GPCR Pathway & Function Focus Day

Tuesday, March 22 2022 | 9.30 AM - 4.30 PM

9:30 am Registration & Morning Coffee Networking

9:50 am Chair’s Opening Remarks

  • Scott Prosser Professor of Biophysical Chemistry, University of Toronto

Leveraging GPCR Signaling Pathway Cross-Talk to Open up a Druggable Paradigm

10:00 am Variation in GPCR Signaling: Implications for Drug Discovery

  • M. Madan Babu Chair of Biological Data Science, St Jude Children’s Research Hospital


  • Leveraging data from diverse species to infer selectivity determinants of GPCR-G protein binding, which is critical to elicit the right intracellular response
  • Utilizing data on completely sequenced genomes of over 60,000 individuals from the human population to gain insights into natural receptor variation, which can result in variable drug response
  • Studying transcriptome data from over 30 different tissues in humans, one could begin to understand how alternative splicing creates diversity in GPCR signaling components, which may contribute to tissue-specific differences in receptor signaling
  • Understanding variation at these different dimensions, i.e., across different species, among different individuals of a species, and between tissues of a species, can provide a rich source of new hypotheses with implications for personalized medicine, drug development and understanding basic receptor biology


10:30 am Multiplexed Approaches to Interrogate Complex Disease Profiles


  • Developing treatments for complex diseases requires understanding the complexity of receptor and signaling pathways
  • Multiplex GPCR activity assays enable interrogation of ligand-target relationships across multiple targets and signaling modalities
  • Known compounds have unknown activity across mutiplex receptors, pathways, and signaling modalities useful for further drug development

11:00 am Targeting CXCR4-B2AR Heteromers in Cancer: Assays to Interrogate Heteromer Function


  • Introduce the technology used to identify GPCR heteromers to generate a database of interacting partners, as well as the selection of our lead targets in cancer
  • Share our strategy for in situ validation of CXCR4-B2AR targets
  • Discussion of in vitro validation of CXCR4-B2AR heteromer function by utilizing a variety of assay systems

11:30 am Morning Networking Break

12:00 pm Panel Discussion: Biased Signaling: From Pharmacology to Physiology


GPCR signaling can be activated in a ‘biased’ response, via G proteins or β-arrestins with distinct biochemical and physiological actions from each other. The current field however requires further clarity to evaluate biased signaling from pharmacology to physiology for the benefit of discovering biologically relevant GPCR targets. From determining bias specificity to rationally designing biased agonists, we will explore the challenges and future perspectives of biased signaling.

  • What determines bias specificity and understanding its importance to hit multiple GPCRs and signaling pathways?
  • How to rationally design biased agonists and overcome the pitfalls of over-expression systems for improved tissue specificity and biological relevance?
  • How do you quantify bias signaling for the future of GPCR-targeted drug discovery?

1:00 pm Networking Lunch

Unlocking Allosteric Modulation to Delineate GPCR Function & Regulation

2:00 pm Novel Pharmacology Approaches to GPCR Allosteric Modulation


  • Allosteric modulation of GPCRs is a promising approach for drug discovery
  • The structural biology revolution has illuminated the basis for GPCR allosteric modulation by small molecules
  • Describe the pharmacological and structural mechanisms of novel Class B GPCR allosteric modulators
  • Discuss if current pharmacology models are sufficient to describe GPCR allosteric modulation

2:30 pm Computational Protocols for Prediction of GPCR Allosteric Sites


  • Probe confined dynamic mapping protocols for allosteric site prediction
  • Case studies for mapping extracellular, intracellular and interface allosteric sites
  • Experimental validation of in silico protocols

3:00 pm Afternoon Networking Break

Unravelling Mechanisms of Adhesion Receptor Signaling to Enhance GPCR Pharmacology

3:30 pm Mechanism of Adhesion GPCR Activation

  • Gregory Tall Associate Professor , University of Michigan Medical School


  • Tethered agonist mechanism
  • Adhesion GPCR probe discovery
  • Shear force activation of adhesion GPCR – GPR56 in hemostasis

4:00 pm How to Wake Up Giants – The Signal Transduction of Adhesion GPCRs


  • Mechanisms of signal integration and transduction via large N termini
  • Characterizing the structural and functional variability of adhesion GPCRs
  • The cis- and trans-signaling: A unique feature of adhesion GPCRs

4:30 pm Chair’s Closing Remarks & End of Pre-Conference Focus Day

  • Scott Prosser Professor of Biophysical Chemistry, University of Toronto