In this science-focused episode of the Dr. GPCR podcast, we meet Dr. Ian Chronis, a freshly minted PhD from the University of Michigan. While his academic roots started in classical history and ancient Greek, Ian’s curiosity pulled him toward chemistry, then pharmacology, and eventually into the complex world of GPCR signaling. His story is a testament to the power of staying open to change and following emerging scientific questions wherever they lead.

Ian’s doctoral work focused on two key GPCR systems: the well-characterized β2-adrenergic receptor and the lesser-known proton-sensing receptor GPR65. In the former, he explored how PKA phosphorylation modulates receptor interactions and discovered a regulatory role for 14-3-3 proteins. But it’s GPR65 — a receptor that constitutively internalizes and signals from acidic endosomes — that has captured Ian’s attention and become the centerpiece of his current research. Unlike classical GPCRs, GPR65 uses non-canonical internalization mechanisms, presenting new opportunities to uncover novel biology.

The receptor’s ability to signal within the tumor microenvironment and immune cells makes it an emerging drug target, especially in cancer immunotherapy. However, there are still major gaps: no selective ligands, little clarity on its internalization machinery, and limited tools to modulate its function. Ian’s wish list? A high-affinity agonist and antagonist to begin untangling these questions. Until then, he's carefully optimizing pH-based assays and preparing for next steps in a postdoctoral lab focused on more physiological and therapeutic systems.

Whether he’s decoding novel trafficking pathways or reflecting on career strategy, Ian brings a balanced perspective that’s both ambitious and grounded. His advice to peers? Attend talks outside your field, learn constantly, and surround yourself with people who make science sustainable. This episode is a must-listen for those navigating the intersection of curiosity, technical rigor, and translational potential in the GPCR research community.

Watch the video version of this podcast episode:

https://www.ecosystem.drgpcr.com/dr-gpcr-podcast/ep-164-with-dr.-ian-chronis

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