Role and Modulation of Canonical and Atypical Chemokine Receptors

Chair: Martine Smit 

Vrije Universiteit Amsterdam, Department of Chemistry and Pharmaceutical Sciences, The Netherlands

Martine Smit is a globally recognized expert in GPCR signaling and oncogenic networks, with a distinguished career in drug discovery and the modulation of human and viral chemokine receptors. She leads the ONCORNET2.0 consortium, where her research focuses on the pivotal chemokine receptors CXCR4 and ACKR3, which play key roles in cancer progression. With her team, Prof. Smit has spearheaded innovative therapeutic approaches such as photochemistry and nanobodies to modulate GPCR function.

This session will feature an introduction to the ONCORNET consortium and dive into the latest research on these critical receptors in the context of cancer biology. 

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Chair: Nicole Scholz

University of Leipzig, Rudolf Schönheimer Institute of Biochemistry, Germany

Nicole Scholz leads pioneering research aimed at understanding the alternative splicing of Adhesion GPCR mRNAs and their interactions with other cell surface molecules to drive neuronal mechanophysiology. Her work explores how these receptors contribute to cellular health and what goes wrong when Adhesion GPCRs malfunction, especially in the context of mechanopathologies—diseases where mechanical properties of cells and tissues are disrupted.

Chair: Nathan Zaidman

University of New Mexico, Biochemistry & Molecular Biology, USA 

Nathan Zaidman began his research on Adhesion GPCRs during his postdoctoral work at Johns Hopkins University, where he studied ADGRF5/GPR116 in the kidney. His work has uncovered GPR116’s critical role in regulating proton pumps in A-type intercalated cells, with direct implications for urine acidification and metabolic processes. His future research aims to expand on these findings, investigating the roles of other Adhesion GPCRs in renal physiology and their regulation at the transcriptional level.

The Adhesion GPCR Consortium (AGC) is an international, open network of laboratories interested in Adhesion GPCRs. The specific aim is the promotion of scientific knowledge, particularly in the field of these nonclassical GPCRs.  Activities include meeting organization, generating a knowledge base for Adhesion GPCR research, and the exchange of trainees, graduate students, and postdocs.

This session will delve into the history of the Adhesion GPCR field and give insight into the molecular principles underlying the physiology and pathology of these huge cell surface receptors.

The Centre of Membrane Proteins and Receptors (UK)

Chair: Davide Calebiro 

University of Birmingham, Department of Metabolism and Systems Science, UK

Davide Calebiro has pioneered the use of advanced optical methods based on FRET/BRET and single-molecule microscopy to study GPCR signalling in living cells with unprecedented spatiotemporal resolution. Using these approaches, his group was among the first to demonstrate that GPCRs are not only active at the plasma membrane but also in the endosomal compartment, which has challenged the classical model of GPCR signalling.

Ongoing work in the Calebiro lab is dedicated to further clarifying the physiological and pharmacological implications of GPCR signalling at intracellular sites, with a particular focus on metabolically relevant GPCRs, and the dynamic organisation of GPCR signalling nanodomains at the plasma membrane.

The Centre of Membrane Proteins and Receptors (COMPARE) is a unique cross-University Research Centre between the Universities of Birmingham and Nottingham aimed at investigating the mechanisms of cell communication in physiology and disease to develop innovative therapies for common conditions such as cardiovascular disease, diabetes or cancer. To achieve this goal, we bring together experts from multiple disciplines (Medicine, Biology, Chemistry, Physics, Maths and Computer Science) to advance our understanding of disease mechanisms and drug action using a highly innovative multidisciplinary approach.

These efforts are supported by dedicated, state-of-the-art facilities, including our COMPARE Advanced Imaging Facility, which are open to internal and external researchers from both academia and industry.

This session will feature some of the cutting-edge research from COMPARE, including both novel technology developments and their application to elucidate the mechanisms of GPCR signalling in physiology and disease.

Canadian research hubs: Université de Montréal, Université de Sherbrooke, McGill University

Chair: Stéphane Laporte

McGill University, Division of Endocrinology and Metabolism Department of Medicine, Montreal, Quebec, Canada

Dr. Stéphane Laporte, a professor of medicine at McGill University, is a globally recognized expert in the molecular pharmacology of GPCRs. His research has elucidated key mechanisms governing β-arrestin-mediated GPCR internalization and trafficking, utilizing pioneering microscopy and biophysical techniques. 

As a core member of a Quebec consortium on GPCR signaling, which includes collaborators from Université de Montréal, Université de Sherbrooke, and McGill University, he has been instrumental in advancing Bioluminescence Resonance Energy Transfer (BRET) approaches. Through the design of innovative sensors, his work, along with that of other consortium members, has enabled real-time studies of GPCR signaling and trafficking in live cells. Leveraging these tools alongside molecular modeling of GPCRs with international collaborators, Dr. Laporte has significantly contributed to our understanding of biased signaling and allosteric modulation, supporting discovery efforts targeting this critical receptor class.

This session will feature cutting-edge research on GPCR signaling by members of the consortium, including Dr. Terry Hébert from McGill University, with additional contributions from current trainees Dr. Étienne Billard and Dr. Ana Lilia Moreno Salinas from McGill University and Université de Sherbrooke, respectively. 

Alumnus of the consortium, Dr. Shane Wright, now at the Karolinska Institutet, will also present his work on biased receptor signaling in metabolic diseases. 

Given the central role of GPCR structural studies in advancing cell signaling and drug design, we will also hear from Dr. Louis-Philippe Picard, an early-career investigator who trained at the Université de Montréal and in Toronto, and recently recruited by Université de Sherbrooke. 

This session will underscore the growing expertise in GPCR research across Quebec and Canada, further enriching the landscape of discoveries in this field.

International Research Network (IRN) on GPCRs

Chairs:  

Ralf Jockers 

Institut Cochin (University of Paris, CNRS, Inserm)

Xavier ITURRIOZ

Laboratoire de Toxinologie Moléculaire et Biotechnologies (SIMOS, CEA, CNRS, Université Paris - Saclay)

Ralf Jockers has a long-term interest in GPCRs in endocrinology and metabolism including natural receptor variants and GPCR-associated protein complexes. Currently, he is INSERM Research director and group leader at the Institut Cochin (Paris, France). He is also director and French coordinator of the i-GPCRnet IRN. 

Xavier Iturrioz is an INSERM (Institut National de la Santé et de la Recherche Médicale) researcher, working in GPCR research and especially also on Apelin receptors for many years

The i-GPCRnet International Research Network (IRN)  was established in 2021 by the CNRS for a five-year period with the mission of advancing scientific research in the GPCR field. 

It is built on two strong pillars: the first is the robust French GPCR research community, and the second is the long-standing collaboration between French GDR members and internationally renowned laboratories, all of which have demonstrated the ability to unite research efforts within their respective countries.

The i-GPCRnet aims to address the largely unexplored question of how microenvironments affect GPCR function and the consequences of microenvironmental disruptions in common diseases such as cancer, metabolic disorders, and neurodegenerative conditions, as well as their treatments. 

The session will open with talks from three reknown researchers from the European GPCR community: Ralf Jockers, Stephen Hill, and Martin Lohse, who also act as coordinators of the i-GPCRnet.

The second part of the session will be moderated by Xavier Iturrioz, a representatives from the Early Career Scientist Committee of the i-GPCRnet. 

Chairs:

Jiafei Mao 

Institute of Chemistry, Chinese Academy of Sciences, Beijing, China

Sanduo Zheng 

National Institute of Biological Sciences, Beijing, China

Xiangyu Liu 

School of Pharmaceutical Sciences, Tsinghua University, Beijing, China

China is undoubtably unmissable in the GPCR research landscape. This session will be dedicated to young Chinese scientists working at GPCR frontiers. Their rising-star talks will showcase the diversity and originality of ongoing GPCR research activities in China, covering GPCR interactome, GPCR-transducer megacomplex, biased intracellular agonist, orphan receptors, opioid receptors and GPCR-inspired optogenetics.