Professor Davide Calebiro MD PhD DSc

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

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.

• MBChB – Cell Communication: Endocrinology and Pharmacology
• MPharm – Health, Disease & Therapeutics
• BSc Biochemistry, BSc Medical Biochemistry, BSc Human Biology – Cell Signalling

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.

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. 

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.

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

 

Current group members:

Zsombor Koszegi
Shannon O’Brien
Yann Lanoiselée
Tamara Miljus
Jak Grimes
Emma Tripp
Edalat Radfar

Research Groups and Centres

Follow Davide Calebiro on Twitter @DavideCalebiro

Our Centre of Membrane Proteins and Receptors (COMPARE)

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