VCU news

By Jeff Kelley

An alarm inside the body’s immune system could be the key to unlocking new treatments for Alzheimer’s disease, related dementias and other devastating diseases — and Shijun Zhang, Ph.D., is determined to silence it.

As a professor and graduate program director in the Department of Medicinal Chemistry at Virginia Commonwealth University’s School of Pharmacy, Zhang is pioneering drug discovery research focused on an essential component of the immune system – the NLRP3 inflammasome — which he calls “the first line of defense whenever our body detects a pathogenic invasion or dangers like a bacteria or virus.”

“There is growing evidence that dysregulation of the NLRP3 pathway contributes to numerous diseases, which is why both academia and pharmaceutical companies are actively pursuing ways to modulate it,” Zhang said.

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 drug treatments.

“Our research seeks to regulate the NLRP3 immune response to slow disease progression,” Zhang said.

He is leading one of five faculty research projects to receive new support from VCU TechTransfer and Ventures’ Commercialization Fund awards, a twice-yearly round of funding designed to bring VCU projects to a more mature stage of development in order to improve their chances of being licensed and brought to market.

To treat Alzheimer’s and related dementias, Zhang and his team, including research assistant professor Yiming Xu, Ph.D., have in recent years developed what they believe are promising candidate compounds to block NLRP3, called NLRP3 inhibitors. In early testing, the lead compounds bind differently to NLRP3 compared with existing drugs, and they reduce inflammation. They also can be taken orally versus intravenously.

Zhang is collaborating with researchers at Massachusetts General Hospital and Harvard Medical School, and in addition to backing from the VCU Commercialization Fund, he has an active National Institutes of Health grant. He hopes to begin investigational new drug-enabling studies within the next two years.

Zhang’s work began when a physician-scientist at VCU approached him to develop a small molecule targeting the inflammasome for treating acute myocardial infarction (a heart attack). Over time, Zhang expanded the project’s scope to focus on neurodegenerative disorders.

“This is one of our major projects, but overall, our lab is dedicated to developing small-molecule therapies for neurodegenerative and inflammatory disorders,” Zhang said.

‘The spirit of curiosity’

Srirama Rao, Ph.D., VCU vice president for research and innovation, said the five faculty projects receiving new Commercialization Fund awards reflect “the spirit of curiosity and determination that propel our university research forward.”

“We congratulate these inventors and hope this funding accelerates the research and development of their discoveries leading to technology transfer, commercialization and ultimately addressing societal needs,” Rao said. “I hope the ability to fund and support translational research within our schools and colleges will lead to the development of new intellectual property and also help us continue to attract remarkable talent to VCU.”

VCU closed 2024 with its most successful research year to date. The university and its adjacent academic medical center eclipsed $500 million in sponsored funding for the first time, saw international recognition for numerous faculty researchers and was ranked as a Top 50 public research university by the National Science Foundation.

“Each of the inventors we chose works in a different field, yet they are connected by a single thread: They are building on a discovery that has a market need, are backed by strong team, are aware of the risks and understand how to overcome them, and they have a clear timeline to bring their inventions to the marketplace,” said Ivelina Metcheva, Ph.D., assistant vice president of innovation at VCU TechTransfer and Ventures. “These awards reflect our commitment to advancing transformative discoveries and reinforcing VCU’s mission as a nationally recognized public research university dedicated to serving the greater good.”

Additional Commercialization Fund awards

Here are summaries of the four additional VCU faculty-led projects that received awards in the latest funding cycle:

Project: Tiny but mighty antennas.

Fund recipient: Supriyo Bandyopadhyay, Ph.D., Commonwealth Professor, Department of Electrical and Computer Engineering, College of Engineering.

With a portfolio of antennas and nanomagnetic devices, Bandyopadhyay has developed a groundbreaking nano-antenna that is tiny yet highly efficient, thanks to advanced quantum materials called TIs, or topological insulators. Unlike traditional antennas, which must be large to function effectively, the professor’s new antenna operates efficiently even at extremely small scales. It can also steer its signal in different directions without needing bulky equipment, making it a breakthrough for wireless communication.

Bandyopadhyay’s technology has market use in places where tiny, powerful antennas are essential: medical implants that require wireless communication from inside the body, stealth and defense technology, and future wireless telecommunications. His efforts may address a size vs. efficiency problem – typically the smaller the antenna, the less powerful it is – and remove the need for batteries in medical implants.

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Project: A new approach to Lyme disease vaccination.

Fund recipient: Richard Marconi, Ph.D., professor, Department of Microbiology and Immunology, School of Medicine.

Marconi has for years chased treatment for Lyme disease – and conquered it in dogs, inventing the canine vaccine that has been marketed by Zoetis since 2016. He has since turned his attention to humans, focusing on the same vaccine technology behind the canine one: chimerotopes.

These custom-designed proteins are made by combining important parts of multiple Lyme disease bacteria proteins. This approach helps trigger a stronger and more effective immune response to protect people from infection.

Lyme disease is the most common tick-borne illness in the U.S., Canada, Europe and Asia. It can be difficult to diagnose early because symptoms are often vague. If left untreated, Lyme can lead to serious long-term health problems, including nervous system issues, heart problems and joint pain.

There is no Lyme disease vaccine for humans; a previous one was discontinued due to public concerns, so a new and improved vaccine is needed. And by preventing the disease instead of merely treating it, Marconi’s vaccine could improve millions of lives and help control a growing public health problem.

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Project: Powering the future of precision medicine.

Fund recipients: Jinze Liu, Ph.D., professor, Department of Biostatistics, School of Public Health, and member, Massey Comprehensive Cancer Center;  Kevin Byrd, D.D.S., Ph.D., assistant professor of oral and craniofacial molecular biology, School of Dentistry, and member, Massey Comprehensive Cancer Center.

Treatment strategies are shifting away from the one-size-fits-all approach, instead tailoring therapies based on individual patient biology — called precision medicine.

Developed by Liu and Byrd, Astrograph is a software tool that uses artificial intelligence to interpret high-resolution images of tissues, identifying cell types, molecular properties and spatial interactions that were previously impossible to analyze with such depth and accuracy.

The inventors say it could revolutionize how scientists and doctors analyze the spatial organization of human cells — an essential step toward advancing precision medicine.

Astrograph accelerates the push toward precision medicine by providing detailed spatial cell analysis — improving diagnostics, disease monitoring and drug development. Beyond pharmaceutical companies and medical researchers, Liu and Byrd say, the technology has broad applications for government and regulatory agencies, contract research organizations and clinical settings. They say analysis of a cell’s spatial organization is a critical factor in understanding disease mechanisms and therapeutic responses.

Astrograph’s AI-powered spatial biology data and understanding of medical imaging “has the potential to become a foundational tool for advancing precision diagnostics and translational medicine,” Liu said.

The inventors are focused on scaling Astrograph for broader clinical and research adoption, making high-resolution spatial analysis accessible across biomedical fields.

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Project: A faster, easier way to detect liver disease.

Fund recipients: Amanda Elswick Gentry, Ph.D., assistant professor, Department of Psychiatry, School of Medicine; Christopher Ehrhardt, Ph.D., professor, Department of Forensic Science, College of Humanities and Sciences.

Gentry leads a team developing a new blood test to quickly detect liver inflammation and assess its severity without the need for painful biopsies or complicated lab tests. The test works by analyzing the natural glow (autofluorescence) that certain cells give off when exposed to light.

By measuring this glow in specific color ranges, doctors might be able to determine whether a patient has metabolic dysfunction-associated steatohepatitis— a serious form of fatty liver disease — and how advanced it is.

Current methods for diagnosing MASH and metabolic dysfunction-associated steatotic liver disease (MASLD) are slow, expensive and often require painful liver biopsies or imaging techniques that involve injecting dyes. Other lab tests, like mass spectrometry or antibody-based assays, can be complex and difficult to use in everyday clinical settings.

Unlike traditional methods, Gentry’s test does not require adding any dyes or chemicals to the sample. It uses widely available laboratory equipment (flow cytometers), can process a sample in under five minutes and works even on stored or frozen samples — meaning doctors and researchers can quickly and noninvasively track liver health through these novel biosignatures.