Support

Q&A with Hilde Cheroutre

A pioneering scientist

Hilde Cheroutre, Ph.D., Professor and Head of the Division of Developmental Immunology, always felt drawn to nature. Growing up in Belgium, she spent a lot of time combing Belgium’s coastline for shells. “I knew there were 89 different species that you could find,” Cheroutre recalls. “My brother and I spent days and days just walking along the beach to find the last missing species. It took us years but we found them all.” When it was time to enroll at the university, Dr. Cheroutre briefly considered engineering and medicine but ultimately set- tled on biology. However, she wanted more than just an undergraduate degree and decided to pursue a Ph.D.

Initially simply a means to be independent, Dr. Cheroutre’s doctoral thesis would forever change the trajectory of her life and career. As a graduate student, she was part of a team that isolated the gene encoding human gamma interferon, one of the first known proteins with antiviral activity. When she presented her work at an international conference, it made a big splash and she had her pick of offers from renowned scientists to join their labs for postdoctoral training. At a time when most of her colleagues chose to stay closer to home, Dr. Cheroutre went abroad to join Dr. Lee Hood’s lab at Caltech in Pasadena, Calif. She only planned to stay for a few years in the U.S., but things changed.

Dr. Hilde Cheroutre

Today, she runs a very successful lab at La Jolla Institute and has received the prestigious National Institutes of Health (NIH) Pioneer Award, the highest-ranking award given by the NIH to “support individual scientists of exceptional creativity who propose pioneering and highly innovative approaches.” Recently she was also chosen as one of 11 members of the Mucosal Immunology Studies Team, a cooperative research group funded by the National Institute of Allergy and Immunology to break new ground in the understanding of the mucosal immune system.

WHAT IS THE MUCOSAL IMMUNE SYSTEM?
The mucosal immune system is our built-in defense system that operates at the borders of the body, such as the epithelial barrier of the intestine. We are constantly exposed to pathogens but most of the pathogens around us never get a chance to gain entry through these mucosal borders because every second and every moment of the day, the mucosal immune system that operates there prevents the invasion of pathogens. Once pathogens break through that first line of defense, the systemic immune system takes over.

WHY DID YOU DECIDE TO WORK ON THE MUCOSAL IMMUNE SYSTEM WHEN MOST IMMUNOLOGISTS ARE FOCUSED ON THE SYSTEMIC IMMUNE SYSTEM?
During my post-doctoral training I studied a molecule that is important for the immune system and that turned out to be highly expressed in the intestine. This prompted me to further investigate this molecule and led me to start working on the intestinal immune system. All of sudden a whole world opened up for me because the immune system in the gut is so fascinating and fairly unexplored. If you think about it, the intestine is the largest contact surface with the outside environment and most infectious pathogens enter the body through the intestinal epithelium. The immune defense at that border is enormous and very sophisticated. But not only that, compared to the systemic immune system, which functions in a basically sterile environment, the mucosal immune system has to operate in the context of a very
dirty environment.

“All of a sudden a whole world opened up for me because the immune system in the gut is so fascinating and fairly unexplored.”

HOW DOES THE MUCOSAL IMMUNE SYSTEM KNOW WHO IS FRIEND AND WHO IS FOE?
The systemic immune system operates in a sterile environment and the moment something comes in that’s “non-self,” it knows it is bad. The mucosal immune system cannot operate that way and often, in fact, the mucosal immune system provides protection based on recognizing self-molecules.

CAN YOU EXPLAIN?
The epithelium in the gut consists of a single layer of epithelial cells and the cells are designed to absorb “foreign” molecules such as broken-down food. The mucosal immune system that patrols the mucosal border is not “alarmed” by the uptake of these foreign molecules. However, if a pathogen infects the epithelial cell, then it will become stressed and it will induce stress or “danger” proteins. In addition, cellular proteins will become misfolded and all together these dietary proteins and “danger” self-molecules will generate a completely different repertoire of antigens on the surface of the infected epithelial cell. This will alarm the mucosal immune system, which then eliminates that infected epithelial cell regardless of the nature of the pathogen. In that way, the mucosal immune system is able to prevent invasion of a large variety of pathogens because it does not need to recognize each specific pathogen separately.

AS A GRADUATE STUDENT YOU IDENTIFIED HUMAN GAMMA INTERFERON. WHAT LED TO THAT DISCOVERY?
The goal for my Ph.D. study was to find and identify a protein that had antiviral activity. Back then we knew the body had the capacity to identify and destroy virus-infected cells,
but it wasn’t clear how and immunology as we know it today didn’t exist. I would isolate RNA from human spleen cells and divide it into separate pools. Then I would inject them separately into frog eggs, which functioned as an incubator to translate that human RNA into proteins. I then took those proteins and put them on infected cells to see which pool of
RNA molecules encoded proteins that protected the cells and cleared the virus. I then split that pool of RNAs and did the same assay until I had isolated a single RNA that encoded a protein with antiviral activity. And that’s how we found human gamma interferon.

HOW DID IT FEEL TO MAKE SUCH A MOMENTOUS DISCOVERY?
I never thought about the finding itself. I was more interested in understanding how the molecule worked and its application.

WHAT’S YOUR ADVICE TO KEEP YOUR IMMUNE SYSTEM IN SHAPE?
Be happy! If you are unhappy, stressed, or tired it impacts the condition of your immune system enormously. Do things that make you happy, that give you peace and satisfaction, things that relax you whatever they may be. Enjoy life, tend to your garden, enjoy art and music, eat healthy food, get enough sleep, and be active. If you do these things, you help your immune system stay fit. If you want to maintain good health, it is very important to keep your immune system in the
best condition.

WHEN DID YOU DISCOVER YOUR INTEREST IN ARCHITECTURE?
I guess it had always been in me, but I wasn’t aware of it. As a scientist I always have to envision the whole picture, to see where this or that system, mechanism, or cell fits in, ask why would it be, and why would you have self-reactivity as part of mucosal immunity. It requires very three-dimensional thinking and also thinking ahead.

It’s the same with architecture. With architecture you always have to envision what it will look like, how the sunlight will travel across the room throughout the day, what the shadows will look like when the light falls this way or that way. You’re constantly imagining the whole picture and that’s exactly what we do in science. We’re constructing things in our mind to figure out how they work.