The field of cancer research is rife with unanswered questions, but – with the input and expertise of third-year internal medicine resident Juliann Shih – a team of scientists from Harvard Medical School, the Broad Institute of MIT and Harvard, and Dana-Farber Cancer Institute have answered one of those questions.
The question centers around aneuploidy – a state in which cells have an abnormal number of chromosomes. Does aneuploidy, the team’s research addresses, promote the growth of cancers, or is it a side effect of cancer cells’ fast growth?
Dr. Shih and her team published their findings in the June issue of Nature, which concludes that aneuploidy is not a side effect of cancer growth, but rather, stimulates cancer growth. Shih is the first author of the publication, “.”
Shih’s involvement in the project began eight years ago when she joined Boston’s Broad Institute as an associate computational biologist. She made her way to Boston by way of Southern California, her birthplace, and Taiwan, where her family moved when she was in the fourth grade. “I always wanted to come back to the U.S. for college,” she says. “I only applied to schools out East since I grew up on the West Coast, and I wanted to experience something new.”
Landing at the Massachusetts Institute of Technology (MIT), new experiences were abundant for Shih. “That was really difficult in terms of the academics,” she recounts, “but what I really appreciated was finding my love for medicine there (at MIT).”
As an undergraduate majoring in computer science and molecular biology, Shih found time to work in emergency medical services (EMS), where she discovered her passion for medicine and her “biggest community.”
Upon graduation, she “didn't quite feel ready to apply for medical school quite yet,” which is when she began working full-time with the Broad Institute. Drawing from her academic backgrounds in biology and computer science, Shih worked on numerous projects that contributed to a larger, multi-institutional project, .
Soon after the Human Genome Project was completed in 2003, the National Cancer Institute and the National Human Genome Research Institute jointly launched TCGA in 2005 with the goal, Shih explains, “(to) characterize the genomic features of essentially every type of tumor that they could get their hands on.”
Near the end of her time working full-time at the Broad Institute, Shih and her colleagues “started to notice that there was another subset of copy-number alterations that did not cover the entire chromosome arm, but actually just part of it (the chromosome).”
To analyze where these changes were most likely to begin or end in each chromosome, Shih developed an algorithm: Breakpoint Identification of Significant Cancer Undiscovered Targets, or BISCUT. “The bulk of the work” that Shih did in developing BISCUT happened during her time in medical school at Tufts University, where she took a research year between her third and fourth years to dedicate more focus to the ongoing project.
Once she graduated from medical school, the project was still ongoing, and matching with the Kirk Kerkorian School of Medicine’s Internal Medicine Residency Program brought about a cross-country move. Despite the distance, Las Vegas already felt a bit like home to Shih.
“I had essentially been coming out to Vegas every winter for a few years while living in Boston to rock climb, mostly at Red Rock,” she explains. “Coming here (for residency), the people I’ve met here, the environment, everything has been really excellent.”
Throughout the first two years of her residency, Shih had to contend with the time difference, finding time – often after long clinical rotations – to speak with her colleagues in Boston and New York. Shih and her co-researchers were able to complete the project, culminating with their ground-breaking publication in Nature, which, in Shih’s words, “essentially (proves) that these large aneuploidy events … are actually implicated in tumorigenesis and the generation of cancer as opposed to being passenger events that happen by chance.”
A notes that this research points “to new ways of guiding cancer treatment and developing targeted drugs.” When asked about the potential impact of her research, Dr. Shih says, “It’s difficult for me alone to speak to what that might mean for therapeutics going forward, but one can imagine, for example, exploiting that information and being able to target certain cells that have these sorts of alterations going forward.”
What does the future hold for Shih herself? Firstly, she will complete her internal medicine residency where she will serve as chief resident next year, possibly followed by a fellowship in pulmonary and critical care medicine. “I do eventually want to be a clinician,” she says, “but have my toes in the research world as well.”
