussa, C., Mitrovic, A., Vandenberg, R., Provis, T., Rae, C., Bubb, W., Balcar, V. (2002). Effects of L-glutamate transport inhibition by a conformationally restricted glutamate analogue (2S,1"S,2'R)-2-(Carboxycyclopropyl) glycine (L-CCF III) on metabolism in brain tissue in vitro analysed by NMR spectroscopy. Neurochemical Research, 27(1), 27-35. [More Information]
2001
- Vandenberg, R., Aubrey, K. (2001). Glycine transport inhibitors as potential antipsychotic drugs. Expert Opinion on Therapeutic Targets, 5, 507-518.
- Aubrey, K., Vandenberg, R. (2001). N[3-(4-fluorophenyl)-3-(4'-phenylphenoxy) propyl]sarcosine (NFPS) is a selective persistent inhibitor of glycine transport. British Journal of Pharmacology, 134(7), 1429-1436. [More Information]
- Poulsen, M., Vandenberg, R. (2001). Niflumic acid modulates uncoupled substrate-gated conductances in the human glutamate transporter EAAT4. Journal of Physiology, 534, 159-167. [More Information]
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Selected Grants
2019
- Discovery and Development of Novel Glycine Transer-2 Inhibitors for the treatment of neuropathic pain, Cioffi C, Vandenberg R, Christie M, National Institutes of Health (USA)/Research Grant
2018
- The spilt personality of glutamate transporters: the structural basis and physiological role of a dual function transporter/channel, Ryan R, van Meyel D, Boudker O, Font Sadurni J, Vandenberg R, National Health and Medical Research Council (NHMRC)/Project Grants
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