How TMU’s pharmacogenomics program became Taiwan’s research leader:

An interview with Prof. Wei-Chiao Chang

With a bachelor’s degree in pharmacy, a master’s degree in pharmacology, and a secure and challenging job reviewing clinical trials for Taiwan’s Food and Drug Administration, friends were amazed that Wei-Chiao Chang would choose a wandering life doing Ph.D. research abroad.

But at that TFDA desk fifteen years ago, he was struck by clinical trial results that showed some drugs performed better for Caucasian patients than for Asian patients. He was deeply curious about why the two populations responded so differently.

This question led him to propose doctoral research in this area. With financial support from Taiwan’s government and a UK Overseas Research Student Award, he gave up his good job to move to Oxford, the English-speaking world’s oldest university.

Prof. Anant Parekh was the young scholar’s supervisor, and Prof. Chang describes him as a remarkable educator who inspired him to become a scientist. So when he graduated in 2007, his curiosity again led to a career move across the planet – this time inspired by Japan Biobank research.

Prof. Yusuke Nakamura’s pioneering genomics studies used the clinical samples from the biobank he led as well as genome-wide association studies (GWAS) to examine genome-wide variants in individuals that were associated with traits. The Japan Millennium Project helped fund Prof. Nakamura’s lab as it achieved global eminence in the new specialty. After the young Taiwanese scientist inquired by email and later was interviewed, he was invited to join the famous RIKEN institute that leads Japan’s biomedical research.

Dr. Chang’s research at RIKEN examined genetic variants affecting asthma and atopic dermatitis. While he said that a child’s chance of developing these diseases is multifactorial, involving both genetics and environmental interactions, Dr. Chang sequenced 2500 clinical samples and came up with a winning hypothesis. One of the body’s calcium channels called Orai1 that affects the immune system and inflammatory reactions indeed varied widely between populations, with helpful implications for clinical decisions.

From overwork to work-life balance

After two years of fruitful research at RIKEN, Dr. Chang was at a crossroads. In Japan, the salary was better than in Taiwan, and RIKEN was the world’s leading genomics research institute, but the working hours were very long. So when Prof.

Hank Juo and the president of Kaohsiung Medical University recruited Dr. Chang, he set up his own lab.

No job is easy in the beginning, he recalled with a laugh, but the salary was much lower and he was still working just as hard as in Japan! Plus he commuted to Taipei each weekend for three years to see his wife, even when their son was born.

Fifty papers came out of those four years, making Prof. Chang one of the Kaohsiung school’s leading scientists in terms of productivity. But when TMU’s President Yun Yen recruited him in 2012 to set up a master’s degree program for Clinical Pharmacogenomics and Pharmacoproteomics, he jumped at the chance to join his family, and started a new lab in the Pharmacy Department.

This lab that Prof. Chang started with just three technicians, two undergraduates and one Ph.D. student has more than tripled in workforce. Nearly 20 people work in the lab now, and sixty percent of his grant money goes straight to student workers. “I hope to improve the economic condition of every student, so that they can fully focus on their research without worrying about the cost of living in Taipei,” he said.

While in the past his students found the lab’s working hours extremely long, now Prof. Chang encourages work-life balance. His lab meetings are on Tuesday evenings so clinicians can attend. And he always serves a nice meal then “because students never have much money.”

“I never say no when someone requests time off,” he said. “Life is not science – it can’t be measured by a very few variables. Life is an art. It should be played and enjoyed with love.”

Pharmacogenomics: how drugs and genes affect health

So Prof. Chang became the father of pharmacogenomics at TMU, and established Taiwan’s leading lab in this fast-growing area of study. He explained: “ ‘Pharmaco’ represents pharmacology, which is the study of how drugs affect the body, while genomics is the study of genetic variants between individuals and populations.” Thus there is no perfect medicine, he said, precisely because people respond differently to the same drug.

Because efficacy varies, people require different dosages. And some drugs that help most people can cause dangerous adverse drug reactions in others. His lab cooperates with many physicians to collect clinical samples. Then DNA is extracted from blood, and these samples are sequenced and analyzed using a bioinformatics approach to address clinical questions.

For example, while intravenous immunoglobulin (IVIG) is the main treatment for Kawasaki disease, some patients have persistent fever after this treatment. These patients are defined as IVIG resistant.

With help from Dr. Ho-Chang Kuo’s Kawasaki disease center at Kaohsiung Chang Gung Memorial Hospital, Prof. Chang and one of his doctoral students performed a genome-wide study and calculated weighted genetic risk scores.

This led them to establish a predictive model integrating the additive effects of all 11 single-nucleotide polymorphisms to better predict responses to IVIG. Their study was accepted for publication in Circulation Genetics earlier this year.

New frontiers: T cells and dynamic monitoring

Now Prof. Chang’s lab is focusing on sequencing T-cell receptors to define human immunity, and he’s working with TMU colleague Dr. Shiuh-Bin Fang to identify genes resistant to salmonella using Taiwan DNA samples.

Asked what new milestones lie ahead for his lab, Prof. Chang said, “Single-cell sequencing for immune repertoire.” He explained that T cells respond to many things, but this diverse response is the safest and healthiest condition – for when immunity is narrowly targeted, it is like sending an army in one direction while leaving other sides unguarded.

Prof. Chang said he and Prof. Mai-Szu Wu, superintendent of Shuang Ho Hospital, just published a paper addressing potential correlation between the immune repertoire and erythropoietin response in end-stage renal disease patients.

“We started to establish immune sequencing four years ago [in 2013]; probably we were the first team in Taiwan to do this,” he said. “Now we know how difficult this is. But it is very useful – especially dynamic monitoring for cancer treatments, especially for immune therapy.”

Marching to a different drummer

Prof. Chang won TMU’s award for best teacher this year; his lectures are very popular as well. His lab crew includes Thai, Malaysian, Indian and Malawian students, so clearly language barriers do not slow down the bench work.

TMU’s pharmacy YouTube channel Pharmixperience has posted an interview he gave to students. He said, “They wanted to know why I didn’t just stay with the TFDA or work as a pharmacist in the hospital, because it’s a good and secure job,” like the jobs the students have been told to aspire to.

The answer is temperament. Prof. Chang’s mentor had advised him that his personality needed the challenges of research, not the security of dispensing medications or working for government.

He said another plus of the scientist’s life is what many academics dread: publishing. “I like writing,” he said. Besides many scholarly papers, he has written two books and maintains a blog on Facebook.

Prof. Chang loved his time in England enough to share his photos in a book to convince Chinese-speaking students to study at Oxford. (His perfectionism meant waiting for only the rare sunny days, or waiting for hours for a vista to be free of cars so he could take the best possible photos.)

This book doesn’t just help students: he donated its proceeds to Taiwan’s Make A Wish Foundation. This charity gives children with cancer unusual opportunities and experiences, like travel and meeting their heroes.

“These children have so little time, and we have so much,” he said. “We have to process a lot of material into just one drop of useful product in the lab. For these children, we are the catalytic agents: We should turn their many tears into smiles – at least once.”

For interviews or a copy of the paper, contact Office of Global Engagement via global.initiatives@tmu.edu.tw.