Meet Nicholas Chia, PhD, University of Illinois postdoc fellow turned associate director of Mayo Clinic's Center for Individualized Medicine's Microbiome Program and Department of Surgery consultant. If you’d told Chia during his postdoc days that he would wind up at Mayo Clinic, he would have laughed you out of the lab. He is by no means a surgeon—to date, he’s never set foot
in an operating room.
You see, Dr. Chia is actually a physicist.
Scientist to clinical consultant
While Chia’s education is in physics—he earned his bachelor’s from Georgetown and his PhD in Physics from The Ohio State University—he claims to have never really studied physics or worked on a physics problem, per se, since his days as an undergrad at Georgetown. His graduate work dealt with statistics and sequence alignment, teaching him how to manage rare events, big data, and computational challenges, which built a foundation for things to come.
After graduate school, Chia landed at the University of Illinois at Urbana-Champaign as a postdoc under renowned biophysicists Carl Woese and Nigel Goldenfeld, modeling microbial dynamics in evolution and studying the origins of life. While working at the Institute for Genomic Biology at Illinois, Bryan White asked him to help analyze a new pyrosequencing data set from the microbial communities in the bovine rumen. The technical knowledge Chia picked up in graduate school aided him as his research interests turned toward microbial evolution and microbiomes. Then, thanks to the Mayo Clinic and Illinois Alliance, Chia was introduced to the idea of microbiome research in a clinical setting.
Fast forward to Rochester, Minnesota. Now on board at Mayo Clinic, Chia went from working with a theoretical physics group studying the origins of life to working in a major medical center, attempting to apply theoretical physics knowledge to medicine. Besides his leadership of the Microbiome Program and consulting for the Department of Surgery, he also has an academic appointment as assistant professor of biophysics. Chia has become an expert on the human microbiome—particularly in modeling microbial community and metabolic dynamics—and was recently awarded an R01 from the National Institutes of Health (NIH) to study the effects of the gut microbiome on colorectal cancer.
Dr. Chia’s transition from academic research to clinical research has not been without challenges, however. Being completely new to a medical center research environment, Chia has had a learning curve to overcome. Understanding clinical flow and how to interrupt the flow to get patient consent and collect samples was brand new, but key to knowing what is and isn’t practical for research projects. Chia feels in some ways that it may have been easier for him to pick up on how to get things done at Mayo because he’s learned everything from scratch. Interestingly, he’s also found that physicists and surgeons have a lot in common—they both tend to be very direct and expect results quickly—so he feels right at home. Chia says he’s managed the transition well by keeping an open mind. As a result, his work at Mayo Clinic is flourishing.
Innovative methods for researching the microbiome
Chia’s experience at Illinois enabled him to take a different approach to studying the microbiome and colorectal cancer (CRC). His lab at Mayo Clinic uses a systems biology and modeling-heavy approach that allows them to model the metabolisms of all
the individual microbes in the gut and then build a predictive model of what happens over a period of time. His lab uses this model to predict which metabolites and toxins will be generated, how stable the microbiome is, and what the population
fluctuations look like. The biggest difference in their approach, compared to a typical approach, is looking at a dynamic model versus a snapshot of a specific point in time. The dynamic model allows a better capture of overall exposure to toxic compounds. In the case of CRC, Chia’s lab is mainly focusing on the role of proton balance in the gut and the effects of hydrogen sulfide exposure on colon cell.
Hydrogen sulfide is known to be one of the toxic metabolic byproducts generated within the colon that may contribute to carcinogenic DNA damage. It’s also known that some microbes, like sulfate reducing bacteria (SRB), contribute to hydrogen sulfide production. However, there are also microbes in the colon, such as methanogenic archaea, that help remediate hydrogen sulfide accumulation by competing with SRBs for protons (H+), and could play a protective role in keeping the colon healthy. By modeling the changes in the microbiome over time, Chia’s lab will be able to determine if a person is at a greater risk of developing CRC due to large spikes of toxic metabolites or if chronic exposure is the more likely culprit.
Translating scientific discovery to preventive medicine
The research project, funded by Chia’s R01 from the NIH, is titled “Microbial Metabolic Toxicity Drives Colon Cancer.” In addition to gastrointestinal cancer clinical researchers at Mayo Clinic, the research team includes Nigel Goldenfeld and Bryan White—Chia’s former postdoc advisors—as Illinois collaborators. Through this Alliance facilitated project, Chia aims to better understand
the environmental components of CRC and settle certain questions about the role of diet, the environment, and other compounds involved in carcinogenesis. But the goal isn’t necessarily to cure colorectal cancer.
“Instead of moving to detection and treatment, I really want to get us toward prevention—which is the next step—to not have this problem to begin with. And it’s a very western problem. What is it about our diet that is causing this? Is it something we can prevent? Obviously, if we figure this out it would mean there may be behavioral changes needed to change our chances
of colorectal cancer, much like how we put on sunscreen [to prevent skin cancer],” Chia says.
He believes this research should be able to tell us what some of the causes of CRC are and how to prevent or ameliorate them by getting rid of certain microbes or adding in beneficial microbes that could compete with the so-called “bad” microbes. He feels strongly that the best intervention is going to be through changing people’s diets, rather than through probiotic or prebiotic supplementation.
“One of the things I worry about [with probiotic or prebiotic supplements] is the dosages necessary to bring about some kind of permanent change,” Chia says. He does admit, however, that getting people to change their eating habits is easier said than done.
Chia’s lab will be sequencing the metagenomes of human stool samples and assembling all the individual genomes within the metagenomes, down to organisms, with 0.5% abundance. The genomes may not be complete, but they should be complete enough to build a metabolic model for each organism. This endeavor requires an enormous amount of sequencing. Chia says
his lab is actually “overdoing it,” until they optimize the sequencing technique.
The group will also be building new computational tools to create more reliable metabolic models from the genomes, then combining the metabolic models into a community metabolic model. The community metabolic model will allow each of the individual microbes to act independently and change in relative abundance—as if they were being monitored in real time.
Through ongoing interaction, Nick Chia and his collaborators are a dynamic model of the boundless advantages of active
university-clinical partnerships in the age of genomic research.
