A Mighty Molecule

DR. DAKE QI’S FOCUS on a minuscule molecule could lead to big breakthroughs in the treatment of heart disease, metabolic syndrome and psychiatric diseases.

The assistant professor in the College of Pharmacy, an MD/PhD who was recently recruited to the U of M following stints at Yale University and Memorial University of Newfoundland, is one of Canada’s foremost researchers of a protein molecule called macrophage migration inhibitory factor (MIF).

The molecule has been recognized as an inflammatory factor that plays a key role in regulating many diseases. Its effects are sometimes destructive, and sometimes protective.

“This is a very important molecule,” Qi says. “We’re trying to figure out its function, but we still have a long way to go.”

In a study published in The Journal of Clinical Investigation in 2014, Qi reported that in mice, an MIF homolog (a very similar, related protein) called D-dopachrome tautomerase (D-DT) protected the heart from injury during heart attacks.

Based on that finding, Qi is working on a treatment to improve patient outcomes after the standard therapy for heart attack, percutaneous coronary intervention (PCI). That’s the procedure in which a doctor inserts a stent to open a blocked artery.

Following a PCI, patients experience “reflow injury” that damages the heart. Qi aims to treat this damage by using D-DT, but there’s a hurdle: if the protein were injected into the bloodstream, it would quickly pass through the damaged area and not stop. Qi’s idea is to inject a combination of magnetic nanoparticles and D-DT.

Using a magnet, a doctor would then be able to stop the combined nanoparticles and D-DT in the affected area. The protein would slowly release into the damaged tissue. “If we can effectively do this, we will definitely improve patient survival,” the professor says.

Qi is also looking at the role of MIF in the development of metabolic syndrome, a cluster of conditions that occur together, are associated with obesity, and raise the risk of heart disease, stroke and Type 2 diabetes.

His lab collaborated with scientists at Shanghai Jiao Tong University on a study that found that MIF in the brain can regulate food intake behaviour. “This will be a potential mechanism to regulate how obesity happens,” he says.

Another research question is how MIF regulates psychiatric diseases. Qi is investigating whether the protein is associated with negative symptoms of schizophrenia.

The researcher says that after four years at Memorial University of Newfoundland as an assistant professor of biomedical sciences, he was drawn to join the U of M this past September by the superb cardiovascular research taking place here and the use of nanoparticles by College of Pharmacy researchers.

“I thought that if I moved here, I would have more of a chance to better my research career and expand my research potential,” he says.

Qi was raised in Harbin, China, and grew up wanting to be a doctor like his father, a cardiologist. After graduating in 1999 from medical school in Shanghai, he worked at a hospital for two years.

Deciding that he wanted a deeper understanding of disease, he came to Canada to earn a master’s in pharmacology and therapeutics at the University of British Columbia. He stayed on to complete his doctorate in pharmaceutical sciences. “When I finished my PhD, I thought, ‘I should do research. It will be a different way to help people.’”

Qi completed a postdoctoral fellowship at Yale University’s Cardiovascular Research Center from 2007 to 2010, then worked for four years as an associate research scientist at Yale.

“Research usually means you’re seeking the unknown,” he says. “So whenever I find a mechanism behind a disease – not a big step, a small step – it gets me excited. It’s like if you play chess, and suddenly you realize which way you can move to win.”