A bacterium can live in one person’s stomach for decades without causing serious harm. In another, the same type of bacteria can eventually contribute to gastric cancer. Lexington resident Chao Zhang wants to understand why.
Zhang, an assistant professor at Boston University’s Chobanian & Avedisian School of Medicine, recently received a five-year, $2.2 million grant from the National Institutes of Health to study how interactions between the human body and its microbiome, or the ecosystem of microbes that live in human intestines, change over time.
For Zhang, a career in biomedical research was not always the plan. Zhang was initially trained in automation at Beijing Institute of Technology. “I wanted to be a software engineer at that time, so I found work at several companies, including Samsung, for almost five years,” Zhang said.
Zhang found himself wanting a greater challenge, and began his doctoral studies in computer science at the University of Missouri. He was also interested in medicine — his parents had worked in a hospital, so medicine was a familiar part of his upbringing. Zhang began research in bioinformatics under Professor Dong Xu.
“[Bioinformatics] is very interesting because it’s a combination of computer science, medicine, and life sciences. You use computational skills either to help discover fundamental biological questions or to help clinicians or physician-scientists solve clinically oriented problems,” Zhang said.
As a postgraduate researcher at Weill Cornell Medicine, Zhang researched gastric cancer outcomes, which were linked to bacteria in the gut microbiome.
“There is one well-known bacterium called Helicobacter pylori… Some people infected by this bacterium never develop cancer, even if they have the infection for 40 years or longer,” Zhang said. “But some patients, after ten or 20 years of infection, develop gastric cancer. We wondered why some people are affected in this way and some people are not.”
Outcomes could be driven by variations in the bacteria themselves, but they could also reflect differences among hosts. That led him to focus on the interaction between the two: how microbes affect the human host and how the host affects the microbes in return. Advances in data collection and artificial intelligence have made it increasingly possible to examine those relationships.
“We have around 30,000 genes, and there are so many different microbes,” Zhang said. “You need to find the associations or correlations between them — either how those microbes affect the human body and gene-function changes, or how the human immune system affects the microbiome. It’s very high-dimensional data.”
That complexity, Zhang said, makes the field well-suited for newer computational approaches.
“This is the right time to introduce those advanced computational technologies into this field,” he said. “We have the data, and we have algorithms and technologies that have been proven in other fields.”
The NIH grant will be administered over five years. Currently, Zhang is working on two major projects. One involves studying how the microbiome affects or indicates the development of gastric cancer. Another studies how immunotherapy affects the microbiome ecosystem, and whether the microbiome can be used as an indicator of treatment outcomes.
In the long term, Zhang and his team hope to better understand how host-microbiome interactions evolve over time. To achieve this goal, they will need to collect more data over time to validate their cutting-edge models.
“The microbiome and human host interaction isn’t just something that happens at one moment… So far there isn’t a good computational method to evaluate these time-series changes,” Zhang said. “We are working on a new methodology to better model this interaction over time.”
Zhang also sees a different challenge confronting academic science: persuading talented young people to enter the field at all.
“It’s difficult to find future scientists,” Zhang said. “Compared with five or ten years ago, nowadays most students graduating from college want to work [in the private sector]… It’s really challenging to find talented students who want to devote their efforts to scientific research.”
Zhang moved to Lexington with his family in 2022 when he joined Boston University. He spends much of his time on research, but in his free time, he enjoys hiking with his two children, both of whom attend Lexington Public Schools.
“We love Lexington,” Zhang said. “It’s a nice, quiet town with history. That’s why we chose it, and it also has really good schools.”
As artificial intelligence becomes increasingly prominent in medicine, Zhang said he is especially eager about its potential to improve patient care.
“I’m quite excited to see the progress in applying AI in biomedical research or the biomedical field,” he said. “Especially for diagnosis, radiology, and pathology, there are so many successful applications to eventually benefit patient treatment.”