Dr. GPCR Podcast

GPCRs and the Science Behind Pain and Recovery with Dr. Alex Serafini

1. Strategy: From Personal Pain to Scientific Purpose

Dr. Alex Serafini’s entry into science wasn’t typical. Born in California, raised in Silicon Valley, and initially eyeing finance, his trajectory took a sharp turn after struggling with unresolved, chronic pain following repeated surgeries for a pilonidal cyst.

"I wasn't able to get stronger pain meds because of the opioid epidemic," he recalls. That gap in care sparked a curiosity that became a career.

Driven by personal experience and a desire to innovate in pain management, Alex pursued a master's in pain research at Hopkins and later an MD-PhD at Mount Sinai. His early exposure to TRPV1 channels and peripheral pain mechanisms with Dr. Mike Caterina laid the foundation. But the deeper mission? Finding answers for patients society often overlooks. Pain became more than biology — it became a personal strategy.

“I started going through what I was going through… and that got me very interested in research.” — Alex Serafini

2. Decision-Making: Saying Yes to the Unorthodox Path

Serafini’s journey defied traditional checklists. He joined Mount Sinai through FlexMed — bypassing the MCAT — and was torn between a career in pharma and academia. At one point, he had a job offer at Roivant (a biotech firm known for repurposing shelved compounds), but a late-stage offer into an MD-PhD program — and parental “encouragement” — rerouted his path.

His approach to decision-making is pragmatic: follow impact, not orthodoxy. The decision to stay on as a postdoc in the same lab as his PhD — with Dr. Venetia Zachariou — wasn't the typical next step, but it allowed him to wrap up high-impact work and learn about PI-level grant writing, strategy, and lab management. In his words: “She let me run projects like a junior PI.”

“I didn’t need to chase new techniques — I needed to finish the science that mattered.” — Alex Serafini

3. Blind Spots: The Underestimated Role of RGS Proteins in Pain

Although not a self-proclaimed GPCR specialist, Serafini found himself repeatedly drawn to them, or more precisely, to RGS (Regulators of G protein Signaling) proteins. The lab’s work with RGS4 led to unexpected results: knockout mice spontaneously recovered from chronic pain after three weeks, an effect rarely observed.

He points out that GPCRs—especially orphan and CNS-associated ones—are often downplayed in pain research, with most focus on ionotropic targets like NAV1.8. But Serafini believes that’s a blind spot.

“We’re using outdated drugs. There are more elegant GPCR targets waiting to be explored.”

The lab’s unconventional in vivo-first strategies, combined with RNA-seq and behavioral analysis, revealed nuanced roles of RGS4, RGS9, and RGSZ — not just as modulators but as potential therapeutic linchpins.

“Half the time, in pain, what works in vivo doesn’t translate to clinic. We need new thinking.” — Alex Serafini

4. Failure & Frustration: From Pipettes to Pandemic Disruption

The road hasn’t been smooth. From struggling to grip mice in early animal studies to thesis delays during COVID-19, Serafini's journey is marked by grit. But it’s in these friction points that new insights emerged. The pandemic disruption, for instance, led him to BSL-3 labs to study persistent pain after SARS-CoV-2 infection, revealing novel immune-neuron signaling in DRGs.

He also opens up about the emotional and logistical toll of MD-PhD training. It’s an eight-year-plus haul with built-in uncertainty. However, with mentors who believed in him, especially those who shared administrative, grant-writing, and leadership skills early on, he found direction and resilience.

“She [Vanna] gave me a crash course in what it’s like to be a junior PI. That changed everything.” — Alex Serafini

5. Pivoting: Redefining the Pain Research Playbook

Looking ahead, Serafini’s vision is bold: build a lab that develops translational models of pain rooted in patient realities. He’s fascinated by transgenerational epigenetics — how parental pain, diet, or drug exposure can leave molecular fingerprints in offspring. He's equally focused on sex differences in pain processing and the failure of "one-size-fits-all" models in pharmacology.

His advice? Learn broadly. Stay close to patients. Collaborate relentlessly. And above all, don’t be afraid to start from the phenotype and work backwards to the mechanism. That top-down approach, though less common, could help pain research finally catch up with the complexity of real-world biology.

“Start from the end — from the clinic — and then build backwards.” — Alex Serafini

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Key Takeaway

Innovation in pain research won’t come from doing the same things better — it’ll come from flipping the script. Whether it’s challenging legacy targets, redefining preclinical models, or exploring the epigenetic inheritance of pain, Dr. Serafini urges the field to stay bold, patient-centered, and GPCR-aware.

Keyword Cloud

GPCR research community, Dr. GPCR ecosystem, GPCR drug discovery, GPCR podcast, GPCR data platform, GPCR training program, RGS4, chronic pain, epigenetics, translational models.

Summary created by AI

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About Alex Serafini

Alex was born and raised in the Bay Area and received his BS/MS Neuroscience from Johns Hopkins. His master's degree was in Dr. Michael Caterina's lab studying the role of PNS chloride transporters in neuropathic pain. Upon matriculating to Mount Sinai's MD/PhD program, he joined Dr. Venetia Zachariou's lab to study the effects of chronic pain and addiction/withdrawal on the mesocorticolimbic system, focusing on transcription factor and RGS protein maladaptations, behavioral RGS protein drug "screening", and the role of SARS-CoV-2 on CNS function and sensory hypersensitivity. He aspires to become a physician-scientist, with a focus on translational in vitro and in vivo model development for studying chronic pain and affective comorbidities. Other academic interests of his include studying pharmaceutical finance & healthcare administration and developing technologies that increase healthcare access. His non-academic interests include traveling, scouting out micro-breweries, and collecting beer cans.

Alex Serafini on the web

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