Applying her knowledge of mast cells, Devavani Chatterjea discovers link to chronic pain ailment in women

"Never could I have imagined the work I am doing now – not even ten years ago."

- Devavani Chatterjea, PhD, MPH

By Nadine Taylor-Barnes

November 8, 2019

When Devavani Chatterjea, PhD, Immunology 2001, left Genentech to return to a university setting and run her own research lab, she never imagined that she would identify a possible cause of a rare disorder that had puzzled gynecologists for years. As an immunologist with a keen interest in mast cells, Chatterjea approached the problem from her unique perspective, applying her knowledge of these immune system cells to explain the disorder’s inflammatory pain.

“I put two and two together and figured out that this condition could be an immune system disorder,” she said.

As such, she became the first scientist to investigate the involvement of mast cells in the complex pain syndrome called vulvodynia. Chatterjea saw that mast cells, which reside in body tissues and release histamine and other chemicals in inflammatory and allergic reactions, were controlling the immune response -- and therefore the debilitating genital pain -- in this disorder. She also decided to examine the substances that trigger the immune system response to begin with.

Vulvodynia has a mysterious presentation: it causes debilitating genital pain in eight percent of women, ages 18 to 60 years; yet, beyond the pain, there are no other clinical symptoms, and no apparent underlying causes. As such, women‘s complaints are viewed skeptically by the clinical community. Typically, women will struggle for a long time before they receive a correct diagnosis, and, once diagnosed, it is then difficult to find effective treatments. Often, it is treated with pain medications that don’t work.

Chatterjea first learned about vulvodynia soon after joining the Biology Department faculty at Macalester College, in Minnesota. She attended a talk by Bernard Harlow, PhD, a leading epidemiologist, who described the condition and how the risk of developing it was greatly amplified in women suffering from seasonal allergies. Chatterjea, interested in environmental public health, was pursuing a master’s degree at the time.

Chatterjea decided that her lab – with its focus on the role of mast cells in inflammatory and chronic pain – would be the ideal place to investigate the condition. No one had pursued this approach before, and her undergraduate students were more than willing to take on what turned out to be a risky assignment. Chatterjea faced an uphill battle. She had to prove why it was a viable research project, develop the methodology and convince both funding agencies and reviewers that the research would produce publishable findings. The gamble paid off, and Chatterjea received funding from the National Institutes of Health as well as the National Vulvodynia Association, a private foundation dedicated to improving the lives of those living with the condition.

Chatterjea’s students soon discovered that mast cells were accumulating in sensitive genital areas exposed to allergenic chemicals and that there was an accompanying increase in nerves in those affected tissues.

She explained the dynamic. “Mast cells ultimately change the perception of pain,” she said. “First, the T cells increase in the skin, and the mast cells accumulate. The levels of Immunoglobulin E (IgE), a protein that attaches to mast cells, increases. The nerve-rich tissue gets overstimulated, and a vicious cycle of acute pain and long-lasting pain is created.”

Once Chatterjea and her students determined that the immune system’s reaction to chemicals, used in laboratory allergy studies, was causing the pain, they still needed to solve the other half of the equation: what in the real world could trigger the immune system’s response in the first place and set off such a reaction?

They have zeroed in on a suspect – a very common preservative called Methylisothiazolinone (MI), often used in shampoos, moisturizers, baby wipes, sunscreens, and household products. In fact, four years ago, the New York Times reported that MI is known to cause rashes and skin irritations and had been named as “the allergen of the year” by the American Contact Dermatitis Society in 2013. That same year a European scientific committee for consumer safety advised that it should not be used in personal products applied to the body. Currently, in the European Union, MI is banned from any use in cosmetics and lotions left on the skin.

Chatterjea’s lab has been working on investigating whether exposure to methylisothiazolinone can cause allergic reactions and subsequent genital pain in mice. Through these studies, they hope to identify biomarkers and therapeutic targets that can be used to develop better classification, management and treatment strategies for patients suffering from allergy-associated vulvodynia.

"Studying anything that sparks my interest"

When asked about what brought her to this point in her research career, Chatterjea credits many things: her education -- undergraduate at Mount Holyoke College; graduate work and postdoctoral training at Stanford; her work in drug development for autoimmune diseases at Genentech; her role as a biology professor and principal investigator at Macalester that included work on a HIV clinical trial as part of a multi-disciplinary team of scientists and physicians in Uganda.

“I have always been open to studying anything that sparks my interest,” Chatterjea said and then offered proof. “I studied mangroves, sparrows, sea urchins, and fruit flies as an undergraduate. At Stanford, I studied tunicates, a marine invertebrate, and later T cells and mast cells, in both mice and people, in Steve’s lab,” she said referring to Stephen Galli, MD, her Stanford mentor. She also credits Galli for helping jump-start her mast cell research at Macalester. “When our project was in its early days, we didn’t yet have the facilities to inject mast cell-deficient mice with mast cells,” she said. “Steve came to our assistance, had his graduate students perform the procedures in the Stanford lab, and then sent the mice to us in Minnesota!”

“I love the complexity of biology, and how one has to think across many scientific disciplines in order to solve these intractable problems. Never could I have imagined the work I am doing now – not even ten years ago.” And now she is the proud mentor of over 100 undergraduate researchers helping them pursue careers in research and medicine.”

Looking into the future, Chatterjea surmises her work may have even broader implications for pain research, “Mast cell accumulation may be a biomarker for other instances of chronic pain,” she said. “Perhaps they can serve as a therapeutic target.”

One thing is for certain -- many women, suffering from vulvodynia, now have Chatterjea and her students to thank for helping to alleviate their pain.