The clue in the plasma
As a medical student, Dr Rossa Chiu realised she was learning about things already known, but also that there was so much more out there to know. As a researcher, she investigates disease just as her childhood heroes Sherlock Holmes and Hercule Poirot did crime, navigating the first tell-tale clues to stop medical mysteries in their tracks.
“I always loved puzzles, and that’s why novel methods of disease diagnosis drives me,” Chiu says, “I work with all kinds of doctors and researchers on real problems. Diagnosis is just the tip of the iceberg, so the timing, depth and other factors of finding the first key is an essential first step.”
Traditional diagnostics analyse diseased tissue, but plasma-based diagnostics allow a safer blood-based test that also improves early detection of cancer. Pathologists usually study intact cancer cells, but dead cells also release their DNA into plasma, the fluid part of blood. “Rooting through plasma, which is basically the rubbish dump of dying tissue, was the best decision ever,” Chiu jokes. The fascination started during her doctoral studies, as her mentor was the first person to identify fetal DNA in maternal plasma. Chiu then worked to apply this discovery as a diagnostic test, eventually succeeding in using it as one of the first non-invasive prenatal tests for Down’s Syndrome. The test is a high-performance screen now used in over 100 countries globally, and has proven to significantly reduce use of other alternatives such as amniocentesis, which carries significant risks. On a basic level, the test detects molecular signals in plasma, scrutinising DNA features that change in pathological situations. To the patient, it’s a simple blood test, but researchers analyse 10 million DNA molecules per sample, going through the cell dump of DNA to find answers.
Always looking forward, Chiu is working on enhancing plasma-based prenatal testing for more challenging applications such as mapping out the entire genome, twin samples, and other prenatal diseases. “My own personal holy grail is now tackling cancer, because current tests are so limited, and usually after symptoms are present. The ultimate goal is to develop a test for pre-symptomatic cancer to lower the disease burden and save lives,” Chiu explains.
Chiu’s latest breakthrough is in plasma DNA tissue mapping, building on research on liver cancer and pregnancy signals. The mapping project analyses data in plasma to pinpoint which organ is releasing DNA into the sample and at what proportion. “It sounds simple, but it’s like a CT scan of the body, identifying abnormal DNA, where it’s coming from, and fixing multiple organ issues,” Chiu says, “It’s a great step towards early detection and prevention, and gives a much more efficient full-body view.”
Cancer is a common worry, but people going in to the doctor’s office looking for cancer are often disappointed because of the lack of accurate testing before symptoms appear. The currently available tests rely on protein markers, not the most conducive for early detection, and most others use these markers to test and monitor treatment progress after a patient becomes symptomatic. Plasma-based testing is convenient, non-invasive, and can detect many types of cancers at once, and hopefully earlier. “We have already had some success because the abnormal DNA in cancer cells can be more easily measured through plasma. Unlike traditional testing which tries to identify markers, we look for all abnormalities, which doesn’t restrict us to any particular kind of cancer.” Chiu says. This wider initial focus allowed a greater analysis pool, including cases where symptoms were already present which had clear biomarkers in blood. Once these were identified, it opened the door to more sensitive tests for early detection, such as DNA methylation analysis for plasma-based tissue mapping to identify the origin sites of the cancer.
As an upcoming Croucher fellow, Chiu plans to further her plasma-based diagnostic research to maximise pathological information extraction from each sample. “There’s so much more information available, if only we know what to look for. I want to show that one blood sample can address a wide variety of diagnostic and treatment needs, from organ transplants to autoimmune diseases and other issues,” Chiu says. By pushing tests’ sensitivity to squeeze more clinical information from chromosomal abnormalities, tissue mapping, and other signals, she hopes to lay the foundation for cost-effective and accessible tests for early cancer detection. Chiu is keen to emphasise the importance of focusing on better diagnostics. “Every cancer has markers or distinctive characteristics, and fine-tuning the way we look for them can lead to very real change in terms of public health, and the way we approach preventive care and treatment,” she explains. Several major cancers are usually detected in later stages, but proactive screening and earlier detection could mean better understanding of cancer behaviours and lifesaving progress in cancer treatment.
Personalised medicine is also a major trend, one which Chiu strongly feels will continue. “We understand now that there’s no one-size fits all approach. It’s like coffee—we react to everything differently, and our illnesses react and behave differently,” she says. With an increasing interest in precision medicine, doctors need to know what markers to look for, what tests to use, and have the tools to do so.
Teaching came as a serendipitous twist in Chiu’s story. Drawn to the biochemical aspect of pathology, she was serving her residency at the Prince of Wales Hospital at The Chinese University of Hong Kong. When an assistant professorship opened up, she applied, thinking it would round out her research experience. “I didn’t think so much about the teaching part,” she laughs, but it came naturally enough that she was voted Teacher of the Year by the students at the end of her first year. “You have to be a good teacher to be a good researcher,” Chiu explains, “Otherwise research and progress would become unsustainable and static without new ideas and perspectives.”
Encouraging questioning minds is especially important now, when the research field is increasingly interdisciplinary and researchers super-specialised. Given the limited funding available and common research questions, pooling ideas and expertise from super-specialists is key to moving forward comprehensively across several fields. “My own field has changed so much, and I couldn’t have predicted I would be doing what I do,” Chiu says, “So be curious! It doesn’t matter what field, just find your own detective story, and your passion will drive you and science forward in unexpected ways.”
Dr Rossa Chiu received her medical degree at the University of Queensland in Australia, and her PhD at The Chinese University of Hong Kong. She is a Fellow of the Royal College of Pathologists of Australasia, the Hong Kong College of Pathologists, and the Hong Kong Academy of Medicine (Pathology). Dr Chiu has published over 140 peer-reviewed research articles and has 20 granted patents, as well as a number of awards for her research. She is currently the Choh-Ming Li Professor of Chemical Pathology and Assistant Dean of Research in the Faculty of Medicine at The Chinese University of Hong Kong, and was recently awarded a Croucher Senior Research Fellowship.