Biosafety Month Researcher Spotlight

USC Researcher Spotlight: Dr. Zhen Zhao

Celebrating Biosafety Month 2025

In honor of Biosafety Month at USC, Environmental Health & Safety (EH&S) is proud to spotlight the work of Dr. Zhen Zhao, a leading researcher in the Department of Physiology & Neuroscience at the Keck School of Medicine of USC. Dr. Zhao’s lab is tackling some of the most pressing questions in biomedical science, particularly how neurotropic viruses impact our nervous system, while maintaining a strong commitment to biosafety.

Understanding the Central Nervous System’s Vulnerability to Infection

Despite the central nervous system’s (CNS) having immune privilege, it remains susceptible to severe infections and chronic inflammation. Dr. Zhao’s lab investigates how neurotropic viruses affect our CNS and contribute to conditions like meningitis and encephalitis, which not only cause high fatality rates, but also result in disabilities and long-term sequelae including Encephalomyelitis and Guillain–Barré syndrome among survivors.

“As a lab focused on brain health and diseases, we are very interested in understanding the impact of neurotropic viruses such as Zika virus and Herpes simplex virus (HSV-1) on our nervous system, as well as emerging pathogens that have strong neurological sequelae, such as SARS-CoV-2,” says Dr. Zhao.

Collaborative Research Driving Breakthroughs

Key Accomplishments

• Zika Virus: The lab discovered that Zika’s capsid protein suppresses host microRNA production by targeting the Dicer enzyme and host microRNA machinery. Their recent work on this subject has further identified that Dicer also produces small RNAs from the Zika viral genome, which have strong anti-viral effects. The lab’s work, published in Cell Stem Cell, received R01 funding from the National Institutes of Health (NIH) and National Institute of Neurological Disorders and Stroke (NINDS).
• HSV-1: Their work, published on Nature Aging, has revealed that HSV-1 breaks down tissue barriers in the brain organoids and activates native immune cells (like microglia). Inhibiting the cGAS-STING innate immune pathway mitigates neuroinflammation, which was further tested in the Alzheimer’s mouse model, and substantially reduced the amyloid pathology, neuroinflammation and neurodegeneration.

“This work was published on Nature Aging. Based on that, we are now developing new series of STING inhibitors with the Mann School of Pharmacy,” says Dr. Zhao.

• SARS-CoV-2: In collaboration with USC’s Institutional Biosafety Committee (IBC), veterinarians, and the Hastings and Wright BSL-3 High Containment laboratory at USC, Dr. Zhao’s team developed a long-COVID mouse model. The work showed that even mild infections led to neurological complications in mice, including brain tissue barrier breakdown, activation of microglia and macrophages, and behavioral changes leading to alterations in sensorimeter functions such as increased anxiety and stress.

Biosafety at the Core

Dr. Zhao emphasizes that biosafety is a top priority in his lab:

“Biosafety is definitely number one priority for us, particularly when we work with infectious agents and chemicals on a daily basis… USC has a wonderful biosafety team and IBC committee, who work tirelessly to support our research community. They help us tremendously on each of the projects, and provide us clear and practical guidelines in dealing with pathogens or chemicals. We could [not] have done these cool studies without their hard work.” says Dr. Zhao.

As a new member of USC’s Institutional Biosafety Committee, Dr. Zhao has gained firsthand insight into the protocol review process and praises the committee’s teamwork, transparency, and efficiency.

Publications

Dr. Zhao’s work has been widely published in leading journals, including:

• Journal of Medical Virology: Studies on SARS-CoV-2 and HSV-1
•  Nature Aging: cGAS-STING pathway’s role in Alzheimer’s
• Cell Stem Cell: Zika virus’s impact on neurogenesis