The number of people in Taiwan with cardiovascular diseases has increased throughout the past decade, with 79% originating in atherosclerotic cardiovascular disease (ASCVD), which now kills more people than cancer. The current treatment approach focuses on reducing the deposition of blood lipids on the vascular walls in order to lower the risk of coronary artery embolism.

Professor Jeng-Jiann Chiu, winner of the 67th Ministry of Education Academic Award, National Health Research Institutes Distinguished Investigator, and Chair Professor at Taipei Medical University College of Medical Science and Technology, has extended his research to places where ASCVD more easily develops, such as arterial bifurcations and curvatures, where blood flows more slowly and lipids accumulate more easily to form plaques. He hopes that by integrating interdisciplinary perspectives and cutting-edge technology he can produce breakthroughs in preventing diseases and promoting health.

What is the connection between ASCVD and fluid mechanics?

ASCVD is a common cardiovascular disease that arises when lipids on the arterial wall accumulate and lead to chronic inflammation, causing blood vessel narrowing and fibrosis. If left untreated, ASCVD could cause a myocardial infarction or stroke.

From the perspective of biomedical science, lipids are undoubtedly one of the main causes of arteriosclerosis. But hemodynamics offers a different perspective: at vascular bifurcations, blood produces disturbed flow, and much as how a river bend accumulates silt, this is intimately connected to the development of ASCVD. It takes a researcher well-versed in fluid mechanics to approach ASCVD from this perspective and Professor Chiu is an interdisciplinary expert in biomedical science and engineering, as mentioned above.

“Back when Taiwan was developing fighter jets and established the Department of Aeronautics and Astronautics, National Cheng Kung University, I got in on a National Chung-Shan Institute of Science and Technology Scholarship, with a guaranteed position on graduation at the National Chung-Shan Institute of Science and Technology.” Professor Chiu’s PhD dissertation calculated fluid mechanics, with applications ranging from aeronautical engineering to weather forecasting.

He further explains that fluid mechanics can be broadly divided into Experimental Fluid Dynamics and Computational Fluid Dynamics. The former uses experimental setups to simulate the operation of aircraft or missiles in the air or the conditions in an engine combustion chamber; the latter relies on mathematical models and computer simulations to study fluid motion without conducting experiments. “My research falls into the latter category, allowing me to explore the hemodynamics that are so closely related to human health.”

Hemodynamics, as the name suggests, is the study of blood flow within blood vessels. For example, the values returned when we measure blood pressure fall under the scope of hemodynamics; in other words, these seemingly abstract concepts actually impact our health every day.

“The vascular system is one of the most complex and extensive organ networks in the human body. Blood vessels are elastic, contracting and relaxing with each heartbeat, and feature a multiple branching structure. This, combined with the presence of various types of blood cells, makes the vascular system a highly complex fluid system. These diverse physical properties make the calculations extremely challenging, yet deeply connected to life itself,” says Professor Chiu, explaining why he became interested in hemodynamics. He decisively shifted from aeronautics to biomedical science, starting a completely new avenue of research from scratch.

Integrating fluid mechanics and biomedical science to open a new perspective on pathology

“My interdisciplinary background gave me two major advantages,” Professor Chiu points out. First, it enhanced his professional communication skills, allowing him to quickly understand ideas from researchers in different fields. Second, with his diverse thinking, he could deeply explore disease mechanisms from multiple angles.

He cites his research team’s 2023 findings published in the top-tier European Heart Journal as an example: “We discovered that the phosphorylation of vinculin (VCL) is due in part to disturbed blood flow. When turbulent blood flow occurs at vascular bifurcations, it alters the structure of vinculin, affecting cell permeability. This makes it easier for substances like lipids and white blood cells to accumulate on the vascular walls, accelerating the progression of arteriosclerosis.”

Simply put, vinculin is a protein that helps maintain the stability of a cell’s internal structure, akin to the steel reinforcement in a bridge that provides solid support. When the bridge (blood vessel) is damaged (disturbed flow), the steel reinforcement (vinculin) deforms (phosphorylation), leading to cracks and damage (atherosclerosis) in the bridge (blood vessel). This “mechanics + biology” way of thinking grants researchers a more comprehensive understanding of pathological mechanisms.

Notably, the innovation of this study lies in its integration of diverse research methods. For example, the team designed genetically modified animals to observe the effects of vinculin function loss, while also collecting patient samples to analyze the impact of medication on protein function. This research promises to enable serum testing to replace the current diagnostic methods of angiography and ultrasound, thereby creating a new diagnostic model for arteriosclerosis.

Considering the greatest challenge in his more than thirty years of biomedical research.

“As a scientific researcher, even with pioneering ideas, without the appropriate supporting technology, these ideas are hard to realize,” Professor Chiu says. His experiences over the years have made him deeply aware that, in order to achieve breakthroughs in biomedical research, innovative thinking and technology must complement each other.

He cites single-cell studies as an example, pointing out that, in the past, precise observation at the single-cell level was impossible. But recently, in collaboration with the Chinese University of Hong Kong, they used single-cell analysis to discover that the SOX4 transcription factor, under the influence of hyperlipidemia and oscillatory blood flow, facilitates abnormal changes in vascular endothelial cells, exacerbating atherosclerosis. This type of research would have been unimaginable twenty years ago.

“We also independently developed the world’s first high-throughput drug screening platform, specifically for studying the mechanisms by which hemodynamics facilitates atherosclerosis. This achievement is thanks to the development of DNA microarray technology, allowing us to complete large-scale drug screenings in a short amount of time, significantly improving research efficiency,” Professor Chiu adds. This research screened 125,000 compounds from Academia Sinica chemical drug databases and ultimately discovered the key molecule, KU-55933, that can inhibit endothelial cell proliferation and inflammation caused by disturbed blood flow, effectively reducing the incidence of atherosclerosis.

He proudly says, “KU-55933 was originally an Ataxia Telangiectasia Mutated Kinase inhibitor, which could induce apoptosis in cancer cells. But through our innovative screening method that integrates chemical and physical properties, we were the first to discover its potential application in arteriosclerosis. This breakthrough was not just a technological innovation, but also introduced a new principle in drug development: Chemical and physical properties must both be considered together in order to effectively address pathological issues. This research has been published in the Proceedings of the National Academy of Sciences (PNAS) and has garnered significant academic attention.”

“If you study and excel at it, apply yourself to securing a government position, but the research never stops.”

Having devoted over thirty years to academia, Professor Chiu has twice served on the National Science and Technology Council, taking on the responsibilities of a government official while consistently publishing academic findings. Professor Chiu emphasizes, “The research findings are not my achievement alone, but the result of the entire team’s efforts. The laboratory includes research assistants, graduate students, and postdoctoral researchers, who all play crucial roles in the research.”

He also generously shares that while on the team he does the key job of critique: “Even when experimental data or results don’t meet expectations, I make every effort to find the positive approach. This shift in perspective often leads to unexpected research breakthroughs. In addition, I frequently question the innovativeness and actual contributions of the research, such as: how our work differs from others, or how our findings address real-world issues—in order to stimulate in-depth team discussions.”

He believes that, whether engaged in research or government work, professional competence and an open mindset are foundational. Researchers must deepen their expertise and embrace innovation, while government officials should synthesize diverse opinions into policy programs. “During my time as a government official, I deeply experienced the importance of collaboration and integration.”

For young scholars, Professor Chiu’s advice is, “Though interdisciplinary thinking is becoming more and more important, you should still build a solid foundation in your specialized field first and master it, rather than pursuing interdisciplinarity for its own sake. Success in research depends not only on talent but also on long-term persistence. For example, among the students I’ve advised, the most successful are often not the smartest, but those who possess resilience and perseverance. Especially in the field of biomedical science, it's not enough to have achieved a breakthrough discovery; it must also withstand repeated verification.”