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Biography
Chloe J. Peach is an Assistant Professor in Molecular Pharmacology. She completed an undergraduate degree in Neuroscience at the University of Nottingham, before doing a Ph.D. in Molecular Pharmacology and Drug Discovery. Funded by the A.J. Clark Scholarship from the British Pharmacological Society, Dr. Peach identified novel distinctions in the spatial and temporal dynamics of how growth factors interact with a receptor tyrosine kinase (RTK) and a cell-surface glycoprotein involved in tumour angiogenesis. She then moved to the U.S.A. as a postdoctoral fellow in the Department of Molecular Pathobiology at New York University, studying both G protein-coupled receptors (GPCRs) and RTKs involved in chronic pain to explore non-opioid alternatives for analgesia. Funded by the prestigious Leon Levy Fellowship in Neuroscience, her postdoctoral work discovered a glycoprotein involved in transmitting growth factor-induced pain. Dr. Peach has won multiple awards, including the University of Nottingham Ian Tomlin Prize, the British Pharmacological Society Vogt Prize, as well as 5+ presentation awards. In the Summer of 2023, she returned to the University of Nottingham to establish her own research group in the School of Life Sciences. As part of the Centre of Membrane Proteins and Receptors (COMPARE), the Peach Lab is interested in the spatial and temporal dynamics of RTK pharmacology, particularly how the unique local microenvironment can modulate the pharmacology of these key prospective drug targets.
Expertise Summary
Despite major advances in our understanding of human biology, over 90% of drugs fail clinical trials. Many drugs target receptors, as membrane proteins that detect extracellular stimuli and evoke intracellular responses. RTKs are a family of 59 membrane proteins that respond to growth factors. These large ligands trigger signalling cascades that lead to cell proliferation, avoidance of cell death and initiation of migratory processes. They are therefore major targets in the field of oncology, however RTKs have wide-reaching pathological implications. Neurotrophins, for example, are a family of growth factors that stimulate neuronal growth. These growth factors, as well as the receptors, are promising targets for the treatment of neurodegenerative disease (agonists) or chronic pain (antagonists), however they lack clinically approved drugs.
Pharmacologists have largely focused on developing drugs for smaller membrane proteins (e.g., GPCRs) due to their relative ease to study in vitro and effectively manipulate using small molecules. As a result, there is limited pharmacological understanding of the vast majority of the RTK family. We have demonstrated that RTK biology is highly dynamic, travelling around living cells in real-time and exposing receptors to a range of distinct biochemical microenvironments. Receptors are, however, often considered in isolation from their local context in drug development. The Peach Lab sets out to explore how these unique local microenvironments modulate pharmacology, with an ultimate goal to develop better therapeutics that target RTKs across disease states.
Selected Publications
HEGRON A*, PEACH CJ*, TONELLO R*, SEEMANN P*, TENG S, LATORRE R, HUEBNER H, WEIKERT D, RIENTJES J, VELDHUIS NA, POOLE DP, JENSEN DJ, THOMSEN ARB, SCHMIDT BL, IMLACH W, GMEINER P and BUNNETT NW, 2023. Therapeutic Antagonism of the Neurokinin 1 Receptor in Endosomes Provides Sustained Pain Relief Proceedings of the National Academy of Sciences (PNAS). PEACH, CJ, EDGINGTON-MITCHELL, LE, BUNNETT, NW and SCHMIDT, BL, 2022. Protease-Activated Receptors in Health and Disease Physiological Reviews.