What is your background?
I'm from New York City and growing up there shaped my multi-cultural outlook on life in profound ways. I earned a bachelor's degree in biology from Caltech, and a doctorate in molecular and cellular biology from the University of Washington, based on dissertation research carried out at the Fred Hutchinson Cancer Research Center. In between, I worked for almost two years as a lab technician at the University of Pennsylvania. My postdoctoral training was at the National Institute of Environmental Health Sciences in North Carolina. So my education and training took me far and wide around the U.S. The different perspectives on life and science that I saw up close at the various institutions I trained and worked in has been very valuable.
Tell us about your research?
My research is focused on elucidating the molecular basis for mutations. Mutations are changes to the information coding content of DNA. Mutations often arise from damage to DNA that is inflicted by specific chemical or physical agents, called mutagens. Each mutagen tends to create a mutation signature, a molecular fingerprint or calling card. This is because a given mutagen tends to target specific sequence contexts in DNA and avoid others, while also creating characteristic patterns of base substitutions. We can infer which mutagens created a given set of mutations if we decipher what the constituent mutation signatures are.
What are some applications of your work?
One important application is to determine what causes mutations in cancers. Cancers can arise when some cell(s) accumulate mutations that give those cells a growth advantage. Cancers can have hundreds to hundreds of thousands of mutations. While relatively few mutations are thought to be responsible for a cancer's abnormal cellular proliferation, studying the entire set of mutations in a cancer can yield telltale signatures that implicate specific mutagens, including known or suspected carcinogens. Knowing what agents gave rise to the mutations in cancers can empower development of better prevention, diagnosis, and treatment strategies.
Another benefit of this research is that we're learning about the basis for the genetic variation that gave rise to the amazing diversity of life on Earth. We know from Darwin's theory of evolution that natural selection acts on the genetic variation within a population of biological entities. But what's not so well understood is the fundamental, molecular basis for the genetic variation in the first place. Our research also investigates the molecular basis for these background mutation processes that happen in living things all the time. We can potentially leverage this knowledge to devise more efficient ways to select for lab microbes with desireable traits, e.g., for biofuel or pharmaceutical production; for bioremediation of contaminated land; or for synthetic biology, with many possible downstream applications.
What got you interested in mutation signatures of carcinogens?
Cancer remains a major public health concern in Canada and throughout the world. Based on figures from 2015, the Canadian Cancer Society estimates that 2 in 5 Canadians will develop cancer at some point in life and 1 in 4 Canadians will die from cancer. I study mutation signatures in cancers because understanding these signatures can shed important new light on the role of specific carcinogens in the origin of cancers. In turn, this understanding can have important benefits for improving public health. In terms of cancer prevention, if we find that a suspected chemical carcinogen is indeed causing mutations in cancers, there would be greater impetus for governments to limit or eliminate exposures to that agent. With respect to diagnosis, if we can prove that a carcinogen's signature is found recurrently in certain type(s) of cancer, then early diagnosis could save lives among populations that are susceptible due to prior exposure or genetic makeup. Identifying the mutation processes that are ongoing within a cancer can also guide optimal choice of treatment. For example, bladder cancers often have a strong mutation signature due to the cellular enzyme APOBEC3A, and the bladder tumors which respond best to immunotherapy treatment have the most APOBEC3A signature mutations. This raises the possibility that other tumors which are heavily mutated by APOBEC3A could be promising candidates for similar immunotherapies. I think that we're going to make discoveries that will have clear, tangible benefits in the fight against cancer, so that's why I chose this field of research and am always looking forward to each day in the lab.
What’s the most interesting thing about you that we wouldn’t learn from your resume?
I do tweet (@KinChanPhD) from time to time about articles or news items that are interesting, informative, and thought provoking. I try to read broadly, to maintain a sense of the big picture beyond my own specializations, and mostly tweet about science, education, and sustainability issues
