Titles
- Associate Professor of Lab Medicine and Pathology
Linked information
- rrisques(at)u.washington.edu
Departments
Roles
BMHA Executive Committee, BMHA Training Faculty, HALO Faculty
Genomic instability, cancer and aging
The main focus of Dr. Risques’ research is the study of the molecular mechanisms that link genomic instability and aging. The main molecular alterations that her lab studies are telomere shortening, mitochondrial dysfunction, and age-related accumulation of somatic mutations. She has published on comparative analyses of aging relating telomere length in species with dramatically different lifespans [1,2] and in humans [3]. She has also published evidence that mitochondrial alterations play a role in the progression to cancer in ulcerative colitis (an inflammatory bowel disease that displays features of accelerated colon aging) [4,5]. Subsequently, she obtained R01 funding to develop mitochondrial biomarkers for early cancer detection in this disease. In collaboration with Dr. Kennedy, she has recently applied Duplex Sequencing, the most accurate sequencing technology to date, to the analysis of TP53 mutations, their age-associated increase, and their use in early cancer detection and risk assessment [6]. Interestingly, she discovered that mutations in this cancer-associated gene are found at a very low frequency in most individuals, but increase with age [7,8]. At the Risques lab, we use ultra-deep sequencing to study how somatic mutations accumulate with aging and how they contribute to cancer development. In addition to somatic mutations, we are also interested in other genetic alterations that contribute to aging and cancer including telomere shortening and mitochondrial dysfunction. Our goal is to explore the link between aging and cancer and to investigate the genetic alterations that drive the early steps of human carcinogenesis in order to design better tools for early cancer detection, prediction, and risk assessment. Areas of interest: somatic evolution, aging and cancer, early cancer detection
1. Risques RA, Promislow DEL (2018) All’s well that ends well: why large species have short telomeres Philos Trans R Soc Lond B Biol Sci 373 doi:10.1098/rstb.2016.0448
2. Cerchiara JA, Risques RA, Prunkard D, Smith JR, Kane OJ, Boersma PD (2017) Magellanic penguin telomeres do not shorten with age with increased reproductive effort, investment, and basal corticosterone Ecol Evol 7:5682-5691 doi:10.1002/ece3.3128
3. Glei DA, Goldman N, Weinstein M, Risques RA (2015) Shorter Ends, Faster End? Leukocyte Telomere Length and Mortality Among Older Taiwanese J Gerontol A Biol Sci Med Sci 70:1490-1498 doi:10.1093/gerona/glu191
4. Ussakli CH, Ebaee A, Binkley J, Brentnall TA, Emond MJ, Rabinovitch PS, Risques RA (2013) Mitochondria and tumor progression in ulcerative colitis Journal of the National Cancer Institute 105:1239-1248 doi:10.1093/jnci/djt167
5. Baker KT et al. (2019) Mitochondrial DNA Mutations are Associated with Ulcerative Colitis Preneoplasia but Tend to be Negatively Selected in Cancer Molecular cancer research : MCR 17:488-498 doi:10.1158/1541-7786.MCR-18-0520
6. Kennedy SR et al. (2014) Detecting ultralow-frequency mutations by Duplex Sequencing Nat Protoc 9:2586-2606 doi:10.1038/nprot.2014.170
7. Risques RA, Kennedy SR (2018) Aging and the rise of somatic cancer-associated mutations in normal tissues PLoS Genet 14:e1007108 doi:10.1371/journal.pgen.1007108
8. Krimmel JD et al. (2016) Ultra-deep sequencing detects ovarian cancer cells in peritoneal fluid and reveals somatic TP53 mutations in noncancerous tissues Proc Natl Acad Sci U S A 113:6005-6010 doi:10.1073/pnas.1601311113
