Triangle CERSI accelerates FDA response to complex, high-priority challenges

A few years ago, xylazine, a veterinary tranquilizer known colloquially as tranq, began showing up in the unregulated fentanyl supply. Its use became associated with necrotic wounds developing in people who use drugs, and there was scant research into how xylazine could influence opioid use. From 2020 to 2021, xylazine-positive overdose deaths spiked by 1,127% in the U.S. South.

Decision-makers hoping to mitigate this growing crisis needed data on xylazine’s effects on physiology — and they needed it fast.

Enter the Triangle Center of Excellence in Regulatory Science and Innovation, or Triangle CERSI, a multi-institution consortium launched by the Food and Drug Administration at UNC-Chapel Hill on Sept. 1, 2023, with additional support from Eshelman Innovation.

One week after that launch date, the FDA awarded a comprehensive Triangle CERSI xylazine grant to a group of Carolina researchers. They are led by Principal Investigator Zoe McElligott, associate professor in the UNC School of Medicine’s psychiatry and pharmacology departments.

“We assembled an Avengers-style team to tackle the xylazine problem,” says McElligott.

She and six Carolina colleagues are studying xylazine from a range of perspectives, including pharmacology, addiction-related behaviors, wound healing and more. The typical academic grant process moves slowly, McElligott says. “The CERSI grant allowed us to spring into action.”

The xylazine study received one of six initial grants. In September of 2024, the FDA funded five more research projects, bringing the award total to $11 million. The FDA will award the Triangle CERSI up to $50 million during its first five years. 

True partnership

Urgency is baked into the CERSI mission: to help the FDA keep up with today’s rapidly evolving science and technology.

“This system of CERSIs was established with the FDA recognizing that they can’t be an expert in everything, especially at the rate science is going, and that they need top academic partners to address critical gaps in knowledge,” says Triangle CERSI’s UNC Principal Investigator Paul Watkins, professor in UNC’s Eshelman School of Pharmacy, School of Medicine and Gillings School of Global Public Health. “The CERSIs have created a mechanism to rapidly fund close collaborations between FDA scientists and academics to address specific problems. It’s a true partnership.”

The newest in a network of five CERSIs, the Triangle CERSI is led by Carolina and Duke University, in partnership with North Carolina Central University, North Carolina State University and the Burroughs Wellcome Fund. The center leverages the breadth and depth of scientific expertise available across North Carolina’s Research Triangle to conduct research, disseminate knowledge, catalyze action among stakeholders and advance regulatory decision making. 

“The Triangle CERSI will equip the FDA with tools and methods to overcome the challenges of the 21st century drug and device development process in order to rapidly advance public health interests,” Susan Halabi, a Duke professor of biostatistics and bioinformatics and one of three Duke principal investigators, said when the Triangle CERSI launched.

The xylazine project is one of five Triangle CERSI projects addressing the opioid crisis. Four additional projects focus on how to analyze real-world data to improve cancer treatments, especially for ethnically and racially diverse populations. Two projects involve seeking input from patients on their experiences with treatments and clinical outcomes.

“We want to accelerate FDA’s access to emerging scientific approaches and solutions essential for faster, smarter and more efficient regulatory decision-making,” says Triangle CERSI Executive Director Christin Daniels, who is with Eshelman Innovation. “We accomplish this through a catalytic array of research, education and training initiatives that forge our scientific partnerships with the FDA.”

Remarkable discovery

The rapid-response research into xylazine is a great example of how the Triangle CERSI can make a difference. The Avengers-style team already made a remarkable discovery — that, in addition to its other targets, xylazine activates kappa opioid receptors similar to how fentanyl activates opioid receptors. This finding could hint at why withdrawal from fentanyl in combination with xylazine is so severe.

In March of 2024, one of the study’s researchers, Nabarun Dasgupta, presented the team’s early findings to the North Carolina General Assembly’s House Subcommittee on Substance Abuse. Dasgupta is senior scientist at the UNC Injury Prevention Research Center and an innovation fellow at the Gillings School.

“The ‘bench science’ results from this elite team could have practical implications for how first responders, wound care experts, harm reduction communities and clinics that provide medications for opioid use disorder adjust their approach to treatment as they deal with the influx of adulterants to fentanyl,” Daniels says.

“The Triangle CERSI, like Eshelman Innovation, is singularly focused on impact — channeling academic research to improve people’s lives,” says Eshelman Innovation Executive Director John Bamforth.

With multiple research projects underway and more on the horizon, the Triangle CERSI will positively impact the regulatory actions of the FDA and, thereby, benefit the people of North Carolina and the entire country.

CERSI projects are supported by the Food and Drug Administration (FDA) of the U.S. Department of Health and Human Services (HHS) as part of a financial assistance award, U01FD007857. The contents are those of the author(s) and do not necessarily represent the official views of, nor an endorsement, by FDA/HHS, or the U.S. Government.