Whenever my mother took me to morning wet markets in Malaysia, I would go straight to the fish vendor and sit there looking at all sorts of different fish. I always wanted a fish but my mother would stop me, as I didn’t have a particularly good track record of keeping pets. Now, I am surrounded by thousands of fish as I use the zebrafish model to study how blood and lymphatic vessels develop. Zebrafish, a popular pet fish, is an excellent animal model for biomedical research as it has a highly conserved genetic control of development and disease. Importantly, by fluorescently tagging specific organs of the fish, we can follow how these organs develop in real-time because zebrafish embryos are transparent during development and develop rapidly. As human cancer cells can be transplanted to both zebrafish embryos and adults, we can also model specific cancer cell behaviours, observe the molecular drivers of metastasis, and test the efficacy of new cancer drugs. As a vascular biologist, I use zebrafish with fluorescent blood and/or lymphatic vessels and observe how they grow, and respond in diseased conditions. I can spend hours looking at these colourful vessels under a microscope without getting bored because they are so beautiful! It is important to study how blood and lymphatic vessels develop as they play roles in various human pathologies such as cancer, chronic inflammation, and organ transplant rejection.
My main research focus is to generate and characterise genetically modified zebrafish (zebrafish transgenics) that enable visualisation of the dynamic activity of key signalling pathways for blood/lymphatic development in real time. Apart from development, we are interested in utilising these zebrafish transgenic lines to understand molecular mechanisms of blood/lymphatic vessels in various pathological settings in real time. Apart from this, I am interested in uncovering new lymphatic genes that may have functions in both developmental and pathological lymphangiogenesis. We are hoping to utilise the information we gain from this research to identify novel therapeutic targets/agents for cancer. One discovery that I am particularly proud of is when I contributed in the generation of the first lymphatic “atlas” that described all the lymphatic vessels in zebrafish larvae. This was made possible due to us generating the most lymphatic-specific fluorescent transgenic line in zebrafish at the time. This allowed us to visualise previously hard-to-see lymphatic vessels in the face and the intestine of the zebrafish and I even had the privilege to name some of these vessels. Using this information, we demonstrated that lymphatic vessels in fish respond to inflammatory stimuli from immune cells and also revealed that a subset of lymphatic vessels originate from a non-venous origin, something that has never been live-imaged before. Many researchers in the field have also used the tools and information we generated to 1) identify various new genes essential for lymphatic development, 2) show that lymphatic vessels in the heart contributes to cardiac regeneration in fish, and 3) identify a novel mural endothelial cell population that may contribute to clearance of brain waste and brain vascular regeneration.
The angiogenesis and lymphangiogenesis field are rapidly growing and so, it is essential for me to be in an environment that enables me to continue doing cutting-edge science. I am therefore excited to be part of the Peter MacCallum Cancer Centre which is situated right in the heart of the biomedical Parkville precinct, with excellent world-class facilities. Here at PeterMac, I am working side by side with scientists making actual impact to lives of cancer patients. Also, I see cancer patients every day when I come to work reminding me of how important it is to progress our understanding of human disease via research. I see research as a huge team effort. I believe that whatever small discoveries we make regardless of it being basic or translational, will one day collectively contribute to treatments for human patients. This motivates me to strive through the harsh environment of academia. I hope one day, the tools and information I generated would contribute to the betterment of human health and zebrafish would be world famous!
Dr Kazuhide Shaun Okuda is a Postdoctoral Fellow in the Hogan laboratory, which is part of the Organogenesis and Cancer Program within the Peter Mac Research Faculty. His expertise includes vascular biology, zebrafish research, disease modelling, imaging, and drug discovery. He can be contacted by email at [email protected]
Google scholar: https://scholar.google.com/citations?user=HvKo1eMAAAAJ&hl=en