Academic Spotlight: Xiaoyin Wang, MD

Xiaoyin Wang
Xiaoyin Wang, MD, MSc


Discovering Secrets of the Heart

Xiaoyin Wang, MD, MSc, brings an unusual breadth of experience to her position as a research specialist in the lab of Matthew Springer, PhD, professor of medicine in the UCSF Division of Cardiology. In addition to spending more than 30 years as a lab scientist studying cardiovascular pathophysiology – including working in Dr. Springer’s lab since 2007 – she cared for heart attack survivors for over a decade as a cardiologist in a Beijing hospital.

“I always use my knowledge in cardiology to design a research proposal and make it more relevant to the clinic,” said Dr. Wang. “Having that background helps my research, and allows me to troubleshoot problems and find better approaches.”

Born in Shanghai, Dr. Wang earned her medical degree from Shanghai First Medical College, now known as Fudan University Shanghai Medical College. She then completed her internal medicine residency and fellowship in clinical cardiology at the China-Japan Friendship Hospital in Beijing.

Her very first clinical rotation during residency was in the Critical Care Unit, where she cared for many patients with acute myocardial infarction (MI), or heart attack. “I learned how to diagnose MI and treat it with medication,” said Dr. Wang. “This experience with heart disease cases, such as MI, arrhythmia and heart failure, motivated me to continue in this field. If my first rotation had been another specialty, maybe I wouldn’t have chosen to become a cardiologist.”

Developing Research Skills

“Doctors shouldn’t just do their clinical work, but some clinical or basic research as well,” said Dr. Wang. “Understanding the mechanisms of heart disease is critical.” She was accepted at Peking Union Medical College, one of the top medical schools in the country, where she earned a master’s degree in cardiovascular physiology.

After completing her cardiology fellowship, she embarked on a busy clinical career at China-Japan Friendship Hospital, where she served as physician in chief for the cardiology department. Dr. Wang studied ways to diagnose patients with MI and cardiomyopathy using surface mapping. Similar to an electrocardiogram, which uses 12 electrodes to record and measure electrocardiac activity, surface mapping uses up to 120 electrodes placed all over the surface of the body to create a more detailed picture.

She spent more time learning about surface mapping as a visiting researcher at the National Cardiovascular Center in Osaka, then conducted in vitro electrophysiologic mapping at the cellular level as a visiting researcher at the Research Institute of Environmental Medicine at Nagoya University in Japan. Dr. Wang led clinical research to investigate the use of cardiac mapping to improve the diagnosis and treatment of MI patients, as well as lab research to study post-MI arrhythmias in animal models. In another lab investigation, she sought to learn more about a phenomenon called ischemic preconditioning, in which multiple short periods of reduced blood supply to the coronary artery may reduce cardiac damage from a subsequent heart attack.

In the early 2000s, Dr. Wang pursued her passion for research all the way to Virginia Commonwealth University in Richmond, Va., where she spent five years as a postdoctoral scholar in the lab of Rakesh Kukreja, PhD. She helped discover that pretreating animal models with the PDE-5 inhibitor Viagra (also known as sildenafil) could mitigate some of the harmful effects of a heart attack, and helped elucidate the novel mechanisms underlying this phenomenon.

Helping the Heart Recover from MI

Although she enjoyed working as a physician-scientist in China, Dr. Wang decided to stay in the U.S. after completing her postdoc to devote herself full-time to research. “There were so many opportunities to do research and learn more about the mechanisms of why MI induces so much inflammation,” she said. She interviewed for research positions on the West Coast and was recruited by Dr. Springer to join his lab in 2007.

One of Dr. Wang’s main areas of research within the Springer Lab is studying the therapeutic effects of bone marrow cells (BMCs) implanted into injured hearts following MI. This approach had previously shown promise, but Dr. Wang and her colleagues wanted to find out why it failed in clinical trials. In animal models, they found that BMCs harvested from older donors and those which had an MI were less therapeutic than BMCs from young, healthy donors. “That means something happened in the bone marrow after MI,” she said.

Taking their research a step further, Dr. Wang and the Springer Lab found that human post-MI BMCs from clinical trials were therapeutically impaired when implanted into post-MI immunodeficient hearts in animal models. They found that systemic MI-related inflammation may compromise the health of BMCs harvested from those donors. “One possible reason that the BMCs from human patients who had already had an MI did not appear to promote healing in the recipient animal model hearts was that post-MI BMCs were in the inflammatory state and problematic for therapy,” said Dr. Wang.

Fine-Tuning the Scarring Response

Another major area of Dr. Wang’s research is how to prevent development of heart failure following MI. After a heart attack, some heart cells die. The body senses the damage, and an intricate immune response kicks in. In the early stages, specialized cells called macrophages help clear away the wreckage of dead cells. Then another type of macrophage initiates a fibrotic process, forming scar tissue that can help support the structure of the heart. “Initial wound healing responses following MI are crucial in stabilizing the infarct scar to prevent rupture,” she said. “But excessive fibrosis reduces elasticity of the heart, which can contribute to subsequent heart failure.”

A fibrotic mediator called galectin-3 plays an important role in the development of fibrosis. The Springer Lab collaborates with Constance John, RPh, PhD, adjunct associate professor in the UCSF Department of Laboratory Medicine, who developed a galectin-3 inhibitor called Gal-3C to help fine-tune this post-MI scarring response. Together, the Springer and John Labs have been testing different doses of Gal-3C and protocols in animal models to try to find a “Goldilocks” response to MI: not too much scarring, not too little, just enough.

They found that Gal-3C had beneficial effects on various cardiac performance measurements, reduced scar size, and improved cardiac function in an animal model. Along with Dr. John, Dr. Springer and another collaborator, Dr. Wang is a co-inventor of a patent related to this therapeutic approach.

In addition to this molecular therapy, Dr. Wang and the Springer Lab recently began another collaboration with Anders Näär, PhD, professor of metabolic biology at UC Berkeley, to study gene therapy for MI. Together they are studying the use of a novel microRNA inhibitor in an animal model to discover whether it could have beneficial effects on recovery from MI.

Shaping Marijuana and Tobacco Policy

Some of Dr. Wang’s most publicized work has been in the Springer Lab’s investigations of the adverse effects of cigarette and marijuana smoke on cardiovascular function. That includes smoke directly inhaled by smokers, also known as mainstream smoke, as well as secondhand smoke. For example, she helped discover that just one minute of exposure to secondhand marijuana smoke substantially impaired blood vessel function for at least 90 minutes in an animal model. That study received widespread coverage, including on KCBS Radio, CBS News, and Fox News as well as in Forbes and U.S. News & World Report.

She also helped demonstrate that smoking and vaping of several types of tobacco products and marijuana impacted cardiac function and platelet activity and can contribute to cardiac arrhythmias. “Smokers are getting younger,” said Dr. Wang. “However, the impacts of smoking on the heart and blood vessels are usually ignored by the public.”

Her work has helped to inform public policy at a time when the legalization of marijuana in many states, as well as ongoing debates about the regulation of secondhand tobacco smoke, have been in evolution. Their marijuana results were cited in the 2015 report of the California Blue Ribbon Commission on Marijuana Policy, recommending that if marijuana were to become legal in California, it should be subject to existing clean air laws and bans on public indoor use. The Springer Lab has also shared their findings with policymakers in Alaska, Colorado and Oregon, as well as the lay press. “We want to inform the public, physicians and policymakers that smoke is smoke, and should be avoided whether the source is tobacco or marijuana,” she said.

“It’s already impressive when someone in a research group is the first author on one of the most impactful publications from that lab, but Xiaoyin’s many papers from this lab actually include two of our group's best-known reports,” said Dr. Springer. “One was the 2011 demonstration in Science Translational Medicine in an animal model that experimental cell therapy for heart attacks using a patient’s own bone marrow cells is hindered by the effects of age and the disease state on those cells. The other is probably our best-known work: her 2016 paper in the Journal of the American Heart Association showing in an animal model that secondhand smoke from marijuana has the same adverse effects on vascular health as secondhand smoke from tobacco. She is continuing to make key discoveries related to the treatment of cardiac diseases and understanding how inhalation of smoke leads to vascular problems.”

Besides her enthusiasm for research, Dr. Wang enjoys traveling internationally, spending time with friends closer to home, and savoring the beauty of the Bay Area.

“I really enjoy working in the Springer Lab, doing research and data analysis, and writing papers,” said Dr. Wang. “I also like teaching postdocs and students how to do MI surgery in animals, echocardiography, hemodynamics, and other procedures in the lab…. This field of research is complicated. It requires knowledge of cardiology, clinical care, research skills, biology, physiology and pathophysiology. It’s very helpful to have more than one area of experience. When I worked as a cardiologist, I saw so many MI patients. That inspired my interest in doing clinical and basic research to see how MI induces inflammation, fibrosis and subsequent heart failure. Now through research, I get to investigate different possible treatments for MI.”

- Elizabeth Chur