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University of Washington School of Medicine
Online News
Vol. 11, No. 8
February 23, 2007
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To view an archived version of Online News on the UW Medicine Web site, visit:
http://www.uwmedicine.org/Global/NewsAndEvents/somnews/index.htm
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This week’s news:
* Top journal Genome Research features UW-led studies on gibbon genome and mechanism for alternative DNA reading
* Cancer cells take on mutator phenotype, becoming much more likely to genetically mutate, according to research presented at annual meeting of American Association for the Advancement of Science
* Shock Center and Seattle Cancer and Aging Program offer pilot grants for research on the process of aging
* Longtime UW faculty member Bruce Gilliland, leading rheumatologist, physician, educator, and administrator, dies at age 75
* UW Medicine Alumni Association Science in the Cinema program to feature "Murderball," award-winning documentary about wheelchair rugby; free event for alumni and donors to be held March 3 in Ballard
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UW-LED STUDIES FEATURED IN THE JOURNAL GENOME RESEARCH
The findings of two UW genome sciences research teams – one studying the genetics of the gibbon, and another examining a mechanism to allow for alternative readings of DNA – were featured in the February issue of the journal Genome Research.
A group led by Philip Green, professor of genome sciences and a Howard Hughes Medical Institute investigator, found a mechanism that may explain genetic diversity and evolution in higher organisms. The genetic tool, known as an alternative promoter, can cause a particular gene to produce more than one kind of protein, or produce the same protein at different times or in different tissues. The alternative promoter helps organisms get additional functions out of one gene, which may explain why a higher organism like a human can have about the same number of genes as a lower organism like a roundworm, yet be far more complex.
Green and his colleagues compared promoters in the human genome to those in the mouse genome, and used a new statistical tool to identify alternative promoters. A promoter tells specialized enzymes where to start reading DNA to produce a particular protein, and an alternative promoter is active at a different time or in a different tissue, or can tell the enzymes to start reading DNA at a different point on the genome.
The researchers found that about 40 percent to 50 percent of human and mouse genes have alternative promoters, which is a larger percentage than previously thought. The data suggest that alternative promoters are critically important to the functioning of higher organisms.
This month's issue of Genome Research also featured a study led by Evan Eichler, associate professor of genome sciences and an HHMI investigator. Eichler and his colleagues examined the scrambling of the genome of the gibbon, a non-human primate. The genomes of humans and other primates closely resemble those of their ancestors, but the gibbon genome seems to have been more rapidly rearranged during the evolution of that species.
The researchers conducted the most detailed study so far of the chromosomal breaks and rearrangements that have changed the gibbon genome over time. Research on this process could help us better understand how evolution affects the genome, and may also explain how these chromosomal changes relate to chromosomal instability associated with cancer and other genetic diseases.
The research team also included scientists at the University of Bari, in Italy; Washington University, in St. Louis; and the Gibbon Conservation Center, in Santa Clarita, Calif.
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CANCER CELLS TAKE ON MUTATOR PHENOTYPE, RESEARCHERS FIND
When cells become cancerous, they also become 100 times more likely to genetically mutate than regular cells, UW researchers have found. The research may explain why cells in a tumor have so many genetic mutations, but could also be bad news for cancer treatments that target a particular gene controlling cancer malignancy.
The research was led by Lawrence Loeb, UW professor of pathology and biochemistry and director of the Gottstein Memorial Laboratories in Pathology. Loeb presented his research Feb. 18 at the meeting of the American Association for the Advancement of Science in San Francisco.
Most types of cancer are believed to begin with a random genetic mutation that makes a normal cell go horribly awry. This is followed by additional mutations, which endow the cancer cells with properties allowing them to grow without normal controls to become a tumor. These mutated genes would be targets for chemotherapy.
Loeb offered an alternative hypothesis: that cancer cells changed to become much more likely to mutate, taking on a "mutator" phenotype. These cells would develop dangerous genetic mutations at a much faster rate than normal cells, which might account for the high number of mutations seen in tumor cells. With the improvement of cancer-genetics technology, Loeb and his colleagues have recently been able to prove this hypothesis. They found that tumor tissue had random mutation rates up to 100 times higher than normal tissue from the same patient.
Unfortunately, these mutator cells may contribute to advanced tumors being protected from therapeutic treatments. A chemotherapy drug may target a particular oncogene, which is a gene that affects the malignancy of a particular cell. But if cancer cells are mutator cells, a single tumor may have cells with many different types of oncogenes and drug-resistant genes. That chemotherapy drug may kill off some of the cancerous cells, but millions of other cells in the tumor will live on. To be effective, a chemotherapy treatment may have to target more than one oncogene – so-called combination chemotherapy.
Loeb believes this research may eventually help physicians determine the stage and malignancy of a tumor by testing the number of its mutations. The more mutations, the further along the tumor may be in its development to malignancy or metastasis.
The work may also lead to a discovery of why cancer cells become mutator cells. If scientists understand what happens in a cancer cell that makes it become a mutator, they might be able to prevent that from happening in other cells, or slow down the mutation rate, which could delay the onset of cancer.
Loeb may be reached at laloeb@u.washington.edu
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PROGRAMS OFFER SUPPORT FOR RESEARCH ON PROCESS OF AGING
Two new funding opportunities are available for people interested in research on the process of aging. Both programs have a March 30 application deadline, and are open to people at or affiliated with the UW or Fred Hutchinson Cancer Research Center (FHCRC).
The Seattle Cancer and Aging Program, a coordination between the UW and the FHCRC to explore the connections between cancer and aging, is offering one-year awards of up to $40,000 for new pilot proposals on cancer and aging. Applications should address one of seven thematic areas: patterns of care; treatment efficacy and tolerance; effects of co-morbidity; prevention, risk assessment, and screening; psychosocial issues and medical effects; palliative and end-of-life care and pain relief; or the biology of aging and cancer. For more information and an application form, visit http://www.fhcrc.org/science/scap/
The UW's Nathan Shock Center of Excellence in the Basic Biology of Aging is funding pilot projects in basic research on the biology of aging. The one-year awards offer up to $35,000 per project. The application may be designed to rapidly pursue a new finding or research opportunity, or to obtain preliminary data that will serve as a basis for a major research grant application. More information and application instructions are available at http://www.uwaging.org under the link "Pilot Application."
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LONGTIME UW FACULTY MEMBER BRUCE C. GILLILAND DIES SUDDENLY AT 75
Longtime faculty member Bruce Gilliland, who served in several leadership positions in the UW School of Medicine, including as acting dean, died suddenly last weekend after a prolonged battle with cancer. He was 75.
Gilliland served on the faculty for nearly 40 years, holding positions such as head of the Division of Rheumatology at the Seattle VA Hospital, program director of the Internal Medicine Residency Program at the UW, head of the Department of Medicine at Pacific Medical Center, and medical director and later director of medical education at Providence Medical Center. He served as associate dean for clinical affairs for several years, and also spent a year as acting dean of the School of Medicine.
Gilliland was a leading rheumatologist who published many significant works in the field. He was named a master of both the American College of Rheumatology and the American College of Physicians, and a laureate of the American College of Physicians for Washington state. He was recognized many times for his outstanding medical education efforts, receiving both the Paul Beeson and Marvin Turck Outstanding Teacher Awards from the Department of Medicine, and two teaching awards from Swedish-Providence Medical Center.
Gilliland was known for his outstanding professionalism in clinical care and medical education, and was well-regarded for his work in building bridges between the medical field and the larger community. He was honored in 2003 with the UW Medicine Alumni Association Lifetime of Service Award.
The son of medical missionary parents, Gilliland was born in Lima, Peru, and raised in Los Angeles. He attended the University of Arizona on a basketball scholarship and subsequently transferred to Occidental College in Los Angeles, where he graduated in 1956 following two years of service in the U.S. Army. He received his medical degree from Northwestern School of Medicine, and completed his internship and residency at the UW School of Medicine. He spent a combined 45 years at the UW as an intern, resident, physician, administrator, and professor.
Gilliland also was known as someone dedicated to balancing his work and his family life. He is survived by Maren Gilliland, his wife of more than 40 years; his daughters, Jean Gilliland Stivers and Anne Marie Gilliland Pickles; his son, John; his brothers, Keith, Vincent, and Victor; and seven grandchildren. A memorial was held for Gilliland on Thursday, Feb. 22, in Seattle, and a School of Medicine memorial service is being planned. Memorial gifts may be made to the Bruce C. Gilliland, M.D. Memorial Fund at the UW School of Medicine. Call 206-543-6806 for more information.
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ALMUNI ASSOCIATION HOSTING SCIENCE IN THE CINEMA EVENT MARCH 3
Science in the Cinema, a free special event for alumni, donors, and other friends of UW Medicine, will feature a screening of the award-winning film "Murderball" at a cinema in Ballard on March 3. In this documentary, world-class, wheelchair-using athletes play no-holds-barred rugby and show how they live with spinal-cord injury. The movie is rated R and is not suitable for children under the age of 17.
The event is sponsored by the UW Medicine Alumni Association, and the film screening will be followed by a discussion with two UW Medicine experts in spinal-cord injury and research: Charles Bombardier, professor of rehabilitation medicine, and Philip Horner, assistant professor of neurological surgery, as well as special guest Clark Landis, who lives with a spinal cord injury.
The event will be held Saturday, March 3, with doors opening and breakfast refreshments served at 8 a.m. and the screening starting at 8:45 a.m. It will be held at the Majestic Bay Theatre in Ballard, 2044 NW Market St., Seattle, Wash. For more information or directions, visit the theatre's Web site at http://www.majesticbay.com or call the theatre at 206-781-2229.
Seating is limited and will be available on a first-come, first-served basis. The Majestic Bay Theatre offers handicap accessibility and hearing-impaired services. Please let the Alumni office know if someone in your party needs special seating. To RSVP for the event, contact the UW Medicine Alumni Association at medalum@u.washington.edu or call 206-685-1875.
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Online News is published by Health Sciences/UW Medicine News and Community Relations.
Justin Reedy, editor:
206-685-0382, jreedy@u.washington.edu
Online News is copyright 2007. All rights, including electronic redistribution, are reserved.
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