Muscle stem cells, tissue repair and ageing

25 May 2017

From the very first PC, Dr Tom H Cheung developed his love to science and technology and now, studying skeleton muscle stem cells to find cures for aged-associated diseases

Tom H Cheung (2015 Innovation Award) is an assistant professor at the Hong Kong University of Science and Technology in the division of life science, where he heads the Cheung Laboratory, which focuses on somatic stem cell biology. His laboratory is part of the Center for Stem Cell Research, the State Key Laboratory of Molecular Neuroscience, the Center for Systems Biology and Human Health and an affiliated member of the Division of Biomedical Engineering and Bioengineering Graduate Program at the university.

Despite his eminent career, Cheung claims he was not a good grade student at school and thinks the local education system puts too much emphasis on memorization and examinations. He believes he was fortunate that his parents immigrated to the USA, where he completed his higher education at the University of Colorado, Boulder .

“If I had stayed in Hong Kong, I would probably not be talking to you now as a university professor,” he says and he remembers it was a gift from his father that first stimulated an interest in science and technology.

“The greatest thing my dad ever did for me was to buy me a PC when I was twelve years old. It was running MS-DOS and it changed my life,” he says.

Cheung loved the TV-style games on the computer but later he found ways to crack and amend the game code so he could perform better and achieve higher scores.

“I admit it was cheating really but I found the process of cracking codes gratifying,” he says and remembers that shortly before he left Hong Kong with his family for the USA, something else triggered his scientific curiosity. By chance, he watched a morning educational programme about DNA and the human genome. Cheung was fascinated by the challenge of cracking the human genome just as he had cracked the computer game code on the PC given to him by his father.

At university Cheung elected to major in biochemistry. In his junior year, his mentor, Professor Xuedong Liu, hired him as an automation intern in his laboratory, using his computer skills to assist with inventories and database work. When that work was complete, Liu suggested he help out with a few experiments in the laboratory.

“I knew immediately this was the work I really enjoyed,” says Cheung.

University of Colorado, Boulder was well known for its ribonucleic acid (RNA) biology and it was Liu who suggested him doing a PhD. The human genome sequences were published at about this time and it was Cheung’s opportunity to indulge his interest in genetics.

“My project was essential to fulfill my childhood fantasy of cracking the human genome,” he says.

Not knowing where the regulatory sequences were that switched the genes on and off, he stacked up rat, mouse and human genomes and looked for similarity.

“I did coding on the computer and performed the conventional molecular biology and cloning experiments in the lab,” he says and he became more deeply involved in the field of comparative genomics. Studying the DNA sequence, genes, regulatory sequences, and other genomic structural landmarks of different organisms became his daily work.

“We spent a lot of time looking at the DNA sequences to try and understand it- it was a lot of fun,” says Cheung.

On completion of the PhD, Cheung decided to focus on stem cell biology and renowned biologists, Professor Leslie Leinwand and Professor Bradley Olwin at the university were very influential in his next move. They suggested he undertake post-doctoral studies at the Rando Laboratory at Stanford University, under Professor Thomas Rando, who is a world-renowned biologist in the area of muscle stem cell biology and stem cell aging.

Muscle is a good place to examine stem cell aging because its stem cells rarely divide and remain in a resting state and for a long time and were believed to be dormant or inactive. It was Cheung’s work at the Rando Laboratory which determined that they were not dormant but quiescent; in an actively regulated state and poised for action when a muscle is injured.

“The muscle stem cells can respond to a specific action in a very short time and my current research is about how they play a part in healing and body repair,” says Cheung explaining that human reparative capacity is generally very high but as humans get older they do not heal as well. Those older muscles still have stem cells but they do not act as fast as in young tissue.

Cheung says that this area of research could have a direct benefit for treating sarcopenia; the degenerative loss of skeletal muscle mass quality and strength associated with aging.

“If we could rejuvenate the stem cells, we could re-set their state. If we can find the reason for the muscle stem cell delayed response in old tissues, potentially that would be the remedy for the decline of muscle functionality in old age,” he says.

This is the field of epigenetics, the study of changes in organisms caused by modification of gene expression rather than alteration of the genetic code itself. These are the rules that tell a cell how to behave and Cheung explains that these epigenetic modifications can be changed. There are epigenetic differences in young and old muscle stem cells and it is possible to erase these epigenetic markers.

Cheung says a Croucher Innovation award in 2013 was critical to the success of his work because it allows his team “to take risks” and tackles these difficult questions.

Using skeletal muscle stem cell as a model system, his research team continues to decipher the molecular pathways that are essential for muscle stem cell function and the regulation of stem cell ageing. The long-term goal of his laboratory is to achieve better understanding of the molecular mechanisms of why tissue regeneration is impaired during ageing and devise therapies for aged-associated diseases using regenerative medicine.    

Dr. Tom H. Cheung received his B.A. (2001) and Ph.D. (2006) in Biochemistry from the University of Colorado at Boulder. He joined the Division of Life Science at the Hong Kong University of Science and Technology (HKUST) in 2013 where he current serves as an assistant professor. He is currently a member of the Center for Stem Cell Research, the State Key Laboratory of Molecular Neuroscience, the Center for Systems Biology and Human Health and an affiliated member of the Division of Biomedical Engineering and Bioengineering Graduate Program at HKUST. His research interest is in the molecular regulation of stem cell quiescence and activation and how these signaling pathways play a role in tissue regeneration as well as stem cell ageing using skleton muscle stem cell model.

To view Dr Cheung’s Croucher profile, please click here