Fishing for a cure
From his lab in Hong Kong, Professor Zilong Wen (Croucher Senior Research Fellowship 2019) is at the forefront of global blood cell research, and the tiny zebrafish is key to his work.
When he isn’t teaching, the Division of Life Science faculty member at the Hong Kong University of Science and Technology (HKUST) is researching hematopoiesis, also known as blood cell formation.
These cells are derived from self-renewing hematopoietic stem cells. But as we get older or ill, the capability of the stem cells to supply our blood system will be reduced. The dysregulation can lead to disease – something Wen is trying to combat.
Wen’s lab has the largest zebrafish facility in Hong Kong. Testing on this tropical fish, often found in home aquariums, has several advantages. “I have hundreds of thousands of fish in my lab and they are from hundreds of different genetic strains of many generations of fish. If I were to replicate this research using mice instead of fish, I wouldn’t be able to fit all the mice in my lab,” he said.
Moreover, mice and other mammals have a longer gestation period. The study of hematopoiesis requires examining cell proliferation and differentiation over multiple generations, so using an animal with a short life cycle is ideal. In fact, a zebrafish egg grows as much in a day as a human embryo grows in a month.
Of course, as every child learns in primary school, humans certainly are not fish. However, our blood system is remarkably similar to that of a zebrafish. And thanks to the near-transparent bodies of the fish embryos, scientists can measure the development of internal structures.
“We can observe blood vessels and circulating blood cells in a zebrafish embryo quite easily because the fish are see-through,” Wen said. “Unlike mice, we don’t need to dissect their bodies.”
Wen uses non-invasive techniques such as time-lapse imaging to monitor circulatory activity throughout the fish. Along with the flow of other blood cells, he is also able to track the progeny of the hematopoietic stem cells in a process called photo-inducible lineage tracing.
In May, Wen’s lab discovered a new type of cell found within the zebrafish epidermis. Called metaphocytes, these cells play an important role in the fish’s immune system. It would thus be fascinating to find out whether metaphocytes also exist in humans and, if they do, what biological function they play.
In the past, the zebrafish has provided a powerful model to tackle challenges in developmental biology. Now they are being used to study many kinds of human diseases, including cancers. Who knows what else the zebrafish could show us?
Professor Zilong Wen is a faculty member in the Division of Life Science, Hong Kong University of Science and Technology (HKUST). He obtained his Bachelor of Medicine from the First Military Medical University (Southern Medical University) in China and PhD from Rockefeller University, USA. After postdoctoral training with Irving Weissman at Stanford University, he established his own laboratory as a principal investigator at the Institute of Molecular Agrobiology/Institute of Molecular and Cell Biology, Singapore, in 1999. In 2008 he joined HKUST. Wen has made substantial contributions to the understanding of the development of blood cell lineages. Using genetics, state-of-the-art imaging techniques and interdisciplinary methods, his team systematically uncovered the origin, developmental regulation, and tissue-specific function of hematopoietic stem cells, T lymphocytes, and microglia. Professor Wen received a Croucher Senior Research Fellowship in 2019.
To view Professor Wen's Croucher profile, please click here.