Ludmila Prokunina-Olsson, Ph.D.
Laboratory of Translational Genomics
8717 GROVEMONT CIRCLE
GAITHERSBURG MD 20877
Recent genome-wide association studies (GWAS) have identified multiple common germline genetic susceptibility variants that may play a role in a variety of human diseases and outcomes. Dr. Prokunina-Olsson explores the connections between the GWAS-identified genetic susceptibility variants and molecular phenotypes of importance for cancer. Some of her findings resulted in translational and clinical applications.
Genetics of Bladder Cancer
Several GWAS for bladder cancer risk in individuals of European ancestry discovered 15 genomic regions with statistically significant associations. In addition to contributing to GWAS efforts, Dr. Prokunina-Olsson leads the post-GWAS analysis of these regions that includes genetic fine-mapping and functional molecular analysis of the candidate genetic variants and genes. In addition to bioinformatics tools, her lab uses a wide range of experimental tools to explore both coding and non-coding genetic variants, such as DNA and RNA sequencing, genotyping, RNA and protein expression, DNA-protein interaction analysis, genome editing, cell culture, epigenetic studies, etc. She is also exploring the regulation of somatic mutagenesis in bladder tumors by germline variants and environmental factors. So far, she has comprehensively explored and published results of her studies on five of 15 GWAS regions associated with bladder cancer risk; the work on other GWAS regions is ongoing.
Genetics of Infection and Cancer
Recently, Dr. Prokunina-Olsson’s lab has discovered a novel human interferon, IFN-λ4, by performing a follow-up of GWAS findings for clearance of hepatitis C virus (HCV) infection. Chronic HCV is a primary etiological factor for the development of chronic liver disease and liver cancer. Dr. Prokunina-Olsson leads the genetic and functional studies on IFN-λ4 in relation to HCV and several other infections associated with cancer.
Dr. Prokunina-Olsson received an M.Sc. in Molecular Genetics from Moscow State University, Russia, and a Ph.D. in Medical Genetics from Uppsala University, Sweden. During 2005-2008 she was a visiting fellow with Dr. Francis Collins in the Genome Technology Branch of the National Human Genome Research Institute, NIH. Dr. Prokunina-Olsson joined the Laboratory of Translational Genomics of DCEG as a research fellow in June 2008, became a tenure-track investigator in April 2010, and was awarded NIH scientific tenure and promoted to senior investigator in December 2014. Dr. Prokunina-Olsson has been recognized for her research contributions with an NCI Director’s Merit Award, several NCI Innovation and Intramural Research Awards and several awards outside the NIH.
Kohaar I, Porter-Gill P, Lenz P, Fu YP, Mumy A, Tang W, Apolo AB, Rothman N, Baris D, Schned AR, Ylaya K, Schwenn M, Johnson A, Jones M, Kida M, Silverman DT, Hewitt SM, Moore LE, Prokunina-Olsson L. Genetic variant as a selection marker for anti-prostate stem cell antigen immunotherapy of bladder cancer. J Natl Cancer Inst. 2013;105(1):69-73.
Prokunina-Olsson L, Muchmore B, Tang W, Pfeiffer RM, Park H, Dickensheets H, Hergott D, Porter-Gill P, Mumy A, Kohaar I, Chen S, Brand N, Tarway M, Liu L, Sheikh F, Astemborski J, Bonkovsky HL, Edlin BR, Howell CD, Morgan TR, Thomas DL, Rehermann B, Donnelly RP, O'Brien TR. A variant upstream of IFNL3 (IL28B) creating a new interferon gene IFNL4 is associated with impaired clearance of hepatitis C virus. Nat Genet. 2013;45(2):164-71.
Fu YP, Kohaar I, Moore LE, Lenz P, Figueroa JD, Tang W, Porter-Gill P, Chatterjee N, Scott-Johnson A, Garcia-Closas M, Muchmore B, Baris D, Paquin A, Ylaya K, Schwenn M, Apolo AB, Karagas MR, Tarway M, Johnson A, Mumy A, Schned A, Guedez L, Jones MA, Kida M, Hosain GM, Malats N, Kogevinas M, Tardon A, Serra C, Carrato A, Garcia-Closas R, Lloreta J, Wu X, Purdue M, Andriole GL Jr, Grubb RL 3rd, Black A, Landi MT, Caporaso NE, Vineis P, Siddiq A, Bueno-de-Mesquita HB, Trichopoulos D, Ljungberg B, Severi G, Weiderpass E, Krogh V, Dorronsoro M, Travis RC, Tjønneland A, Brennan P, Chang-Claude J, Riboli E, Prescott J, Chen C, De Vivo I, Govannucci E, Hunter D, Kraft P, Lindstrom S, Gapstur SM, Jacobs EJ, Diver WR, Albanes D, Weinstein SJ, Virtamo J, Kooperberg C, Hohensee C, Rodabough RJ, Cortessis VK, Conti DV, Gago-Dominguez M, Stern MC, Pike MC, Van Den Berg D, Yuan JM, Haiman CA, Cussenot O, Cancel-Tassin G, Roupret M, Comperat E, Porru S, Carta A, Pavanello S, Arici C, Mastrangelo G, Grossman HB, Wang Z, Deng X, Chung CC, Hutchinson A, Burdette L, Wheeler W, Fraumeni J Jr, Chanock SJ, Hewitt SM, Silverman DT, Rothman N, Prokunina-Olsson L. The 19q12 bladder cancer GWAS signal: association with cyclin E function and aggressive disease. Cancer Res. 2014;74(20):5808-18.
Onabajo OO, Porter-Gill P, Paquin A, Rao N, Liu L, Tang W, Brand N, Prokunina-Olsson L. Expression of Interferon Lambda 4 Is Associated with Reduced Proliferation and Increased Cell Death in Human Hepatic Cells. J Interferon Cytokine Res. 2015;35(11):888-900.
Middlebrooks CD, Banday AR, Matsuda K, Udquim KI, Onabajo OO, Paquin A, Figueroa JD, Zhu B, Koutros S, Kubo M, Shuin T, Freedman ND, Kogevinas M, Malats N, Chanock SJ, Garcia-Closas M, Silverman DT, Rothman N, Prokunina-Olsson L. Association of germline variants in the APOBEC3 region with cancer risk and enrichment with APOBEC-signature mutations in tumors. Nat Genet. 2016;48(11):1330-1338.