Shlossman investigates inflammation in cystic fibrosis
Michael Shlossman, MD, a third-year fellow in our pulmonary disease and critical care medicine program, has received a two-year Clinical Fellowship Research Award from the Cystic Fibrosis Foundation. Working in the lab of Daniel Cook, MD, PhD, Shlossman will use the award to investigate why lung inflammation persists in many people with cystic fibrosis despite treatment with highly effective CFTR modulator therapies.
CFTR modulators have transformed care for many people with cystic fibrosis by restoring the function of the faulty CFTR protein. Although these medications improve lung function and overall health, many patients continue to experience chronic inflammation and respiratory symptoms. For years, researchers largely attributed the lingering inflammation to the lasting effects of chronicinfections and lung damage. Shlossman’s research explores the possibility that part of the inflammation may stem from the immune system itself.
“We’re learning more and more that CFTR might be more than a protein that thins mucus and moves ions,” Shlossman said. “It actually appears to be present in T cells, and it may play an intrinsic role in the inflammatory memory of the lungs; there’s evidence starting to point to this being an intrinsic disease of the immune system.”
His work focuses on tissue-resident memory T cells, a long-lived population of immune cells that remain in the lungs after an infection. These cells normally help the body respond more quickly to familiar threats, but Shlossman wants to determine whether CFTR dysfunction can cause them to become overactive. Using preclinical models, the team will also test whether CFTR therapies can directly calm these immune cells once they have become established.
“You can restore CFTR function, but you may still have a population of long-lived immune cells in the lungs that are ready to overreact,” Shlossman said. “That could help explain why many patients don’t get all the way better, even with these remarkable therapies.”
For Shlossman, the fellowship award represents an important step toward a career combining patient care with research. It will provide advanced training in adaptive immunology and airway disease while supporting work that could identify new therapeutic targets for people living with cystic fibrosis.
“Michael brings exactly the kind of curiosity and rigor needed in a physician-scientist,” Cook said. “A Clinical Fellowship Research Award from the Cystic Fibrosis Foundation is a real honor. These are competitive awards, and they recognize fellows with the potential to become leaders in CF research. The idea that CFTR dysfunction might reprogram the immune system’s memory is a genuinely fresh way to think about persistent inflammation in CF. If he’s right, tissue-resident memory T cells could become an entirely new therapeutic target, and I’m excited to help him pursue it.”
Shlossman extends thanks to both Cook and David Stoltz, MD, PhD, Director of the Division of Pulmonary, Critical Care and Occupational Medicine, for their mentorship as he researches a new disease. “Dr. Cook and Dr. Stoltz have really guided me through getting my project started,” he said. “They have been amazing mentors who helped me conceive the project and also coached me through the submission process. I have experience with research in the past, but this is a new disease for me, so their experience and expertise have been especially valuable.”