Q&A With Dr. Duane Wesemann, FARE Investigator in Food Allergy
Duane Wesemann, MD PhD, is an assistant professor of medicine at Harvard Medical School and a principal investigator in the Division of Rheumatology, Immunology and Allergy at the Brigham and Women’s Hospital in Boston. He received a New Investigator in Food Allergy award from FARE in 2015. Dr. Wesemann’s research has advanced our understanding of how interactions between the gut and its population of microbes can impact antibody production. He will be presenting his findings at the 2018 FARE Research Retreat, which will be held April 13-14 in McLean, VA.
What first attracted you to food allergy research?
I study antibody development in the lining of the gut to uncover how environmental exposures might shape which antibodies are made. Antibodies, also called immunoglobins – or Ig, for short – are protective proteins that recognize pathogens (disease-causing microbes) and bind very tightly to them. There are many types of antibodies, such as IgM, IgG and IgA. Food allergy happens when a special type of antibody, IgE, recognizes and binds tightly to food proteins. Other types of antibodies that bind food proteins don’t cause food allergy. This raises compelling questions for me. Why do B cells – the cells that make antibodies – produce antibodies that bind to a food protein instead of a pathogen? Why does a B cell that makes antibodies against food protein start making IgE antibodies that cause food allergy? And, finally, why do some people get food allergies while others do not?
What has sustained your interest?
As a physician in an allergy/immunology clinic, I see a variety of patients. While we don’t fully understand diseases like asthma, we can offer a variety of treatments, but in the case of food allergy, our knowledge and treatments are wholly inadequate. It’s surprising how little we know about how and why food allergies arise in certain individuals. It is fully unfair. My patients inspire me to merge my scientific and clinical interests. I feel fortunate that funds from FARE have enabled my laboratory to move into this field of research.
What experimental finding has surprised you the most, and why?
We began by asking whether microbes that live in the gut without causing harm (commensal microbes) can influence what antibodies “see.” We wanted to assess whether antibodies on the surfaces of B cells can recognize the contents of the gut. We also developed tools to culture single B cells and learn what the antibodies they release into their surroundings can recognize. Working in mice, we found that commensal microbes provide a stimulus to newly made B cells that enriches antibody recognition of the contents of the intestines. We expected that any changes the commensal microbes might make to the antibody repertoire – the set of antibodies produced – would be seen only in B cells in the intestine. Instead, we found that commensal microbe-dependent changes to the antibody repertoire were found throughout the mouse body. We were also surprised to learn that these changes occur in the neonatal period but not in adulthood, suggesting some early window of opportunity for commensal microbes to influence antibody repertoires. It’s not apparent how these changes can occur throughout the body and why they occur only in early life.
How might your FARE-supported research affect patient care in the future?
The main drive for this research is to gain fundamental insights into how antibody repertoires are developed. I believe that tackling the problem of food allergy requires both empiric and deductive research. Empiric research tests approaches that can benefit patients even if we don’t understand the underlying mechanisms. An example is oral desensitization. Studies in this area show promise and should be pursued, but the core idea is over 100 years old, with incremental advances. The value my lab can provide to future patient care is in deductive research. We seek to understand the core mechanisms that underlie how and why food allergy develops. By shedding light on what we don’t yet know, this research can reveal truly novel ways to prevent and treat food allergy. While deductive research takes considerable effort and time, we feel it is worth it.
What unresolved question relating to food allergies would you most like to see answered?
So far, our research shows that (A) commensal microbes can influence what antibodies recognize and (B) this influence is apparent early in life. These results suggest that microbe-dependent influences on antibody repertoire may play a role in susceptibility to food allergy. Our future research plans focus on how IgE antibodies that bind food proteins are induced, maintained and resolved. In addition to funds for research, the FARE Investigator award has provided opportunities to interact with other scientists interested in food allergy. Through this, we’ve developed collaborative research efforts to fill gaps in our knowledge in an effort to uncover transformative knowledge.