Werner syndrome, a rare disease that mimics premature aging, affects 1 in 50,000 people. Understanding its underlying biology may help researchers better understand cancer biology.
“These people look much older than they are, and this is also true in terms of clinical disease,” says Dr. Ray Monnat, professor of pathology and adjunct professor of genome sciences. “There must be underlying biology in this disease that somehow intersects with aging in a broad sense, and age-associated disease processes including cancer, vascular disease, diabetes, osteoporosis, infertility — a whole host of things that have an age-dependent risk.”
Werner syndrome is caused by a single gene mutation. Medical researchers first described Werner syndrome in the beginning of the 20th century, but interest faded because it occurred so infrequently in Western populations.
In 1966 the UW’s Dr. Arno Motulsky, emeritus professor of medicine, and Dr. George Martin, professor of pathology, published a seminal paper on Werner syndrome that reinvigorated research on the disease. Martin went on to characterize genetic instability in Werner patients and their cells, which may have a role in the risk of developing many diseases, particularly cancer. Further research has also indicated that two other syndromes, Bloom syndrome and Rothmund-Thomson syndrome, overlap with Werner syndrome in terms of biology and the types of tumors that they produce.
“The thing that’s most important for cancer biology is an understanding of how these diseases happen,” says Monnat. “The basic idea is that loss of a protein function leads to genetic instability either during development or in adult life, and this gets you into trouble in several ways.”
Recently Monnat and other researchers have uncovered an important function of the Werner syndrome protein, and how loss of function leads to genetic instability. They have also uncovered evidence suggesting that having a single mutant copy of the Werner gene may elevate a person’s risk of disease. When people with single mutant copies are in the population, they don’t have the outward appearance of any syndrome, but they could have greater risk of developing cancer. A group in New York recently published a paper suggesting that carriers of single mutant copies of the related BLM or Bloom syndrome gene have a two-fold increased risk of colorectal cancer.
“A disease like colorectal cancer is very common,” says Monnat. “Without looking for it, would you have seen this association? Better understanding the biology behind Werner syndrome might give us clues to the origin, diagnosis and treatment of many types of cancer.”
Monnat received a M.D. from the University of Chicago Pritzker School of Medicine in 1976. He completed a residency in anatomical pathology at the UW and affiliated hospitals in Seattle from 1976 to 1980. From 1980 to 1984 Monnat completed a postdoctoral fellowship with Dr. Lawrence Loeb at the Joseph Gottstein Memorial Cancer Research Laboratory at the UW.
Since 1982, Monnat has been a faculty member in the Department of Pathology and an attending pathologist at the UW and Harborview Medical Centers. Among numerous awards, in 1991 Monnat received an Outstanding Teaching Award, and in 1997 won the Exemplary Leadership in Teaching Award, both from the UW School of Medicine.
