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Biography
Rob Lane joined the University of Nottingham in October 2018 as an Assistant Professor in Molecular Pharmacology. Rob's work focuses on G protein-coupled receptors (GPCRs) with a particular emphasis on novel approaches to target these receptors towards the development of improved therapeutics for CNS disorders.
Rob completed his PhD in molecular pharmacology at the University of Glasgow in 2007. He then joined the department of Medicinal Chemistry at the University of Leiden as a postdoctoral fellow. There, he gained a VENI grant (NWO, the Netherlands) to begin his independent research career with a focus on understanding the structure and pharmacology of adenosine receptors. In 2010, Rob moved to the Monash Institute of Pharmaceutical Sciences, Melbourne, Australia as an R.D. Wright Biomedical Research Fellow (NHMRC, Australia) and Larkin's Fellow (Monash University). His research had a particular emphasis on exploring the paradigms of allosteric modulation and biased agonism. In 2017 he was awarded a Schaefer Scholarship to join the departments of Psychiatry & Pharmacology at Columbia University (New York, USA) as a visiting professor for a sabbatical year, hosted by Prof Jonathan Javitch. During this sabbatical he focused on developing selective genetic and pharmacological tools with which to understand the physiological consequences of dopamine receptor drug action. At the end of 2018, Rob moved his lab to the University of Nottingham, to join the Centre of Membrane Protein and Receptors (COMPARE), a joint venture between the University of Birmingham and the University of Nottingham.
Expertise Summary
G protein-coupled receptors (GPCRs) are involved in every physiological process and are the target of over one third of clinically used drugs. However, such drugs are often associated with deleterious side effects and the high attrition rate of GPCR drug discovery reflects our limited understanding of the function of these proteins. Our group has an emphasis on novel approaches to target these receptors towards the development of new ways to treat CNS disorders such as schizophrenia. In the pursuit of these objectives we are carrying out research on the dopamine D2 receptor as well as several other GPCRs. The dopamine D2 receptor is the principal target of antipsychotic drugs used in the treatment of schizophrenia and for some drugs used to treat the symptoms of Parkinson's disease. One main line of research in my laboratory is aimed at understanding the structural basis of drug binding and specificity in these receptors, how they modulate receptor function and ultimately dictate their physiological effect. A particular focus is on two paradigms of GPCR drug action that may be exploited to develop new drugs with greater target or tissue selectivity, allosteric modulation and biased agonism. The lab combines analytical pharmacology with advanced biochemical and imaging techniques to interrogate receptor function and signaling. Through close (inter)national collaborations with structural biologists, medicinal chemists and neuroscientists we are using these approaches to develop novel chemical and genetic tools with which we will address fundamental questions about GPCR drug action.
Selected Publications
LANE, J ROBERT, MAY, LAUREN T, PARTON, ROBERT G, SEXTON, PATRICK M and CHRISTOPOULOS, ARTHUR, 2017. A kinetic view of GPCR allostery and biased agonism: Nat Chem Biol Nat Chem Biol. 13(9), 929-937 KLEIN HERENBRINK, CARMEN, SYKES, DAVID A, DONTHAMSETTI, PRASHANT, CANALS, MERITXELL, COUDRAT, THOMAS, SHONBERG, JEREMY, SCAMMELLS, PETER J, CAPUANO, BEN, SEXTON, PATRICK M, CHARLTON, STEVEN J, JAVITCH, JONATHAN A, CHRISTOPOULOS, ARTHUR and LANE, J ROBERT, 2016. The role of kinetic context in apparent biased agonism at GPCRs.: Nature communications Nature communications. 7, 10842 LANE, J ROBERT, DONTHAMSETTI, PRASHANT, SHONBERG, JEREMY, DRAPER-JOYCE, CHRISTOPHER J, DENTRY, SAMUEL, MICHINO, MAYAKO, SHI, LEI, LÓPEZ, LAURA, SCAMMELLS, PETER J, CAPUANO, BEN, SEXTON, PATRICK M, JAVITCH, JONATHAN A and CHRISTOPOULOS, ARTHUR, 2014. A new mechanism of allostery in a G protein--coupled receptor dimer: Nat Chem Biol Nat Chem Biol. 10(9), 745-752 MISTRY, SN, SHONBERG, J, DRAPER-JOYCE, CJ, HERENBRINK, CK, MICHINO, M, SHI, L, CHRISTOPOULOS, A, CAPUANO, B, SCAMMELLS, PJ and LANE, JR, 2015. Discovery of a Novel Class of Negative Allosteric Modulator of the Dopamine D2 Receptor Through Fragmentation of a Bitopic Ligand Journal of Medicinal Chemistry.