Sean Murphy, MD, PhD
Associate Professor, Laboratory Medicine
University of Washington;
Assistant Director, Clinical Microbiology Laboratory
UW Medical Center;
Member, Center for Emerging and Re–emerging Infectious Diseases, University of Washington
Clinical Investigator, Malaria Clinical Trials Center
Medical Director, Human Challenge Center, Center for Infectious Disease Research
Dr. Murphy's work focuses on the immune response to complex infectious diseases and on diagnostic test development. The major focus of the laboratory is malaria infection of humans and animal models by Plasmodium parasites. There is currently no approved vaccine to prevent malaria infection. However, for the past 40 years, it has been known that humans and animals can be protected against later infections when experimentally immunized with repeated doses of attenuated Plasmodium sporozoites, the form of the parasite that is transmitted by female Anopheles mosquitoes. The protective immune responses induced by these kind of immunizations remain largely unknown because it is extremely difficult to simultaneously monitor responses against hundreds of potential antigens. Using novel high–throughput T cell screening technologies developed in collaboration with Dr. Brad Stone, Dr. Murphy’s group studies the complex poly–specific T cell repertoire induced by Plasmodium sporozoites using mouse models of malaria infection. The laboratory is also exploring novel methods to experimentally induce broadly protective immune responses against malaria using synthetic biology–based T cell vaccines.
A major goal of this work is to identify protective antigens in mice, validate the orthologous antigens in human subjects and develop unprecedented multi–component subunit vaccines that target the pre–erythrocytic stage of malaria infection. Such vaccines could accelerate elimination and eventual eradication of malaria, a major goal worldwide. The tools that the Murphy Lab are developing for antigen discovery and vaccination may also find use more broadly for other infectious and autoimmune diseases in need of vaccines and therapeutics. Our group is exploring several such possibilities using small animal models and livestock in an effort to improve both human and livestock health.
In collaboration with Dr. Jim Kublin (Fred Hutch Cancer Research Center) and the Seattle Biomed Malaria Clinical Trials Center (MCTC, http://seattlebiomed.org/mctc), Dr. Murphy helps to conduct controlled human malaria infection (CHMI) studies in Seattle that are aimed at identifying effective malaria drug and vaccine candidates in humans. These Phase I/II studies are used to make early decisions about such candidates prior to initiating larger Phase II/III studies in malaria–endemic regions. The samples obtained in these studies are also used to identify correlates of immunity and to probe for new antigens. The Seattle MCTC center is the only West Coast–based CHMI facility in the U.S. that was purpose–built to conduct these studies. Dr. Murphy serves as a clinical investigator in these studies. In addition, the quantitative reverse transcription PCR (qRT–PCR) assays developed by Dr. Murphy are conducted by the Department of Laboratory Medicine under Dr. Murphy’s direction in support of early diagnosis in these CHMI studies. The qRT–PCR assays supported by UW are recognized as some of the most sensitive and robust molecular diagnostic assays for malaria in the world – the assays allow for detection of malaria parasites in human blood up to 3–4 days earlier than by conventional blood smears. Dr. Murphy’s group is also promoting a quality improvement initiative to implement external quality assurance amongst a network of CHMI centers that perform molecular malaria testing in the U.S., Europe, Africa and Australia.
Dr. Murphy is Assistant Professor of Laboratory Medicine, University of Washington. He is Assistant Director of the clinical microbiology laboratory in Laboratory Medicine at the University of Washington Medical Center, which provides testing for infectious diseases. Dr. Murphy is also a Member of the UW–based Center for Emerging and Re–emerging Infectious Diseases and is a Clinical Investigator with the Malaria Clinical Trials Center at Seattle Biomedical Research Institute.
Representative recent publications
- Stone BC, Kas A, Billman ZP, Murphy SC. 2016. Complex Minigene Library Vaccination for Discovery of Pre-Erythrocytic Plasmodium T Cell Antigens. PLoS ONE.
- Billman, ZP, Kas A, Stone BC, Murphy SC. 2016. Defining rules of CD8+ T cell expansion against pre–erythrocytic Plasmodium antigens in sporozoite–immunized mice. Malaria J. 15(1):238. doi: 10.1186/s12936–016–1295–5.
- Billman ZP, Seilie AM, Murphy SC. 2016. Purification of Plasmodium sporozoites enhances parasite–specific T cell responses Infect Immun. doi: 10.1128/IAI.01439–15.
- Talley AK, Healy SA, Finney OC, Murphy SC, Kublin J, Salas CJ, Lundebjerg S, Gilbert P, Whisler J, Van Voorhis WC, Wang R, Murphy JR, Ockenhouse CF, Heppner DG, Kappe SH, Duffy PE. 2014. Safety and comparability of controlled human Plasmodium falciparum infection by mosquito bite in malaria-naïve subjects at a new facility for sporozoite challenge. PLoS ONE 9(11): e109654. (doi:10.1371/journal.pone.0109654).
- Hodgson SH, Douglas AD, Edwards NJ, Kimani D, Elias SC, Chang M, Daza G, Seilie AM, Magiri C, Muia A, Juma EA, Cole AO, Rampling TW, Anagnostou NA, Gilbert SC, Hoffman SL, Draper SJ, Bejon P, Ogutu B, Marsh K, Hill AVS, Murphy SC. 2015. Increased sample volume and use of quantitative reverse–transcription PCR can improve prediction of liver–to–blood inoculum size in controlled human malaria infection studies. Malaria J 14:33. (doi: 10.1186/s12936–015–0541–6).
[PMC ID: PMC4318195]
- Fang FC, Billman ZP, Wallis C, Abbott A, Olson J, Dhanireddy S, Murphy SC. 2015. Human Diphyllobothrium nihonkaiense infection in Washington State. J Clin Microbiol 53(4):1355–7. (doi: 10.1128/JCM.00065–15).
[PMC ID: PMC4365193]
- Douglass AN, Kain HS, Abdullahi M, Arang N, Austin LS, Mikolajczak SA, Billman ZP, Hume JC, Murphy SC, Kappe SH, Kaushansky A. 2015. Host–based prophylaxis successfully targets liver stage malaria parasites. Mol Ther. 23(5):857–65. (doi: 10.1038/mt.2015.18).
[PMC ID: PMC4427874]
- Murphy SC, Hermsen CC, Douglas AD, Edwards NJ, Petersen P, Fahle GA, Adams M, Berry AA, Billman ZP, Gilbert SC, Laurens MC, Leroy O, Lyke KE, Plowe CV, Seilie AM, Strauss KA, Teelen K, Hill AVS, Sauerwein RW. 2014. External quality assurance of malaria nucleic acid testing for clinical trials and eradication surveillance PLoS ONE 9(5): e97398.
- Murphy SC, Shott JP, Parikh S, Etter P, Prescott WR, Stewart VA. 2013. Malaria Diagnostics in Clinical Trials. Am J Trop Med Hyg. 89(5):824–839.
- Murphy SC, Kas A, Stone BC, Bevan MJ. 2013. A T-cell response to a liver-stage Plasmodium antigen is not boosted by repeated sporozoite immunizations. Proc Natl Acad Sci USA 110(15): 6055–6060.
- Murphy SC, Daza G, Chang M, Coombs RW. 2012. Laser cutting eliminates nucleic acid cross–contamination in dried blood spot processing. J Clin Microbiol. 50(12):4128–30.
- Marvin RG, Wolford JL, Kidd MJ, Murphy SC, Ward J, Que EL, Mayer ML, Penner–Hahn JE, Haldar K, O'Halloran TV. 2012. Fluxes in "free" and total zinc are essential for progression of intraerythrocytic stages of Plasmodium falciparum. Chem Biol. 19(6):731–41. doi: 10.1016/j.chembiol.2012.04.013.
- Murphy SC, Prentice JL, Williamson K, Wallis CK, Fang FC, Fried M, Pinzon C, Wang R, Talley AK, Kappe SHI, Duffy PE, Cookson BT. 2012. Real–time quantitative reverse transcription PCR for monitoring of blood–stage Plasmodium falciparum infections in malaria human challenge trials. Am J Trop Med Hyg. 86(3):383–94.
- Murphy SC, Hoogestraat DR, SenGupta DJ, Prentice J, Chakrapani A, Cookson BT. 2011. Molecular diagnosis of cystoisosporiasis using extended range PCR screening. J Mol Diagn. 13(3):359–62.
- Haldar K, Murphy SC, Milner DA, Taylor TE. 2007. Malaria: mechanisms of erythrocytic infection and pathological correlates of severe disease. Annual Review of Pathology: Mechanisms of Disease. 2: 217–49.
- Murphy SC, Fernandez–Pol S, Chung PH, Murthy SNP, Milne SB, Salomao M, Brown HA, Lomasney JW, Narla M, Haldar K. 2007. Cytoplasmic remodeling of erythrocyte raft lipids during infection by the human malaria parasite Plasmodium falciparum. Blood. 110(6):2132–9.
- Murphy SC, Harrison T, Lomasney J, Hamm H, Mohandas N, Haldar K. 2006. Erythrocyte G protein as a novel target for malarial chemotherapy. PLoS Med. 3(12):e528.
- Murphy SC, Hiller NL, Harrison T, Lomasney JW, Mohandas N, Haldar K. 2006. Lipid rafts and malaria parasite infection of erythrocytes (review). Molecular Membrane Biology. 23(1):81–88.
- Murphy SC, Samuel BU, Harrison T, Speicher KD, Speicher DW, Reid ME, Prohaska R, Low PS, Tanner MJ, Mohandas N, Haldar K. 2004. Erythrocyte detergent–resistant membrane proteins: their characterization and selective uptake during malarial infection. Blood. 103(5):1920–8.
- Murphy SC, Breman JG. 2001. Gaps in the childhood malaria burden in Africa: cerebral malaria, neurological sequelae, anemia, respiratory distress, hypoglycemia and complications of pregnancy. Am J Trop Med Hyg. 64
Last updated: 11/13/2018