Big NIH grants enable Zhang to study common threats to the brain and heart

By Patrick L. Kennedy

Professor Katherine Yanhang Zhang (ME, BME, MSE) had already established herself as an expert in the mechanics and mechanobiology of arterial tissue. But, this year, with the help of two large grants from the National Institutes of Health, she’s extended that expertise to the study of brain as well as heart arteries, aiming to discover origins and portents of Alzheimer’s disease and a life-threatening condition known as aortic dissection.

Katherine Yanhang Zhang (ME, BME, MSE)

“The overarching goal for both grants is to have early detection and intervention of these diseases,” says Zhang. “It’s exciting that we have the tools now for looking at these very sophisticated mechanical aspects of the arteries, and can combine that with our understanding of microstructure and the clinical data that’s out there.”

Alzheimer’s disease is the most common cause of dementia, afflicting nearly 6 million Americans, and the sixth most common cause of death in the U.S. A growing body of evidence points to cerebrovascular dysfunction—problems in the arteries that are critical for proper function of the brain—as a culprit.

Zhang’s goal, with a five-year NIH R01 research grant totaling $3.9 million, is to unravel the connection between cerebrovascular integrity and brain health, with a focus on the cerebral arteries.

“We have some preliminary results showing that cerebral arteries become stiffened and lose their elasticity in Alzheimer’s disease,” Zhang says. “We want to understand the changes in the biomechanics and microstructures of the cerebral vessels and how that affects the pathology in the brain. It’s a challenging, chicken-or-egg problem.”

In the long term, Zhang hopes her work will result in diagnostic tests that would catch warning signs in the arteries before Alzheimer’s progresses. “It’s great to have access to donor tissue samples from the BU Alzheimer’s Disease Center, so we can establish these connections,” Zhang says. “But it would be great to see this without having to look at the postmortem tissue.”

Irving Bigio (BME, ECE, Physics, Medicine)

Zhang’s co-PIs in the study are Joseph Zaia and Thor Stein, professors at the BU Chobanian & Avedisian School of Medicine. Professor Irving Bigio (BME, ECE, Physics, Medicine) collaborates with Zhang on high-resolution imaging and quantitative assessment of vessel structural proteins and cells.

Zhang is the sole PI on the second of the two NIH grants she’s received this year. This $2.2 million R01 grant focuses on aortic dissection, which is one of the top 20 causes of death in the U.S. As in the Alzheimer’s study, Zhang has zeroed in on structural defects in the arteries as a potential cause for the disease. But, where her concern there is on cerebral arteries stiffening, here the issue is when the aorta (the largest blood vessel that transports blood from the heart to the rest of your body) develops layer separations or local defects in the aortic wall.

Zhang is working on this grant with a collaborator, Andy Yun, a Harvard Medical School professor and research scholar at Massachusetts General Hospital.

“A lot of people have the risk factors for aortic dissection, a relatively rare disease and often challenging to detect, but when it happens, it’s really, really bad,” says Zhang. “The knowledge we gain from this research should provide insights into the biomechanical markers for aortic dissection, and that will be useful for early diagnosis and treatment.”

Top: Multiphoton image of a human cerebral artery showing the proteins elastin (green) and collagen (red) in the arterial wall. Courtesy of Katherine Zhang