Ecosystem
Dr. GPCR Podcast
When to Walk, When to Run: Lessons from the GPCR Trenches with Dr. Ben Clements
When to Walk, When to Run: Lessons from the GPCR Trenches with Dr. Ben Clements
1. The Power of Inclusion in the GPCR Field
This episode kicks off with a celebration of early-career scientists. Host Dr. Yamina Berchiche emphasizes the importance of diverse voices in the GPCR community:
“It’s been a very difficult path to get more early-career scientists on the podcast. But it’s important to make your voice heard.”
Benjamin Clements, a postdoctoral fellow at the University of Michigan, joins the conversation as a rising voice in GPCR pharmacology. His journey highlights the transition from general drug development to a deep dive into G protein-coupled receptors.
2. From Aspirations to Application: Ben’s Path into Science
Ben shares his winding yet deliberate entry into science. Initially driven by a general passion for biology and a childhood dream of being an astronaut, he began with intestinal choline transport research at UNC. The realization that basic science could impact real patients was transformative.
“It’s not just raw science — this can help someone at the end of the day.” – Ben Clements
His pivot into neuroscience and pharmacology during grad school at the University of Minnesota laid the groundwork for his current work in GPCR pharmacology.
3. GPCRs and the Opioid Crisis: A New Pharmacological Frontier
Now at the University of Michigan, Ben focuses on positive allosteric modulators (PAMs) targeting opioid receptors. The goal: maximize analgesia while minimizing side effects.
“We’re enhancing the powerful pain-relieving effects of opioids while limiting respiratory depression, constipation, and abuse liability.”
He is particularly excited by the novel application of PAMs in chronic and neuropathic pain models, including the neuroma model, which is typically opioid-insensitive.
4. Allosteric Modulation: The New Frontier of GPCR Drug Discovery
Ben reflects on the emerging potential of allosteric modulation in GPCRs — a field that has lagged behind ion channels in clinical applications.
“Allosteric modulation in GPCRs is so novel and so exciting. There’s so much availability, so much we don’t know yet.”
By working with distinct chemical scaffolds like thiazolidines and xanthinediones, Ben is helping define how structurally different PAMs may act on similar receptor sites.
5. Scientific Rigor: The Value of ‘Old School’ Pharmacology
Despite the availability of modern tools, Ben stresses the enduring value of classical methods like GTPγS assays, radioligand binding, and basic PK/PD models.
“It doesn’t matter how many cool, fun tools you have. If you don’t understand the math that underlies an allosteric modulator, you won’t understand what’s happening.”
This mindset keeps his science grounded, reproducible, and rooted in fundamentals.
6. Mentorship, Team Culture, and the Joy of Science
Science is serious work, but Ben believes fun and collaboration fuel great outcomes. At Michigan, his lab balances rigor with light-hearted engagement — like daily squirrel trivia on their whiteboard.
“Science is fun. We produce great data, but we also joke around. That’s how we work best.”
Strong mentorship, open communication, and peer learning — especially from undergraduate trainees — shape his development as both a scientist and future educator.
7. Translating Discovery into Therapy: Bench to Bedside Vision
Ben’s work seeks to merge in vitro mechanistic data with in vivo efficacy, guiding medicinal chemists toward creating druggable PAMs.
“The goal is to smash all the amazing biology together and make a drug.”
Using site-directed mutagenesis and pharmacological synergy assays, his team aims to understand how and where these compounds interact with the receptor, paving the way for structure-based drug design.
8. Structural Biology Roadblocks: The Cryo-EM Challenge
One bottleneck in Ben’s work is visualizing binding sites of PAMs via cryo-EM, due to low compound potency and membrane-embedded binding pockets.
“Our compounds don’t bind well enough to be seen clearly. That’s a real challenge with allosterics.”
Still, by collaborating with structural biology teams and combining cryo-EM with NMR, his lab is narrowing down potential binding regions.
9. Lessons in Confidence, Collaboration, and Aha Moments
From asserting himself as an undergrad to mastering unique techniques in grad school, Ben has accumulated key “aha” moments that shaped his confidence:
Standing up to big names when safety was compromised.
Realizing his technical skills were indispensable to the team.
Discovering breakthrough results in neuroma pain models via a spontaneous collaboration.
“We found something incredible — a tenfold shift in the methadone dose-response with our PAM.”
10. Advice for Junior Scientists: Read, Rest, Run
Ben closes with wisdom for early-career researchers:
“Academia is about knowing when to walk and when to run.” – Advice from Kelsey Flepsen
He advocates:
Reading one paper a day.
Taking care of yourself when possible.
Pushing hard when deadlines or breakthroughs demand it.
“Your brain’s not a machine. Let it rest. That’s when the best ideas come — in the shower or on a walk.”
Summary made with AI
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Key Takeaway
Episode 166 with Ben Clements is a deep dive into the pharmacological potential of GPCRs, the power of mentorship, and the mindset required to thrive in science. With clarity, curiosity, and a collaborative spirit, Ben reminds us that impactful science isn’t just about technology — it’s about people, persistence, and timing.
“Science is all about knowing when to walk and knowing when to run.”
Keyword Cloud
GPCR research community, Dr. GPCR ecosystem, GPCR online course, GPCR scientist network, GPCR drug discovery, GPCR training program, G protein-coupled receptors, GPCR podcast, GPCR webinar series, GPCR data platform
Summary created by AI
About Ben Clements
Dr. Ben M Clements is a behavioral pharmacologist who uses in vitro and in vivo models to discover and characterize novel treatments for chronic pain and opioid use disorder. He received his Ph.D. in Pharmaceutics from the University of Minnesota in 2022, studying the pharmacokinetics and pharmacodynamics of NMDA receptor antagonists. At the University of Michigan, Ben focuses on determining the mechanisms of action of a series of positive allosteric modulators of the mu-opioid receptor. This project involves molecular pharmacology in cell models to determine binding sites and mechanisms of allostery, as well as efficacy studies in mouse and rat models of acute and chronic pain.
Dr. Clements' work is primarily focused on translational developments of small molecule therapeutics, and intends to apply these ideas to an independent academic laboratory. In addition, he plans to continue studying how neuromodulators, both exogenous and endogenous, can influence cellular activity, physiological behaviors, and human health.
Ben Clements on the web
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