Columbia Expands Its Microbiome Research

By Christopher Williams

Investigators at Columbia University Medical Center are stepping up efforts to explore the human microbiome, the complex ecosystems of bacteria that inhabit and interact with our tissues and organs. With the recent creation of the CUMC Microbiome Working Group and a new Department of Medicine Microbiome Core Facility, a multidisciplinary community has been organizing to support and cultivate research in this burgeoning field.

Started at Columbia in 2014 by Nitzan Soffer, PhD, a former postdoctoral scientist in the Mailman School of Public Health, and Ryan Demmer, PhD, assistant professor of epidemiology at Mailman, the Microbiome Working Group fosters interdisciplinary conversation on the latest methods in microbiome research. Meeting roughly twice each month, the group hosts seminars by Columbia investigators and speakers from other research institutions and is laying the groundwork for new collaborations.

Scientists from across the medical center now participate in the working group, a feature that has been key to the group’s success so far. “In microbiome research the best collaborations are multidisciplinary,” Dr. Demmer says, “because individual investigators rarely have expertise that transcends the basic, clinical, and population sciences. We’re trying to bring together all of the necessary perspectives.”

Also leading the effort are several young Columbia scientists. Janet Woollen, a PhD candidate in the Department of Biomedical Informatics, organized several seminars and arranged for a curator-guided tour of the American Museum of Natural History’s microbiome exhibit, “The Secret World Inside You.” Recently, two computational biologists from the Department of Systems Biology—postdoctoral scientist Eugenia Lyashenko, PhD, and graduate student Boris Grinshpun—also joined the working group as co-organizers. Their efforts have increased participation by other computational scientists, including several who presented talks focusing on new methods for microbiome research.

Dr. Soffer, who is now a research scientist in industry, says the addition of expertise in computational analysis is an exciting development. “With next-generation sequencing, there’s suddenly an overwhelming amount of microbiome data, and using these data to understand the microbiome requires a strong computer infrastructure and programming skills. These are things that basic biologists typically have a hard time assembling.”

Dr. Lyashenko also sees the working group as an opportunity to enrich the training that computational students and postdocs in the Department of Systems Biology receive. “Our motivation,” she says, “is to offer our students ideas about what questions clinicians are trying to answer in relation to the human microbiome and what kinds of problems they face when trying to analyze data. We want them to learn how they can contribute.”

Physician-researchers at CUMC are increasingly taking part in the working group as well. Gastroenterologist Daniel Freedberg, MD, assistant professor of medicine at CUMC, for example, is a regular attendee who is interested in how the microbiome mediates and responds to the effects of drugs that suppress stomach acid. “It’s always encouraging to hear that people have a lot of the same questions as I do,” he says, “and some of the bioinformatics talks are pushing me to think harder about ways my studies could have greater impact.”

In a large medical center like CUMC, the clinic clearly offers opportunities for gathering the samples that form the basis of human microbiome research. It can also frame urgent health-related questions that the field could help answer. At the same time, however, many clinical investigators do not have the expertise and technical infrastructure to conduct these kinds of studies.

Recognizing the growing interest in microbiome research and need for this kind of support at CUMC, the Department of Medicine recently committed funds to enable the creation of a new Microbiome Core Facility. Leading its development is Anne-Catrin Uhlemann, MD, PhD, assistant professor of medicine and a bacteriologist and infectious diseases specialist. “Although many clinician investigators are studying large cohorts that are relevant for microbiome research,” she explains, “there are some unique considerations that distinguish this type of study from a straightforward epidemiological study. We want to help address these challenges.”

The Department of Medicine Microbiome Core Facility is open to researchers across campus and provides a variety of services. These include guidance on various elements of study design, such as determining sampling requirements and making patient participation in the study more convenient. Because genetic material can be damaged when frozen, the core also offers protocols for collecting, storing, and shipping sensitive stool samples for genetic sequencing. In addition, it can provide assistance with DNA extraction and batch samples from multiple labs to make sequencing more cost-effective for all. In the future, Dr. Uhlemann anticipates that the core could incorporate computational scientists to provide additional assistance with data analysis.

Dr. Uhlemann hopes that the new core and working group will empower investigators across the university to get involved in microbiome research. “Our idea,” she says, “is to enable researchers without a large experimental lab or computational expertise to do large-scale, data-intensive studies.”

Dr. Freedberg expresses an excitement for these developments that all of the working group participants share. “Even with the progress that microbiome research has made,” he says, “we’re in an early, semi-descriptive stage, where even really good studies are just characterizing the composition of the human microbiome. There’s so much work to be done to translate this knowledge into therapies, and I think we are just hitting the tip of the iceberg of the relevant expertise at Columbia.”