University of Iowa professor and EHSRC Member Michael J. Welsh, MD, has won the 2022 Shaw Prize in Life Science and Medicine together with Paul A. Negulescu, senior vice president and site head for San Diego research with Vertex Pharmaceuticals Inc.
The prize was awarded for landmark discoveries of the molecular, biochemical, and functional defects underlying cystic fibrosis and the identification and development of medicines that reverse those defects and can treat most people affected by this disorder.
The Shaw Prize is considered one of the most internationally prestigious awards in science and its application, and it carries a shared monetary award of $1.2 million. It honors individuals who have made “discoveries in the biomedical sciences and innovations in clinical medicine that have led to significant victories in our longstanding war against illness and suffering.” Welsh and Negulescu will receive the prize in fall 2022.
Welsh is a professor in the UI Department of Internal Medicine and its pulmonary, critical care, and occupational medicine division. He also is a professor in the neurosurgery, neurology, and molecular physiology and biophysics departments. Welsh also serves as director of the Pappajohn Biomedical Institute at Iowa. He has been leading groups of scientists studying lung biology and cystic fibrosis (CF) for 40 years.
Brooks Jackson, MD, vice president for medical affairs and the Tyrone D. Artz Dean of the UI Roy J. and Lucille A. Carver College of Medicine, says Welsh’s steadfast pursuit of answers to the fundamental questions underlying cystic fibrosis disease has never wavered in that time.
“As a physician-scientist, Dr. Welsh has remained focused on how his work in the lab would improve the medical care he and colleagues could offer their patients,” Jackson says. “His commitment to discovery and innovation has dramatically changed the lives of people with CF.”
Working with colleagues from the University of California, San Francisco, in the mid-1980s, Welsh first demonstrated that CF disrupts chloride ion movement across the sheet of cells that line the lung’s airways. Chloride, a component of salt, is present in secreted body fluids such as sweat, saliva and mucus, which are vital for the proper function of organs. In the lungs of people with CF, these secretions become thick and elastic and, rather than acting to clear inhaled matter from the lungs, they clog the passageways. Affecting more than 80,000 people worldwide, CF was long considered a lethal disease in childhood. Today, Welsh can point to young people with CF who compete in varsity-level athletics. Life expectancy and health have increased dramatically thanks in part to discoveries made by Welsh and Negulescu.
After the identification of the cystic fibrosis transmembrane conductance regulator (CFTR) gene in 1989, Welsh and his team made key discoveries toward understanding the role the product of this gene—the CFTR protein—plays in allowing chloride to move in and out of cells. They showed how mutations in the gene and the CFTR protein cause cells to malfunction and fuel disease development. Importantly, they showed that defects in the mutated CFTR can be repaired in cells. These insights provided a roadmap for the subsequent quest toward targeted therapies to repair the function of the CFTR protein.
Building on these key discoveries, a team of scientists at Vertex, led by Negulescu, initiated research in 1998 into compounds that modulate the function of the CFTR protein. The research led to the development in 2012 of the first compound that corrects the underlying protein defect responsible for disease symptoms. The drug restored cells’ ability to transport chloride and ushered in a new era of CF treatment, sparking the development of combination-drug therapies.
“The combined contributions of Welsh and Negulescu represent the complete biomedical arc from basic discovery to application to the saving of lives,” said the Shaw Prize in Life Science and Medicine selection committee in announcing the shared award.
Welsh was quick to share the credit for this work.
“I am honored to receive this award, which would not have been possible without so many other people who contributed: terrific mentors, talented and creative students and trainees, my tireless and innovative assistants, my cherished colleagues,” he says. “The support and environment of the University of Iowa made this possible. The Cystic Fibrosis Foundation, National Institutes of Health, Howard Hughes Medical Institute, Carver Trust, and Pappajohn Biomedical Institute provided crucial support along the way. I am deeply grateful.”
The Shaw Prize consists of three annual awards: the Prize in Astronomy, the Prize in Life Science and Medicine, and the Prize in Mathematical Sciences. The award is managed and administered by The Shaw Prize Foundation, based in Hong Kong.
This article was first published by the University of Iowa College of Medicine