Professor Davide Calebiro MD PhD DSc

Professor Davide Calebiro

Institute of Metabolism and Systems Research
Professor of Molecular Endocrinology
Co-Director of the Centre of Membrane Proteins and Receptors (COMPARE)
Wellcome Trust Senior Research Fellow

Contact details

Address
Institute of Metabolism and Systems Resarch
College of Medical and Dental Sciences
Edgbaston
Birmingham
B15 2TT

Davide Calebiro is a Professor of Molecular Endocrinology and Wellcome Trust Senior Research Fellow at the Institute of Metabolism and Systems Research (IMSR) and Co-Director of the Centre of Membrane Proteins and Receptors (COMPARE) of the Universities of Birmingham and Nottingham

He leads a multidisciplinary research team comprising biologists, chemists, physicists, engineers and computer scientists focusing on the basic mechanisms of G protein-coupled receptor (GPCR) signalling and their alterations in endocrine and metabolic diseases. To study GPCR signalling in cells and tissues, they develop and use innovative optical methods based on FRET and single-molecule microscopy, which allow them to directly observe signalling events in living cells with unprecedented spatiotemporal resolution.

His major scientific contributions include the discovery that GPCRs are not only active at the plasma membrane but also at intracellular sites and that these receptors interact among themselves and with other membrane proteins to form dynamic nanodomains at the plasma membrane.

Davide has published 60 research papers, many of which in prestigious scientific journals, attracting several prizes and awards. He is serving on multiple panels and committees, including the Programme Committee of the Society for Endocrinology and the MRC Molecular & Cellular Medicine Board.

Qualifications

  • DSc in Pharmacology and Toxicology 2015
  • PhD in Molecular Medicine 2009
  • CCT in Endocrinology and Metabolic Diseases 2006
  • MD 2001

Biography

Professor Calebiro studied Medicine in Milan and Stockholm and obtained a Clinical Specialization in Endocrinology and Metabolic Diseases as well as a PhD in Molecular Medicine from the University of Milan. From 2009 to 2018, he led a research group at the Institute of Pharmacology and Bio-Imaging Center of Würzburg University, Germany. He joined the University of Birmingham in 2017, supported by a Birmingham Professorial Fellowship. In 2018, he has been awarded a prestigious Wellcome Trust Senior Research Fellowship.

Teaching

Postgraduate supervision

Davide Calebiro acts as primary and secondary supervisor for basic scientists and clinical research training fellows and is a supervisor in the MRC IMPACT Doctoral Training Programme.

Research

The Calebiro group investigates the basic mechanisms of G protein-coupled receptor (GPCR) signalling and their alterations in metabolic and endocrine disease.

A key focus is the development of innovative microscopy methods (such as FRET and single-molecule microscopy), in combination with new biosensors, to monitor receptor signalling directly in living cells and tissues with unprecedented spatiotemporal resolution. This is combined with novel mathematical and computational approaches to extract quantitative information from complex imaging data and model receptor signalling at both molecular and cellular level.

Using this multi-disciplinary approach, the Calebiro group has redefined fundamental mechanisms of GPCR signalling, including the important discovery that GPCRs are not only active at the plasma membrane, as previously thought, but also at intracellular sites such as endosomes and the Golgi complex. These findings challenge the classical model of GPCR signalling and could lead to novel drugs with improved efficacy and less side effects.

Moreover, the Calebiro group has a long-standing experience in the investigation of genetic alterations in GPCR signalling. This has led to the identification of genetic causes of disease, including the discovery that activating mutations in the catalytic α subunit of protein kinase A (PRKACA) are responsible for cortisol-secreting adrenocortical adenomas leading to Cushing’s syndrome.

The ultimate goal of the Calebiro group is to advance our understanding of the molecular and cellular mechanisms of GPCR signalling in order to devise innovative pharmacological therapies for endocrine and metabolic diseases.

This video shows single-molecule imaging of individual receptors and G proteins at the surface of a living cell.
Receptors (green) and G proteins (magenta) were labelled with small organic fluorophores, imaged by TIRF microscopy and tracked as they diffuse and interact on the plasma membrane.

Figure 1: Actin filaments provide barriers to receptor diffusion on the plasma membrane. Shown are trajectories of individual receptors (green) overlaid on a superresolved (PALM) image of the actin cytoskeleton (orange). Modified from Sungkaworn et al. Nature 2017. 

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Figure 2: Hot spots for GPCR signalling on the surface of living cells as revealed by single-molecule microscopy. Each dot corresponds to an interaction between a receptor and a G protein. Modified from Sungkaworn et al. Nature 2017.

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Figure 3: GPCRs signalling in the trans-Golgi network captured by a nanobody recognizing the active Gs protein (Nb37; orange). Modified from Godbole et al. Nat. Commun. 2017

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Current group members:

Zsombor Koszegi
Shannon O’Brien
Yann Lanoiselée
Tama Miljus
Jak Grimes
Emma Tripp
Ravi Mistry 

Research Groups and Centres

Follow Davide Calebiro on Twitter @DavideCalebiro

Our Centre of Membrane Proteins and Receptors (COMPARE)

Other activities

Local committees (selected):

Member, IMSR Executive Committee
Member, COMPARE Management Board

Clinical activities:

Honorary Consultant in Endocrinology, University Hospitals Birmingham NHS Foundation Trust 

National Committees (selected):

Member, MRC Molecular & Cellular Medicine Board (MCMB)
Member, Society for Endocrinology Programme Committee

Publications

Recent publications

Article

Walker, C, Wang, Y, Olivieri, C, V.S, M, Gao, J, Bernlohr, DA, Calebiro, D, Taylor, SS & Veglia, G 2021, 'Is disrupted nucleotide-substrate cooperativity a common trait for Cushing's syndrome driving mutations of protein kinase A?', Journal of Molecular Biology, vol. 433, no. 18, 167123. <http://10.1016/j.jmb.2021.167123>

Sveidahl Johansen, O, Ma, T, Hansen, JB, Markussen, LK, Schreiber, R, Reverte-salisa, L, Dong, H, Christensen, DP, Sun, W, Gnad, T, Karavaeva, I, Nielsen, TS, Kooijman, S, Cero, C, Dmytriyeva, O, Shen, Y, Razzoli, M, O’brien, SL, Kuipers, EN, Nielsen, CH, Orchard, W, Willemsen, N, Jespersen, NZ, Lundh, M, Sustarsic, EG, Hallgren, CM, Frost, M, Mcgonigle, S, Isidor, MS, Broholm, C, Pedersen, O, Hansen, JB, Grarup, N, Hansen, T, Kjær, A, Granneman, JG, Babu, MM, Calebiro, D, Nielsen, S, Rydén, M, Soccio, R, Rensen, PCN, Treebak, JT, Schwartz, TW, Emanuelli, B, Bartolomucci, A, Pfeifer, A, Zechner, R, Scheele, C, Mandrup, S & Gerhart-hines, Z 2021, 'Lipolysis drives expression of the constitutively active receptor GPR3 to induce adipose thermogenesis', Cell, vol. 184, no. 13, pp. 3502-3518.e33. https://doi.org/10.1016/j.cell.2021.04.037

Weigand, I, Ronchi, C, Vanselow, JT, Bathon, K, Lenz, K, Herterich, S, Schlosser, A, Kroiss, M, Fassnacht, M, Calebiro, D & Sbiera, S 2021, 'PKA Cα subunit mutation triggers caspase-dependent RIIβ subunit degradation via Ser114 phosphorylation', Science Advances, vol. 7, no. 8, eabd4176. https://doi.org/10.1126/sciadv.abd4176

Husted, AS, Ekberg, J, Tripp, E, Nissen, T, Meijnikman, S, O'Brien, S, Ulven, T, Acherman, Y, Bruin, S, Nieuwdorp, M, Gerhart-Hines, Z, Calebiro, D, Dragsted, L & Schwartz, T 2020, 'Autocrine negative feedback regulation of lipolysis through sensing of NEFAs by FFAR4/GPR120 in WAT', Molecular metabolism, vol. 42, 101103. https://doi.org/10.1016/j.molmet.2020.101103

Calebiro, D, Koszegi, Z, Lanoiselee, Y, Miljus, T & O'Brien, S 2020, 'G protein-coupled receptor-G protein interactions: a single-molecule perspective', Physiological Reviews. https://doi.org/10.1152/physrev.00021.2020

Drougat, L, Settas, N, Ronchi, C, Bathon, K, Calebiro, D, Gutierrez, A, Haydar, S, Voutetakis, A, London, E, Faucz, FR & Stratakis, C 2020, 'Genomic and sequence variants of protein kinase A regulatory subunit type 1β (PRKAR1B) in patients with adrenocortical disease and Cushing syndrome', Genetics in Medicine. https://doi.org/10.1038/s41436-020-00958-1

Pfeil, EM, Brands, J, Merten, N, Vogtle, T, Vescovo, M, Rich, U, Albrecht, I-M, Heycke, N, Kawakami, K, Ono, Y, Kadji, FMN, Hiratsuka, S, Aoki, J, Haberlein, F, Matthey, M, Garg, J, Hennen, S, Jobin, M-L, Seier, K, Calebiro, D, Pfeifer, A, Heinemann, A, Wenzel, D, Konig, G, Nieswandt, B, Fleischmann, B, Inoue, A, Simon, AK & Kostenis, E 2020, 'Heterotrimeric G protein subunit Gαq is a master switch for Gβγ-mediated calcium mobilization by Gi-coupled GPCRs', Molecular Cell, vol. 80, no. 6, pp. 940-954.e6. https://doi.org/10.1016/j.molcel.2020.10.027

Drakopoulos, A, Koszegi, Z, Lanoiselee, Y, Hubner, H, Gmeiner, P, Calebiro, D & Decker, M 2020, 'Investigation of inactive state κ opioid receptor homodimerization via single molecule microscopy using new antagonistic fluorescent probes', Journal of Medicinal Chemistry, vol. 63, no. 7, pp. 3596-3609. https://doi.org/10.1021/acs.jmedchem.9b02011

Espiard, S, Drougat, L, Settas, N, Haydar, S, Bathon, K, London, E, Levy, I, Faucz, FR, Calebiro, D, Bertherat, J, Li, D, Levine, M & Stratakis, C 2020, 'PRKACB variants in skeletal disease or adrenocortical hyperplasia: effects on protein kinase A', Endocrine-related cancer. https://doi.org/10.1530/ERC-20-0309

Siddig, S, Aufmkolk, S, Doose, S, Jobin, M-L, Werner, C, Sauer, M & Calebiro, D 2020, 'Super-resolution imaging reveals the nanoscale organization of metabotropic glutamate receptors at presynaptic active zones', Science Advances, vol. 6, no. 16, eaay7193. https://doi.org/10.1126/sciadv.aay7193 Article

Ast, J, Arvaniti, A, Fine, NHF, Nasteska, D, Ashford, FB, Stamataki, Z, Koszegi, Z, Bacon, A, Jones, BJ, Lucey, MA, Sasaki, S, Brierley, DI, Hastoy, B, Tomas, A, D’agostino, G, Reimann, F, Lynn, FC, Reissaus, CA, Linnemann, AK, D’este, E, Calebiro, D, Trapp, S, Johnsson, K, Podewin, T, Broichhagen, J & Hodson, DJ 2020, 'Super-resolution microscopy compatible fluorescent probes reveal endogenous glucagon-like peptide-1 receptor distribution and dynamics', Nature Communications, vol. 11, no. 1, 467 . https://doi.org/10.1038/s41467-020-14309-w

Buenaventura, T, Bitsi, S, Laughlin, WE, Burgoyne, T, Lyu, Z, Oqua, AI, Norman, H, McGlone, ER, Klymchenko, AS, Corrêa, IR, Walker, A, Inoue, A, Hanyaloglu, A, Grimes, J, Koszegi, Z, Calebiro, D, Rutter, GA, Bloom, SR, Jones, B & Tomas, A 2019, 'Agonist-induced membrane nanodomain clustering drives GLP-1 receptor responses in pancreatic beta cells', PLoS Biology, vol. 17, no. 8, pp. e3000097. https://doi.org/10.1371/journal.pbio.3000097

Bathon, K, Wigand, I, Vanselow, JT, Ronchi, C, Sbiera, S, Schlosser, A, Calebiro, D & Fassnacht, M 2019, 'Alterations in protein kinase A substrate specificity as a potential cause of Cushing’s Syndrome', Endocrinology, vol. 160, no. 2, pp. 447-459. https://doi.org/10.1210/en.2018-00775

Walker, C, Wang, Y, Olivieri, C, Karamafrooz, A, Casby, J, Bathon, K, Calebiro, D, Gao, J, Bernlohr, DA, Taylor, SS & Veglia, G 2019, 'Cushing’s syndrome driver mutation disrupts protein kinase A allosteric network, altering both regulation and substrate specificity', Science Advances, vol. 5, no. 8, eaaw9298. https://doi.org/10.1126/sciadv.aaw9298

Review article

Calebiro, D 2020, 'EJE AWARD 2020: Signalling by G protein coupled receptors: why space and time matter', European Journal of Endocrinology, vol. 0, pp. 1-23. https://doi.org/10.1530/EJE-20-0890

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