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Spurring the body to repair itself

Medicine@Yale, 2017 - Nov Dec


Investigator seeks new pathways toward guiding immune system’s ability to heal and restore

Growing up in Buenos Aires, Argentina’s capital city, Carla V. Rothlin, Ph.D., associate professor of immunobiology and of pharmacology, and her three sisters listened to dinnertime conversations steeped in science. Their mother, a physician, regularly shared dermatological case studies from her practice. Their father, a pharmacology researcher, gave incremental progress updates on his lab.

At age 17, Rothlin had to choose her undergraduate specialization before entering the University of Buenos Aires. She did so without hesitation: biochemistry. “I knew it would give me human-oriented biomedical training,” she says, “and also a solid foundation in mathematics, physics, biology, and medicine.”

She remained there for her doctoral studies, also in biochemistry, and met world-renowned scientist Ana Belén Elgoyhen, Ph.D., who became her advisor and mentor. At the time, Elgoyhen studied the neurobiological mechanisms of how humans hear and comprehend sound. Fascinated, Rothlin decided to focus her dissertation on biochemical mechanisms that tune the sensitivity of the inner ear.

“Let’s say you and I are in a noisy bar, and you want to focus only on what I am saying,” Rothlin says, condensing the complex into an everyday analogy as she very frequently does. “The brain has a way to signal back to the inner ear and tune it.”

Intrigued by neurobiology’s complexity, Rothlin pursued that field for her postdoctoral fellowship at the Salk Institute for Biological Studies in California under the tutelage of Greg Lemke, Ph.D. At the time, Lemke and his lab team were just beginning to better understand how a family of three receptor tyrosine kinases, called TAM receptors, which Lemke had discovered in the 1990s, are linked to the immune system. Rothlin felt drawn to immunology. She enthusiastically embraced the field and mastered its jargon and major tenets.

“When you are surrounded by smart, experienced researchers, you can take on a challenge like that,” says Rothlin, noting that even with that sudden change in career focus, an important constant remained. Research questions into the “mechanisms that regulate the magnitude, duration, and types of responses in the body” have guided her work throughout, including in the immunobiology lab she established when she arrived at Yale in 2009.

In a short time, Rothlin has been recognized for her basic science work within various autoimmune diseases, including asthma, lupus, Crohn’s disease, and colitis. In 2016, the Howard Hughes Medical Institute (HHMI), the Bill & Melinda Gates Foundation, and the Simons Foundation made Rothlin one of their inaugural group of HHMI Faculty Scholars, part of a program to support early-career scientists who pursue primarily basic research projects. “It is a huge honor—a very special thing,” Rothlin says of the award, which included funding to support her lab. “Everything I do is with my lab and this award gives us enthusiasm to continue working on basic science.”

Also in 2016, in a paper published in Science, Rothlin and colleagues identified a receptor called TYR03, located on innate immune cells, that controls the strength of the immune response, and could be a potential drug target for treating allergies.

This past May, Rothlin, Sourav Ghosh, Ph.D., associate professor of neurology and of pharmacology, and colleagues detailed in Science how the presence of the cytokine interleukin 4 (IL4) near a damaged site in the body caused macrophages to release growth factors needed to rebuild tissue (see “Advances”).

After discovering that significant relationship, Rothlin and her team will now focus on understanding exactly how macrophages, considered sentinel cells of the innate immune system, coordinate the healing and rebuilding of damaged tissue. “It’s clear that the molecular program that induces different genes and expression of proteins for macrophages to help with tissue repair is a very different program from the one that drives inflammation, the first line of immune defense,” Rothlin says. To untangle that puzzle is to search for nothing less than how the body heals and rebuilds itself. For Rothlin, it is one more puzzle she wants to solve.

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