Dr. GPCR Podcast
Strategic Partners
Hacking GPCRs: Tools, Tech & Drug Discovery with Tom Sakmar & Ilana Kotliar
In this episode, host Dr. Yamina Berchiche reconnects with Dr. Tom Sakmar, Professor at Rockefeller University, and Dr. Ilana Kotliar, his former graduate student, to explore the development of powerful multiplex tools designed to map GPCR-RAMP interactions across the receptor superfamily. What began as a focused exploration into Family B GPCRs evolved into a comprehensive resource for the GPCR research community — bridging wet-lab experimentation, open-access tools, and computational biology.
1. A Long-Term Vision Realized
“We've done this work for the past 30 years.” – Tom Sakmar
Dr. Sakmar recounts how a fateful phone call from Bruce Merrifield decades ago inspired his lifelong focus on Family B GPCRs. That curiosity laid the foundation for a broader investigation into receptor activity-modifying proteins (RAMPs). The lab’s early partnership with students like Emily Lorenzen catalyzed a transition from single-receptor studies to multiplexed approaches, opening doors to high-throughput interaction mapping.
2. From Curiosity to Collaboration
“We decided to evaluate the multiplexing methods... and found this Luminex assay.” – Tom Sakmar
After exploring several screening techniques, the lab adopted the Luminex bead-based assay, which allowed simultaneous detection of multiple GPCR-RAMP interactions. This methodology was enhanced through collaboration with Jochen Schwenk’s lab at SciLifeLab in Karolinska. The result: a scalable platform to analyze hundreds of interactions with minimal sample usage.
3. A Rotation That Changed Everything
“I really love this project. I want to take it forward.” – Ilana Kotliar
Dr. Kotliar joined the Sakmar lab as a rotation student and immediately saw the project’s potential. She expanded the original Family B focus to encompass the entire GPCR superfamily, building a digital and physical toolkit to systematically investigate GPCR-RAMP biology. Her goal was ambitious: map the complete interactome and validate findings in both overexpression and native contexts.
4. Tools for the Community
“We have a library on Addgene... dual-epitope tagged GPCRs.” – Ilana Kotliar
The team developed two main assets:
A web interface to visualize antibody validations and GPCR-RAMP interactions.
A DUET-tagged GPCR library (220 constructs) available through Addgene, enabling labs to explore interactions with ease.
These tools are fully open to academic researchers, with wide applicability beyond just RAMPs — including scaffold proteins, disease markers, and heterodimerization partners.
5. Driving Impact through Open Science
“500+ requests have come in for these clones.” – Tom Sakmar
Dr. Sakmar highlights the vital role of Addgene in distributing the DUET library. The logistical lift was considerable — involving extensive 96-well plate work and documentation — but the team prioritized accessibility over proprietary restrictions. Their ethos: empower fellow scientists, not profit from them.
6. Beyond GPCR-RAMP: New Avenues
“What if your favorite scaffold protein interacts with GPCRs?” – Tom Sakmar
The constructs aren’t limited to RAMP interaction studies. They can be used to probe GPCR associations with any protein, from cytoskeletal scaffolds like 14-3-3 and P11 to disease-linked interactors. The system is modular and adaptable, opening doors for systems biology and context-specific interaction mapping.
7. A Diagnostic Future
“Autoantibodies targeting GPCRs might drive disease.” – Tom Sakmar
One especially exciting avenue is autoimmune and infectious diseases. The team envisions using these tools to detect GPCR autoantibodies, which are implicated in conditions like long COVID and Graves’ disease. Unlike blocking antibodies, some autoantibodies activate GPCRs, potentially driving pathophysiology — a paradigm-shifting concept in GPCR immunology.
8. From Many to One: De-Orphanization and Precision Focus
“You can use this system to de-orphanize receptors.” – Ilana Kotliar
While the toolkit enables broad interactome analysis, it’s also valuable for narrowing in on orphan GPCRs — receptors with unknown ligands or function. This could accelerate discovery of therapeutic targets by combining multiplex data with focused downstream assays. In Ilana’s words, it’s a powerful way to “go from many back to one.”
9. The Shift Toward Technology-Driven Biology
“Today’s students want to multiplex, miniaturize, and engineer tools.” – Tom Sakmar
Dr. Sakmar reflects on the generational shift in research culture. Instead of focusing on a single receptor, students now gravitate toward platforms, biosensors, and data-rich assays. The multiplex strategy aligns perfectly with this evolution, providing scalable approaches to biological discovery.
10. Global Collaboration and Computational Frontiers
“There is no science that ends at a national border.” – Tom Sakmar
The success of this project hinged on international collaboration and a multidisciplinary mindset. As the field advances, the computational layer — including AlphaFold and structural prediction tools — will play an increasingly pivotal role. This synergy of wet-lab, in silico, and community-driven resources promises a new era for GPCR systems biology.
Summary made with AI
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Key Takeaway
This episode is more than a conversation — it’s a masterclass in tool-driven discovery, community science, and the future of GPCR interaction mapping. If you’re working on GPCRs, this is your call to leverage these tools, ask new questions, and help unlock previously hidden layers of receptor biology.
Keyword Cloud
GPCR-RAMP interactions, multiplex assays, GPCR research community, Dr. GPCR ecosystem, GPCR data platform, GPCR autoantibodies, Addgene GPCR library, GPCR training program, GPCR drug discovery, GPCR online course
Summary created by AI
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About Tom Sakmar
Tom Sakmar is a physician-scientist and Rockefeller University professor dedicated to drug discovery and chemical biology research, mainly involving GPCRs. He and his artist/designer wife, Karina Åberg, have three teenage children.
Tom Sakmar on the web
About Ilana Kotliar
Ilana Kotliar is a 5th year graduate student in the lab of Dr. Thomas Sakmar at The Rockefeller University and just recently defended her PhD thesis. Ilana uses chemical biology-based methods to study the regulation and protein-protein interactions of GPCRs. Ilana’s research is multi-disciplinary and involves a close collaboration with the lab of proteomics expert Dr. Jochen Schwenk, located at The Science for Life Laboratory in Sweden. She is a recipient of the prestigious Women in Entrepreneurship Award, an NIH T32 Training Grant, and two Nicholson Fellowships. Outside of the lab, Ilana is a leader within her community, spearheading several outreach initiatives including a global mentoring initiative that matches graduate student mentors to PhD applicants. Ilana graduated Summa cum laude from Cornell University, where she studied Chemistry and Chemical Biology and was recognized as a Merrill Presidential Scholar.
Ilana Kotliar on the web
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