reprinted from Issue 11, Fall 2010 of Frontiers of Medicine (PDF)
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Two fathers with pulmonary disease have inspired two daughters to seek a cure
Ralph Hewett, an entrepreneur who ran a maritime supply business on the San Francisco waterfront, passed away a week before his 95th birthday from complications of chronic obstructive pulmonary disease (COPD). “His doctors at UCSF were terrific to him during the course of his illness, and we wanted to do something to memorialize him,” says his daughter, Cathy Podell. She and her brother, Michael Hewett, decided to establish the Ralph Hewett Research Fellowship in Airway Disease in his memory.
Sheena Kerr, PhD, the inaugural Ralph Hewett Fellow, decided a few years ago that she wanted to use her laboratory research training to develop better treatments for airway diseases like asthma, COPD and chronic bronchitis. In addition to her scientific curiosity, Kerr was personally motivated because her father has COPD. His disease makes it difficult to walk long distances and has caused lung infections requiring hospitalization. “I had never worked in lung biology before, but after reading about his condition, it was something I was interested in,” says Kerr.
For the past year, Kerr has worked with John Fahy, MD, a professor in the Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, discovering what causes people with airway disease to produce extremely thick mucus. “When we look at people who have passed away from asthma, their airways are almost completely blocked with mucus,” says Kerr. “Anything we can do to take thick mucus and make it thinner is very good.”
Mucus is made up of long, centipede-like protein strands called mucins; each “foot” is covered with sugars. Kerr and Fahy have learned that lectins, another type of protein, like to bind to these sugars. Lectins act like a zipper, connecting mucin strands together to create thick, sticky mucus. They found that lectins were far more prevalent in mucus from patients with severe asthma compared with healthy volunteers. They also found that bacteria and fungi which cause infections also produce lectins.
Now they are trying to design a sugar which could mimic the “native” sugars that lectins normally bind to, prevent-ing the lectins from binding to mucin sugars and “zipping” them together. This strategy could lead to development of a drug which prevents thick mucus from forming. The Hewett Fellowship made these initial discoveries possible, and Kerr and Fahy have written grants to continue their research.
“To develop new treatments for intractable problems like mucus plugging, we need to work in a multi-disciplinary way to understand how abnormal mucus forms, then develop logical interventions,” says Fahy.
Fahy says the Ralph Hewett Fellowship supports the development of “disease biologists” who combine expertise in cellular and molecular biology with deep understanding of how a disease affects patients. The fellowship provides time for laboratory-based scientists to develop clinical knowledge of a disease, and for clinician scientists to develop skills in research, including bench research. “By training disease biologists, we’re better placed to suggest new ways of treating diseases,” he says.
The Division of Pulmonary and Critical Care Medicine has one of the largest and most prestigious training programs in the country. The program officially lasts three years, but most scholars train for five to seven years. “In three years, you can go into private practice, but it would be impossible to compete independently in an academic career,” says Stephen Lazarus, MD, who directs the training program.
While a grant from the National Institutes of Health supports the initial training years, funding like the Ralph Hewett Fellowship is vital to helping these outstanding scholars become independent investigators. “The Podells and Hewetts have been very generous in creating this fellowship, which is earmarked for trainees who need another year or two of support to get them to the next level,” says Lazarus. The fellowship can also be used to support international fellows, who are often ineligible for federal grants.
Podell is impressed with what the fellowship has made possible so far. “Sheena is doing some amazing research that could concretely benefit the next generation,” says Podell. “This is something for the future, and we hope to keep this fellowship an ongoing commitment.”
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