By Jeff Kelley

In the world of drug development, university researchers play a critical role in creating promising new therapies. Under the leadership of new director Yan Zhang, Ph.D., the Virginia Commonwealth University Center for Drug Discovery is undergoing a major transformation — realigning its structure to mirror the industry-standard drug development pipeline and expanding to become a true VCU-wide hub for translational research.

Historically, the center operated without a formally integrated infrastructure. But Zhang has rebuilt the center to mimic the full continuum of drug development — from target discovery and molecular design to preclinical testing and potentially early-stage clinical trials.

“The idea is to follow the proven model used by pharmaceutical companies and to leverage the talent and infrastructure we already have here at VCU,” said Zhang, a professor in the Department of Medicinal Chemistry at the School of Pharmacy. The initiative is aimed at making VCU’s research more competitive for industry partnerships, federal funding and eventual approval by the Food and Drug Administration.

VCU's Center for Drug Discovery is one of 17 research institutes and centers supported by the Office of the Vice President for Research and Innovation. Representing some of the most cutting-edge investigations taking place in the world today, the institutes and centers conduct unique transdisciplinary collaborations to create new knowledge and groundbreaking discoveries.

Mimicking the drug development process

With their advanced laboratories and skilled academics, public universities like VCU are often the birthplace of new therapies; various studies estimate around 30 percent of new drugs originate in a university setting. The contributions are even higher when considering that many foundational molecules and mechanisms of drugs are discovered in academia.

At VCU, such intellectual property is protected by TechTransfer and Ventures, which helps license drug technologies to companies or facilitates forming startups to bring lifesaving treatments to market.

The most promising research is funded by federal grants and university endowments. Eventually, the work is either rolled into a startup or licensed by an established pharmaceutical company that can manage the clinical trials and, once approved, bring the drug to market. It takes years of development from drug discovery to commercialization.

Zhang’s effort at VCU includes reorganizing the Center for Drug Discovery’s nine core research facilities to match the sequence of drug discovery. He is also expanding faculty participation beyond the School of Pharmacy to include more researchers from medicine, dentistry, engineering, chemistry and other disciplines.

“Now, the center’s faculty covers the whole universe of drug development,” Zhang said.

The additional members have effectively doubled the size of the center’s team. Based on their skillsets and areas of interest, researchers are assigned to different points in the drug discovery process.

“There’s tremendous new potential in the Center for Drug Discovery under Yan’s leadership,” said Magdalena Morgan, Ph.D., director of licensing at TechTransfer and Ventures. “We’re excited to see researchers from across the university coming together at the center, and we’re working to ensure they have the support and guidance needed to move promising compounds toward commercialization. Many of these scientists are brilliant in the lab but need help bridging the gap to industry — that’s where we come in.”

Leading the commercialization pipeline

Zhang points to three promising therapies that are moving closer to clinical trials for treating:

Sickle cell disease: Martin Safo, Ph.D., a professor in the Department of Medicinal Chemistry, has spent his career focused on research aimed at advancing treatment for sickle cell disease, which predominantly affects Black patients. His team is creating an “anti-sickling” drug agent to transform the disease into a manageable chronic condition — or serve as a functional cure. The startup he co-founded, IllExcor Therapeutics, is nearing trials of lead drug ILX002, designed to bind to hemoglobin and directly block the sickling and clumping of red blood cells. Safo and Illexcor hope to begin the first-in-human trials soon.

Opioid addiction: Zhang’s own work centers on developing a new class of drugs to combat fentanyl’s toxicity and improve overdose and addiction treatment. The approach targets mu opioid receptors that are among a family of critical proteins that modulate pain. However, a major side effect from applying mu opioid receptor antagonists — one of which is fentanyl — are abuse, addiction and overdose. Zhang’s approach is developing an agent to block fentanyl’s ability to attach itself to the opioid receptors, offering a potential breakthrough in opioid crisis intervention. His work is funded by the National Institute on Drug Abuse.

Alzheimer’s and related dementias: Shijun Zhang, Ph.D., professor and graduate program director in the Department of Medicinal Chemistry, is developing drug candidates that can block the immune system’s NLRP3 inflammasome, which he calls “the first line of defense whenever our body detects a pathogenic invasion or dangers like a bacteria or virus.” When overactivated, NLRP3 has been linked to Alzheimer’s and related dementias, as well as other neurodegenerative and inflammatory disorders like arthritis. That makes it a promising target for new dementia drugs.

TechTransfer and Ventures is working closely with the center to protect emerging intellectual property and guide researchers in preparing their compounds for potential licensing. The center plans to launch a pilot grant program this summer to support early-stage drug development and will co-host workshops on commercialization, biostatistics and FDA readiness.

“We want to not only build out the infrastructure but also help investigators move their work forward,” Yan Zhang said. “This is about creating a true universitywide engine for therapeutic innovation.”