Explores mechanisms behind chronic bowel disease

Eduardo Villablanca is studying how the balance between the microflora and the immune system in the gut sometimes is impaired, leading to chronic conditions, such as inflammatory bowel disease (IBD). The aim is to find the mechanisms that disrupt the balance and then attempt to restore it.

Eduardo Villablanca

Dr in Immunology

Wallenberg Academy Fellow 2014

Institution:
Karolinska Institutet

Research field:
Searching for the causes of inflammatory bowel disease (IBD) by studying the balance between tolerance and inflammation in the gastrointestinal tract.

What happens in the gut, doesn’t stay in the gut. Instead, it might have consequences to the entire body, explains Eduardo Villablanca.

“In the gut we have a complex system for information exchange with the surroundings. This system provides instructions to the immune system, and if these instructions are somehow incorrect, immune cells can cause harm either within the gut or elsewhere.”

In his laboratory at Karolinska Institutet in Solna, just north of Stockholm, Eduardo Villablanca and his research team are working to understand what goes wrong in the gut’s immune system when inflammatory bowel diseases (IBD), including ulcerative colitis and Crohn’s disease, occurs.

“It is essential to maintain the so called homeostatic balance between the microflora and the immune system, thus ensuring a healthy gut. When that balance is impaired, disease ensues.”

Tolerance and inflammation

The main goal of Eduardo Villablanca’s research is to understand the balance between tolerance and inflammation in the gut. The plan is to use that knowledge to find the cellular and molecular mechanisms controlling inflammation and immunity and how this breaks down to IBD.

“We want to find out how this balance is established. And how it can be restored if it is damaged, or modify it if necessary.”

As he conducts a tour of the lab, Eduardo Villablanca explains how major technological advances have made it possible to map both the entire gut micro-flora and individual immune cells.

“At Karolinska Institutet and SciLifeLab, to which we are affiliated, we can perform experiments using state-of-the–art technology to tackle these questions.”

Dendritic cells instruct

Eduardo Villablanca comes from Chile, where he studied molecular biotechnology and performed his master thesis in developmental biology. He likes traveling, which led him to Europe and Università Vita-Salute in Milan, when he completed his PhD degree in immunology in 2007.

During his time as a postdoc in the U.S., when he researched at Harvard Medical School in Boston and at the Broad Institute in Cambridge, Massachusetts he developed a growing interest in the immune system of the gastrointestinal tract.

“I studied how vitamin A, which we get from food, gives “dendritic” cells and T-cells signals to induce tolerance in the gut.”

Our immune system comprises two lines of defense: one innate and the other acquired. The special ability of dendritic cells to both activate and control functions of our acquired immune system was discovered 1973 by the U.S. researcher Ralph Steinman. In 2011, he was posthumously awarded the Nobel Prize in medicine for his discovery, which Eduardo Villablanca thinks he richly deserved.

“Dendritic cells play a key role in orchestrating the immune system, by either inducing tolerance or inflammation, when necessary. They read their surroundings and give instructions to other cells, such as T-cells that fight infection.”

Eduardo Villablanca, who moved to Sweden in 2015, is now focusing on the cells that receive instructions from the dendritic cells. He is still interested in questions of diet, and the role of nutrients in the immune system.

“Among other things, I want to find out how western diets affect the balance in the gastrointestinal tract.”

“The funding from the Knut and Alice Wallenberg Foundation enables me to put together a multidisciplinary research team capable of researching entirely new areas. The research we are doing now is right at the cutting edge. Without this support I would probably have gone for more safe cards.”

Zebrafish – a good model

Earlier research has shown that there are 163 mutations in patients with IBD. But so far scientists have not been able to discover how and why these mutations disrupt the homeostatic balance in the gut.

“We are now trying to find new methods that may provide an answer.”

Many researchers are studying the mutations in vitro, i.e. outside the organism in petri dishes. But Eduardo Villablanca explains that a major problem here is that it is hard to translate these findings to in vivo models, where tests are carried out on animals or humans. He perceives a need for ways of combining the two models.

One solution is to use zebrafish. Eduardo Villablanca has been well acquainted with these tiny fish since his studies in Chile.

“They are small and display characteristics that are suitable for testing many things simultaneously, combining high-throughput screening with an in-vivo approach.”

Zebrafish can also be used to test new cell therapies, e.g. to repair damaged tissue. In other experiments mice are more suitable. Ultimately the research findings will also be verified in human beings.

Tweeting science

There has been a fair amount to do during his first year heading a research team, so Eduardo Villablanca has not had much time for Twitter. He usually spends considerable time and energy communicating science, using social media, and also in projects with an artistic dimension.

“Well – recounting and explaining to others what you do, and what you have discovered is one of the most exciting and important things you can do as a researcher. I take every chance I get to communicate science.”

Text Susanne Rosén
Translation Maxwell Arding
Photo Magnus Bergström