Summary
Dr Alejandra Tomas is a Senior Lecturer at the Section of Cell Biology and Functional Genomics, part of the Department of Metabolism, Digestion and Reproduction, Imperial College London.
She obtained her PhD in Biochemistry at University College London in 2003, where she worked on the elucidation of the cellular roles of the calcium- and membrane-binding family of annexin proteins.
She then took up a postdoctoral position at the University of Geneva Medical School, Switzerland, where she analysed diverse aspects of the regulation of insulin secretion in pancreatic beta cells, primarily related to the role of the cytoskeleton in insulin exocytosis and the relationship between the secretory and endocytic pathways.
In 2009 she joined the Department of Biochemistry at the University of Geneva where she focused on the study of receptor trafficking along the endocytic pathway, an area of research she continued to develop back at UCL following her return to the UK in 2011.
In 2015, Alejandra was awarded a New Investigator Research Grant by the MRC to set up an independent research group at Imperial College London to study the role of membrane receptor trafficking in the modulation of signalling and function of pancreatic beta cells.
Since then, her laboratory has pursued a number of investigations related to the study of the spatiotemporal regulation of signalling of the GLP-1 receptor and other key receptors involved in the control of blood glucose levels and related metabolic parameters.
She is also a Director of the MSc Applied Genomics course.
Selected Publications
Journal Articles
Xiao J, El Eid L, Buenaventura T, et al., 2023, Control of human pancreatic beta cell kinome by glucagon-like peptide-1 receptor biased agonism, Diabetes Obesity & Metabolism, Vol:25, ISSN:1462-8902, Pages:2105-2119
Tomas Catala A, Bitsi S, Manchanda Y, et al., 2023, Divergent acute versus prolonged pharmacological GLP-1R responses in adult beta cell-specific β-arrestin 2 knockout mice, Science Advances, Vol:9, ISSN:2375-2548, Pages:1-23
de Jesus DS, Mak TCS, Wang Y-F, et al., 2021, Dysregulation of the Pdx1/Ovol2/Zeb2 axis in dedifferentiated β-cells triggers the induction of genes associated with epithelial-mesenchymal transition in diabetes, Molecular Metabolism, Vol:53, ISSN:2212-8778
McGlone ER, Manchanda Y, Jones B, et al., 2021, Receptor Activity-Modifying Protein 2 (RAMP2) alters glucagon receptor trafficking in hepatocytes with functional effects on receptor signalling, Molecular Metabolism, Vol:53, ISSN:2212-8778, Pages:1-11
Lucey M, Ashik T, Marzook A, et al., 2021, Acylation of the incretin peptide exendin-4 directly impacts GLP-1 receptor signalling and trafficking, Molecular Pharmacology, Vol:100, ISSN:0026-895X, Pages:319-334
Pickford P, Lucey M, Rujan R-M, et al., 2021, Partial agonism improves the anti-hyperglycaemic efficacy of an oxyntomodulin-derived GLP-1R/GCGR co-agonist, Molecular Metabolism, Vol:51, ISSN:2212-8778
Marzook A, Chen S, Pickford P, et al., 2021, Evaluation of efficacy- versus affinity-driven agonism with biased GLP-1R ligands P5 and exendin-F1, Biochemical Pharmacology, Vol:190, ISSN:0006-2952, Pages:1-12
Cheung R, Pizza G, Chabosseau P, et al., 2021, Glucose-dependent miR-125b is a negative regulator of β-cell function, Biorxiv
Marzook A, Tomas A, Jones B, 2021, The interplay of glucagon-like peptide-1 receptor trafficking and signalling in pancreatic beta cells, Frontiers in Endocrinology, Vol:12, ISSN:1664-2392, Pages:1-12
Arcones AC, Vila-Bedmar R, Mirasierra M, et al., 2021, GRK2 regulates GLP-1R-mediated early phase insulin secretion in vivo, BMC Biology, Vol:19, ISSN:1741-7007
Manchanda Y, Bitsi S, Kang Y, et al., 2021, Spatiotemporal control of GLP-1 receptor activity, Current Opinion in Endocrine and Metabolic Research, Vol:16, ISSN:2451-9650, Pages:19-27
Lagou V, Jiang L, Ulrich A, et al., 2021, Random glucose GWAS in 493,036 individuals provides insights into diabetes pathophysiology, complications and treatment stratification, Medrxiv
Jones B, McGlone ER, Fang Z, et al., 2021, Genetic and biased agonist-mediated reductions in β-arrestin recruitment prolong cAMP signalling at glucagon family receptors, Journal of Biological Chemistry, Vol:296, ISSN:0021-9258, Pages:1-15
Georgiadou E, Muralidharan C, Martinez M, et al., 2021, Mitofusins Mfn1 and Mfn2 are required to preserve glucose-but not incretin- stimulated beta cell connectivity and insulin secretion, Biorxiv
Jones B, Fang Z, Chen S, et al., 2020, Ligand-specific factors influencing GLP-1 receptor post-endocytic trafficking and degradation in pancreatic beta cells, International Journal of Molecular Sciences, Vol:212, ISSN:1422-0067, Pages:1-24
Ast J, Arvaniti A, Fine NHF, et al., 2020, Author Correction: Super-resolution microscopy compatible fluorescent probes reveal endogenous glucagon-like peptide-1 receptor distribution and dynamics., Nature Communications, Vol:11, ISSN:2041-1723, Pages:1-1
Carrat GR, Haythorne E, Tomas A, et al., 2020, The type 2 diabetes gene product STARD10 is a phosphoinositide-binding protein that controls insulin secretory granule biogenesis, Molecular Metabolism, Vol:40, ISSN:2212-8778
Pickford P, Lucey M, Fang Z, et al., 2020, Signalling, trafficking and glucoregulatory properties of glucagon-like peptide-1 receptor agonists exendin-4 and lixisenatide., British Journal of Pharmacology, Vol:177, ISSN:0007-1188, Pages:3905-3923
Jones B, Pickford P, Lucey M, et al., 2020, Disconnect between signalling potency and in vivo efficacy of pharmacokinetically optimised biased glucagon-like peptide-1 receptor agonists, Molecular Metabolism, Vol:37, ISSN:2212-8778
Fang Z, Chen S, Pickford P, et al., 2020, The influence of peptide context on signaling and trafficking of glucagon-like peptide-1 receptor biased agonists, Acs Pharmacology & Translational Science, Vol:3, ISSN:2575-9108, Pages:345-360
Tomas A, Jones B, Leech C, 2020, New insights into beta cell GLP-1 receptor and cAMP signaling, Journal of Molecular Biology, Vol:432, ISSN:0022-2836, Pages:1347-1366
Khan R, Tomas A, Rutter GA, 2020, Effects on pancreatic Beta and other Islet cells of the glucose-dependent insulinotropic polypeptide, Peptides, Vol:125, ISSN:0196-9781
Ast J, Arvaniti A, Fine NHF, et al., 2020, Super-resolution microscopy compatible fluorescent probes reveal endogenous glucagon-like peptide-1 receptor distribution and dynamics, Nature Communications, Vol:11, ISSN:2041-1723
Xu W, Ashford FB, Bitsi S, et al., 2020, Testosterone enhances GLP-1 efficacy at the plasma membrane and endosomes to augment insulin secretion in male pancreatic β cells, Biorxiv
Fremaux J, Venin C, Mauran L, et al., 2019, Ureidopeptide GLP-1 analogues with prolonged activity in vivo via signal bias and altered receptor trafficking, Chemical Science, Vol:42, ISSN:2041-6520, Pages:9872-9879
Buenaventura T, Bitsi S, Laughlin WE, et al., 2019, Agonist-induced membrane nanodomain clustering drives GLP-1 receptor responses in pancreatic beta cells., PLOS Biology, Vol:17, ISSN:1544-9173, Pages:1-40
Watson S, Duff J, Bardi I, et al., 2019, Biomimetic electromechanical stimulation to maintain adult myocardial slices in vitro, Nature Communications, Vol:10, ISSN:2041-1723
Pernaute B, Sánchez Nieto JM, Pérez-Montero S, et al., 2019, DRP1-mediated regulation of mitochondrial dynamics determines the apoptotic response upon embryonic differentiation, Biorxiv
Jones B, Buenaventura T, Kanda N, et al., 2018, Targeting GLP-1 receptor trafficking to improve agonist efficacy, Nature Communications, Vol:9, ISSN:2041-1723
Jones B, Bloom S, Buenaventura T, et al., 2018, Control of insulin secretion by GLP-1, Peptides, Vol:100, ISSN:0196-9781, Pages:75-84
Podewin T, Ast J, Broichhagen J, et al., 2018, Conditional and reversible activation of class A and B G protein-coupled receptors using tethered pharmacology, Acs Central Science, Vol:4, ISSN:2374-7943, Pages:166-179
Buenaventura T, Kanda N, Douzenis PC, et al., 2017, A targeted RNAi screen identifies endocytic trafficking factors that control GLP-1 receptor signaling in pancreatic beta cells, Diabetes, Vol:67, ISSN:0012-1797, Pages:385-399
Jones BJ, Scopelliti R, Tomas A, et al., 2017, Potent prearranged positive allosteric modulators of the glucagon-like peptide-1 receptor, Chemistryopen, Vol:6, ISSN:2191-1363, Pages:501-505