Michael Welsh, MD, wins Lasker Award for cystic fibrosis research

(Press-News.org) Michael J. Welsh, MD, University of Iowa professor of internal medicine, has won the 2025 Lasker-DeBakey Clinical Medical Research Award for his fundamental research on cystic fibrosis (CF), which paved the way to new therapies that have transformed the health and life expectancy of people with CF. 

Lasker Awards, sometimes called “America’s Nobels,” are among the world’s most prestigious biomedical and clinical research awards. 

Welsh shares the award with Jesús (Tito) González (formerly, Vertex Pharmaceuticals) and Paul A. Negulescu (Vertex Pharmaceuticals) for their key roles in developing a novel treatment for CF – a triple-drug combination that saves the lives of people with this lethal genetic disease. 

“To win the Lasker-DeBakey Award is an extraordinary achievement, and Mike Welsh is fully deserving of this honor. He is a consummate physician-scientist who has devoted his career to improving patients’ lives through the pursuit of discoveries that make life-saving medicines possible,” says Denise Jamieson, MD, MPH, UI vice president for medical affairs and the Tyrone D. Artz Dean of the UI Carver College of Medicine. “Mike Welsh’s work exemplifies how fundamental science - driven by curiosity, collaboration, and purpose - can lead to transformative innovations and therapies.” 

Cystic fibrosis is an inherited disease that damages the lungs and other organs. It is caused by mutations in a single gene that produces a protein, known as CFTR, which allows chloride ions to move in and out of cells. This flow of chloride ions keeps the surface of the airways hydrated and maintains a protective layer of mucus to capture and flush away germs and other irritants. CF mutations damage the CFTR protein, preventing normal chloride ion flow, which leads to thick sticky mucus, chronic infections, and progressive lung destruction.  

Welsh’s research has been instrumental in understanding the function of this critical CTFR protein and how it is “broken” in CF. This knowledge laid the foundation for life-saving therapies that have transformed CF into a manageable condition. 

Today, around 90% of people with CF are candidates for these therapies, and the changes in patients’ outcomes are remarkable: For patients born between 1999-2003 — before these therapies existed — their average life span was mid 30s. For babies born now, life expectancy may be into their 80s. 

Research paves the road to transformational medicine 

When Welsh was starting his career over 40 years ago, CF was fatal, with most patients dying of lung damage before they reached adulthood. 

This harsh reality was embodied by one young patient Welsh encountered early in his career. Her unrelenting cough, difficult breathing, and the “sweet grape” smell of an insidious lung infection that was destined to shorten her life, left an indelible impression on Welsh. It set him on the path to uncover the root causes of the disease and change the odds in favor of patients like that little girl.  

Knowing that CF increases susceptibility to lung infection and following the scientific leads indicating that CF disrupts the flow of chloride ions in and out of cells, Welsh began to investigate how chloride ions move across airway membranes. 

In a study that preceded the discovery of the CF gene, Welsh and a colleague proved that chloride flow is impaired in CF airways. Following the discovery of the CF gene in 1989, Welsh and his team demonstrated definitively that CFTR is a chloride channel, or pore, at the airway surface that allows chloride ions to flow out of airway cells. In a key discovery, Welsh’s team also showed that the mutated CFTR protein can be “corrected” by cooling the protein down, showing that it might be possible to “fix” the mutated protein in patients.  

This result opened the door to the possibility that a small molecule might be able to achieve the same “fix” as cooling did and set the stage for the drug discovery work done by González and Negulescu, which eventually produced the CF drugs that are in use today. 

Although CF is caused by a single gene, there are hundreds of CF-causing mutations that “break” the protein in different ways to cause disease. Welsh’s team developed a systematic classification scheme that grouped different disease-causing mutations into several categories of defect. 

These classifications provided a roadmap for targeted therapies that could “correct” or “modulate” the activity of different subtypes of mutated CFTR protein. The team at Aurora BioSciences (subsequently bought by Vertex) developed clever screening assays to test thousands of small molecules for ones that could rescue mutated channels and help them work well enough to improve lung health. These molecules were developed into approved drugs, which were then combined to add the fixes together. 

Over decades, this collaborative science culminated in Trikafta®, a triple-drug combination approved in 2019 that transformed CF from a fatal condition into a manageable condition for more than 90% of people with the disease. 

The keys to scientific success 

Welsh is clear about the conditions needed to achieve this type of success in science. First and foremost, it is people — teams of dedicated, curious, determined researchers asking hard questions and challenging the answers until they are right. It is also the university environments that foster creativity and support and train those scientists, and it is the public and private funding that allow teams to investigate the fundamental science needed to create breakthrough therapies. 

“I am incredibly honored to receive this award, but for me it is truly a celebration of our entire scientific enterprise. It’s a celebration of what we do and an acknowledgement of the importance of our collective endeavor to understand how things work and how to use that knowledge to improve people’s lives,” Welsh says. “I set out hoping to have an impact and help people with CF. Where we are now exceeds my hopes. 

“But we are not done yet. There are still around 10% of people with CF who can’t benefit from these treatments. We need to continue our work to find solutions that help those people.” 

About Welsh 

An Iowa native, Welsh received his undergraduate and medical degrees and did his medical residency at the UI. He joined the faculty in the UI Department of Internal Medicine in 1981. He is the Roy J. Carver Professor of Internal Medicine and Molecular Physiology and Biophysics, and director of the Pappajohn Biomedical Institute at the Carver College of Medicine. He also holds faculty appointments in the neurology and neurosurgery departments at the Carver College of Medicine. He was an investigator with the Howard Hughes Medical Institute from 1989 to 2024. 

Over his career, Welsh has received numerous honors for his work on CF, including the Steven C. Beering Award (2017), the Warren Alpert Foundation Prize (2018), the George M. Kober Medal (2020), the Shaw Prize in Life Sciences & Medicine (2022), the Wiley prize (2023), and Switzer Prize (2023), the Canada Gairdner International Award (2025), and the Yergin-New International Prize for Biomedical Research (2025). He was president of the American Society for Clinical Investigation from 1996-to 1997 and has served as president of the Association of American Physicians. He also is a member of the National Academy of Medicine, the American Academy of Arts and Sciences, and the National Academy of Sciences. 

About the Lasker Awards 

Established in 1945 by pioneering biomedical research advocates, Albert and Mary Lasker, the Lasker Awards are now widely regarded as America’s preeminent biomedical research prize. The awards carry an honorarium of $250,000 for each category. They will be presented at a gala ceremony in New York City on Friday, September 19, 2025. More information – including detailed scientific back stories and videos documenting laureates’ achievements – is available at laskerfoundation.org. 

END