A framework for Hong Kong entrepreneurs
Chan’s interest in biological research stemmed from the time when she was an undergraduate at the University of Hong Kong, where she was involved in encoding the virus causing the Severe Acute Respiratory Syndrome (SARS) and rapid diagnosis of SARS, at the peak of the outbreak. “This experience has influenced my career deeply. I found that advances in treatment for diseases can have a really big impact on our health, for society. I decided to enrol in a graduate program which allowed me to study an important area of human disease”, Chan said.
Chan conducted cancer research in graduate school at the Department of Oncology of the University of Oxford. While at Oxford, she worked with Sir Walter Bodmer to investigate the role of a transcription factor, CDX1, in the development of colon cancer. CDX1 is a transcription factor important for normal development and differentiation of intestinal epithelial cell. In tissue samples of patients with colorectal cancer, researchers found that the CDX1 gene, and a related KRT20 gene, were down-regulated. Chan’s hypothesis was that dysfunction of the CDX1 gene and KRT20 expression was related to the development of colorectal cancer. To better understand the roles and interactions of CDX1 and KRT20 genes, Chan conducted a series of experiments to study the interactions between the CDX1 and KRT20 genes. This study confirmed the role of CDX1 as one of the key factors of intestinal differentiation, and paved way for cancer stem cells research with CDX1.
In her graduate research, Chan has used traditional methods, such as cell lines, to understand the biological basis of colorectal cancer, but increasingly, she recognised the limitations of these methods and felt the need to learn new techniques to advance her research.
After completing her PhD at Oxford, Chan won a Croucher Fellowship and moved to Professor Calvin Kuo’s laboratory at Stanford University to study cancer modeling and driver oncogene validation in a highly tractable primary organoid system. The system combines the accurate multilineage differentiation and physiology of an in vivo system with the facile in vitro manipulation of transformed cell lines. With this method, Chan and other colleagues were able to culture organoids with both epithelial and mesenchymal components from small intestine, colon, and stomach using an air-liquid interface methodology. Using the air-liquid interface system, she was able to assess the requirements for combinatorial oncogenic transformation systematically in colon organoids, obtaining in vitro reprogramming of primary intestinal epithelium to adenocarcinoma and recapitulating multi-step colon tumorigenesis.
Chan is thankful to have received support from the Croucher Foundation to carry out this research at Stanford, which offered her opportunity to work with top scientists on cutting-edge research. At the same time, she was exposed to the entrepreneurial spirit prevalent in the Silicon Valley. During this time, Chan attended a summer institute for entrepreneurs program, and was able to take this opportunity to learn skills and theory in business management and entrepreneurship, such as how to commercialise technology through licensing.
After Stanford, Chan moved back to Hong Kong to start research with Professor Dennis Lo at the Chinese University of Hong Kong. At the Chinese University of Hong Kong, Carol continued her passion in technology and cancer research and has participated in a project to detect genome-wide hypomethylation in plasma using a new massively parallel sequencing technology.
Genome-wide hypomethylation is a well-known phenomenon in most types of cancer. However, Chan explains that detection of such changes in plasma is like finding a needle in a haystack. With the advances of massively parallel sequencing, the group was able to observe tumor-associated copy number aberrations as well as hypomethylation in liver, breast, and lung cancer, as well as in smooth muscle sarcoma, and neuroendocrine tumours. Thus opening the possibility for a cost-effective and non-invasive approach to cancer detection.
Combining her interests in cancer biology and technology and entrepreneurship, Chan recently joined the Innovation and Technology Commission for the Hong Kong SAR Government. In her new role she promotes and supports applied research and development, and technology transfer and application, and is working towards a robust and flexible framework for a new generation of entrepreneurs in Hong Kong.
Chan received her bachelor’s degree in biology from the University of Hong Kong. Chan then moved to Oxford University to study her PhD in molecular oncology at Oxford University, where she graduated in 2009. She then moved to Stanford University as a Croucher postdoctoral fellow. She was also an alumnus of the Summer Institute for Entrepreneurship at Stanford Graduate School of Business. Chan has published articles in international scientific journal including Lancet, Nature Medicine, and PNAS.
To view Carol Chan’s personal Croucher page, please click here.