Michael J. Welsh, MD, a distinguished professor of internal medicine at the University of Iowa, has been awarded the prestigious 2025 Lasker-DeBakey Clinical Medical Research Award for his groundbreaking investigations into cystic fibrosis (CF). Welsh’s pioneering research has been instrumental in unraveling the molecular mechanisms underpinning CF, ultimately catalyzing the development of transformative therapies that have significantly improved the longevity and quality of life for individuals affected by this previously fatal genetic disease.
The Lasker-DeBakey Award, often celebrated as “America’s Nobels,” honors extraordinary achievements in biomedical research with a strong clinical impact. Dr. Welsh shares this year’s honor with Jesús “Tito” González, formerly of Vertex Pharmaceuticals, and Paul A. Negulescu of Vertex Pharmaceuticals. Their collaborative work was vital in the creation of a novel triple-drug combination therapy that has revolutionized the treatment landscape for CF, extending life expectancy and managing symptoms with unprecedented efficacy.
Cystic fibrosis is a hereditary disorder caused by mutations in the CFTR gene, which encodes a protein crucial for the regulation of chloride ion transport across epithelial cell membranes. Proper chloride ion flow maintains the hydration of airway surfaces and facilitates the clearance of mucus that traps pathogens and particulates. CF-causing mutations impair the function of this CFTR protein, resulting in viscous, sticky mucus accumulation, chronic lung infection, and progressive tissue damage.
Welsh’s research deciphered key aspects of CFTR protein function and the detrimental effects of various mutations on chloride conductance. He demonstrated that defective CFTR disrupts ion transport, providing the scientific groundwork that made life-saving therapeutic interventions possible. This fundamental knowledge eventually spawned treatments that have shifted cystic fibrosis from a terminal illness in childhood to a chronic, manageable condition for many.
Starting his career over four decades ago, Welsh’s early investigations focused on airway epithelial ion transport abnormalities in CF patients, a subject that preceded the identification of the CF gene in 1989. His team conclusively established that CFTR functions as an ion channel that permits chloride movement across airway surfaces, a breakthrough that deepened understanding of the disease’s pathophysiology. Moreover, Welsh’s lab made the seminal observation that lowered temperatures could “correct” certain mutant CFTR proteins, hinting at the possibility of pharmacological agents capable of restoring CFTR function.
This pivotal insight gave rise to intensive drug discovery efforts aimed at finding small molecules capable of rescuing dysfunctional CFTR variants. Welsh’s categorical classification of CFTR mutations into mechanistic groups allowed for targeted therapeutic development, as specific drugs could be designed to address distinct functional defects. Vertex Pharmaceuticals, leveraging innovative high-throughput screening technologies initiated in part by González and Negulescu, identified compounds that potentiated or corrected CFTR activity.
The culmination of these efforts was the approval of Trikafta® in 2019, a triple-combination therapy that simultaneously addresses multiple categories of CFTR mutations. This therapy dramatically improves chloride channel function and lung health for roughly 90% of individuals with CF, markedly extending life expectancy from a mid-30s average for those born two decades ago to projections approaching eight decades for newborns today.
Welsh emphasizes that scientific progress of this magnitude rests on multidisciplinary collaboration, institutional support, and sustained funding—both public and private. He underscores the importance of curiosity-driven fundamental science as the foundation from which transformative clinical innovations can emerge. His career is a testament to the power of perseverance and the impact of discovery-driven medicine.
While the advances in CF treatments have been extraordinary, Welsh cautions that challenges remain. Approximately 10% of people with CF harbor mutations that do not yet respond to existing therapies. The scientific community must continue dissecting molecular mechanisms and developing novel interventions tailored to these patient populations, ensuring that no individual is left behind in the quest to conquer cystic fibrosis.
Welsh’s extensive career includes numerous accolades recognizing his contributions to CF research and clinical medicine. Beyond the Lasker Award, he has received honors such as the Steven C. Beering Award, Warren Alpert Foundation Prize, Shaw Prize in Life Sciences & Medicine, the Canada Gairdner International Award, and more. His leadership roles have extended to presidencies of prominent societies and memberships in prestigious academies reflecting his stature as a leading physician-scientist.
An Iowa native, Welsh completed his undergraduate education, medical training, and residency at the University of Iowa, joining its faculty in 1981. He holds numerous academic appointments within the Carver College of Medicine, directing the Pappajohn Biomedical Institute while contributing to multiple departments. His tenure as an investigator at the Howard Hughes Medical Institute spanned decades of high-impact research.
The Lasker Awards themselves embody a rich legacy established in 1945 by Albert and Mary Lasker, visionary advocates of biomedical research. Celebrated annually, the awards recognize exceptional achievements in medical science that advance human health. Recipients are honored with a $250,000 prize at a ceremony held this year in New York City, underscoring the continuing global significance of the biomedical discoveries they celebrate.
Dr. Michael Welsh’s story is one of relentless dedication to understanding disease mechanisms at their most fundamental level and translating those insights into real-world therapies that save lives. His work vividly illustrates the potential of precision medicine and the remarkable outcomes achievable when scientific insight is harnessed with perseverance and collaboration.
Subject of Research: Cystic fibrosis molecular biology and therapeutic development
Article Title: Michael J. Welsh, MD, Awarded 2025 Lasker-DeBakey Award for Pioneering Cystic Fibrosis Research
News Publication Date: 2025
Web References: https://laskerfoundation.org/winners/combined-triple-drug-therapy-for-cystic-fibrosis/
Image Credits: University of Iowa Health Care
Keywords: Cystic fibrosis, CFTR protein, translational medicine, genetic disorders, clinical research, Lasker Award
