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Balancing Our Microbiome

Dr. Kamada focuses on the bad actors of the microbiome—bacterial troublemakers that contribute to IBD pathogenesis.

Health research labs hum with the possibility for wonder and discovery. As a boy growing up in Western Japan, Dr. Nobuhiko Kamada was fascinated by his first experience visiting a lab. His father, a researcher and clinician in obstetrics and gynecology, had invited his son into a captivating new world.

When Dr. Kamada was fourteen, the family joined his father in New York City while he studied at Rockefeller University. As he again trailed his dad into the lab, he firmly imprinted on a future in science research.

Now spanning 20 years, Dr. Kamada’s career has tracked intersecting questions about our gut microbiome in gastrointestinal health and disease. How do bacteria interact with host immunity and each other? What mechanisms disrupt—or promote—a healthy balance?

Targeting The Troublemakers

Trillions of bacteria in our gut perform an ongoing, delicate dance that can be tripped up by infection and disease. When one kind of bacteria is thrown off-kilter, others compensate—with often harmful results. For people suffering from Inflammatory Bowel Disease (IBD), that can mean a negative feedback loop of debilitating flareups.

Dr. Kamada first encountered IBD as a PhD candidate studying bacteria and host interaction. He trained under gastroenterologist and leading researcher, Toshifumi Hibi at Keio University School of Medicine. Dr. Kamada was tasked to examine the impact of beneficial bacteria in the gut.

A fortuitous encounter with Dr. Gabriel Nuñez from the University of Michigan, brought Dr. Kamada back to the US. Dr. Nuñez is known for discovering a pivotal gene mutation associated with Crohn’s disease. He helped Dr. Kamada land a post-doctoral position at the University of Michigan. Four years later, Dr. Kamada secured a faculty position.

We targeted a specific troublemaker associated with Crohn’s disease—adherent-invasive Escherichia coli. We discovered that it chooses a different nutrient when the gut is inflamed and will outcompete the good guys.

Today Dr. Kamada focuses on the bad actors of the microbiome—bacterial troublemakers that contribute to IBD pathogenesis. His target is adherent-invasive Escherichia coli, a pathogenic form of E. coli. It’s known to accumulate in the intestinal mucosa of Crohn’s disease patients and appears to promote intestinal inflammation. Dr. Kamada determined that this particular troublemaker gains a competitive edge over non-pathogenic E. coli by its ability to switch its food source. In a healthy gut, both rely on carbohydrates. When the gut is inflamed, however, adherent-invasive Escherichia coli uniquely adjusts its nutrient preference to the amino acid L-serine.

Identifying L-serine, found in a wide range of dietary proteins, revealed intriguing prospects for diet-based therapies. In 2016, Dr. Kamada’s research was supported by an Innovator Award from the Kenneth Rainin Foundation. With a group of co-authors, he published those findings in a new paper in Nature Microbiology. A 2020 Synergy Award will help build on those advances in collaboration with two University of Michigan colleagues. They aim to validate the effect of modifying dietary L-serine on the microbiome and disease outcomes.

Collaboration with clinicians and researchers in other fields is absolutely necessary to develop treatment strategies. I’m working with an IBD doctor and a dietician right now.

It’s Personal

Dr. Kamada’s career traces some of his closest relationships. Early exposure to his father’s research labs proved a fertile beginning. Drs. Hibi and Nuñez were especially influential mentors and pivotal to the direction his research has taken him.

Dr. Kamada also has a personal connection to the toll that IBD takes on people who suffer from it. As a PhD candidate, he studied alongside Dr. Hiroshi Chinen, who had suffered from Crohn’s disease since middle school. They became close friends, talking late into the night about the inner workings of the gut. In 2012, Dr. Chinen died of rectal cancer associated with Crohn’s disease.

That loss still unmoors Dr. Kamada. Yet the memory of his dear friend and colleague also fortifies his sense of purpose in this work.

A Collective Effort

Dr. Kamada encourages early-career researchers to connect with new people and ideas, and pursue what most inspires and motivates them. These influences will stimulate their research and sustain them in the face of daunting challenges.

It’s very important to meet people in person—speak at a conference, go to dinner with someone. That kind of personal interaction really changed my career path and gave me new opportunities. I met Dr. Mohamed Donia at my first Innovations Symposium and we’re now collaborating.

For Dr. Kamada, the coronavirus pandemic is both a scientific and a personal challenge. Like many of his colleagues, Dr. Kamada is secluded at home in Michigan, writing papers and pursuing grant funding. But he’s eager to return to the work and wonder of his lab. He wants to get back to working side by side with fellow researchers and to nurturing relationships that can unlock groundbreaking solutions.

Much like the pursuit of a cure for IBD, finding our way through this global health crisis is a complex undertaking that will benefit most from our collective effort. The collaborative culture of scientific research—now mobilized worldwide to address the pandemic—is an invaluable model. While so much is shut down, how we open up to each other will make all the difference in the world.

Just ask Dr. Kamada.

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