Sean C.

Murphy

MD

PhD

Bibliography

Dr. Murphy's work focuses on human malaria infection. Human and animals can be protected against malaria sporozoites challenge by immunization with attenuated Plasmodium sporozoites. The protective responses induced by these immunizations remain largely unknown because it is extremely difficult to simultaneously monitor responses against hundreds of potential antigens.

In collaboration with local and international collaborators, Dr. Murphy studies this complex poly-specific T cell repertoire induced by Plasmodium sporozoites using mouse models of malaria infection and novel high-throughput T cell screening technologies.

A major goal of this work is to identify protective antigens in mice, validate the orthologous antigens in human subjects and develop multi-component subunit vaccines that target the pre-erythrocytic stage of malaria infection. Such vaccines could accelerate the development of effective vaccines for the eradication of malaria.

The development of high-throughput tools for T cell antigen discovery would also have broad implications for other infectious and autoimmune diseases and our group is exploring several such possibilities.

Dr. Murphy also directs a clinical pathology group devoted to molecular diagnosis of malaria infections. This work supports malaria human challenge trials and allows for detection of malaria parasites in human blood up to 3-4 days earlier than by conventional blood smears.

Education & Training

BS, Iowa State University, Ames IA (1999)

Post-Graduate Diploma, University of Cape Town, Cape Town, South Africa (2000)

PhD, Northwestern University, Chicago IL (2006)

MD, Northwestern University, Chicago, IL (2008)

Clinical Pathology, University of Washington, Seattle WA (2011)

Honors

Chief Resident in Laboratory Medicine, University of Washington Medical Center (2009-2010)

Strandjord-Clayson Research Award, Laboratory Medicine, University of Washington (2009)

Paul Strandjord Young Investigator Award with Distinction, Acad. Clinical Physicians/Scientists (2011)

Robert F. & Norma Lee Labbé Endowed Faculty Fellowship, University of Washington (2013)

Invited panelist, WHO Working Group on Molecular Malaria Diagnostic Test EQA (London) (2015-2018)

Research Interests

• Parasitology
• Malaria Vaccines
• Malaria Diagnostics
• Clinical Trials

Related Links

Publications

 

Kublin J, Murphy SC, Maenza J, Seilie AM, Jain JP, Goswami B, Berger D, Spera D, Stein DS, Zhao R, Hackling M, Soon RL, Czartoski JL, Potochnic MA, Duke E, Chang M, Vaughan A, Kappe SHI, Leong FJ, Pertel P. Prince WT. 2021. Safety, pharmacokinetics and causal prophylactic efficacy of KAF156 in a Plasmodium falciparum human infection study. Clin Infect Dis. ciaa952. (https://doi.org/10.1093/cid/ciaa952 [doi.org]). PMID: 32644127.

Wang CYT, Ballard E, Pava Z, Marquart L, Gaydon J, Murphy SC, Whiley D, O’Rourke P, McCarthy JS. 2021. Analytical validation of a real-time hydrolysis probe PCR assay for quantifying Plasmodium falciparum parasites in experimentally infected human adults. Malar J 20:181 (https://doi.org/10.1186/s12936-021-03717-y [doi.org]). PMID: 33838672

Murphy SC, Deye GA, Sim BKL, Galbiati S, Kennedy JK, Cohen KW, Chakravarty S, KC N, Abebe Y, James ER, Kublin JG, Hoffman SL, Richie TL, Jackson LA. 2021. PfSPZ-CVac efficacy against malaria increases from 0% to 75% when administered in the absence of erythrocyte stage parasitemia: a randomized, placebo-controlled trial with controlled human malaria infection. PLoS Pathog. 17(5): e1009594. (https://doi.org/10.1371/journal.ppat.1009594 [doi.org]). PMID: 34048504.

Mwakingwe-Omari A, Healy SA, Lane J, Cook DM, Kalhori S, Wyatt C, Kolluri A, Marte-Salcedo O, Imeru A, Nason M, Ding LK, Decederfelt H, Duan J, Neal J, Raiten J, Lee G, Hume JCC< Jeon JE, Ikpeama I, KC N, Chakravarty S, Murshedkar T, Church LWP, Manoj A, Gunasekera A, Anderson C, Murphy SC, March S, Bhatia SN, James ER, Billingsley PF, Sim BKL, Richie TL, Zaidi I, Hoffman SL, Duffy PE. 2021. Two chemoattenuated PfSPZ malaria vaccines induce sterile hepatic immunity. Nature. 595(7866):289-294. (https://doi.org/10.1038/s41586-021-03684-z [doi.org]). PMID: 34194041.

Hergott DEB, Balkus JE, García GA, Cruz KR, Seilie AM, Masters H, Aveika AA, Iyanga MM; Eyono JNM, Guthrie BL, Murphy SC. 2021. Clustering of subpatent infections in households with asymptomatic rapid diagnostic test-positive cases in Bioko Island, Equatorial Guinea independent of travel to regions of higher malaria endemicity: a cross-sectional study. Malaria J. 20(1):313. (https://doi.org/10.1186/s12936-021-03844-6 [doi.org]). PMID: 34247643

Pal S, Myburgh J, Bansil P, Hann A, Robertson L, Gerth-Guyette E, Ambler G, Bizilj G, Kahn M, Zobrist S, Manis MR, Styke NA, Allan V, Ansbro R, Akingbade T, Bryan A, Murphy SC, Kublin JG, Layton M, Domingo GJ. 2021. Reference and point-of-care testing for G6PD deficiency: Blood disorder interference, contrived specimens, and fingerstick equivalence and precision. PLoS ONE. 16(9):e0257560. (https://doi.org/10.1371/journal.pone.0257560 [doi.org]). PMID: 34543346.

Chang M, Johnson S, Seilie AM, Hergott D, Murphy SC. 2021. Application of dried blood spot sample pooling strategies for Plasmodium 18S rRNA biomarker testing to facilitate identification of infected persons in large-scale epidemiological studies. Malar J. https://doi.org/10.1186/s12936-021-03907-8 [doi.org]). PMID: 34620192.

Glasgow H, Cruz KP, Murphy SC. 2021. Reverse transcription enhances sensitivity of fungal broad-range 28S PCR. Molec Mycol. 60(1):myab061. (https://doi.org/10.1093/mmy/myab061 [doi.org]). PMID: 34878120.

Shaffer D, Kumwenda J, Chen H, Akelo V, Angira F, Kosgei J, Tonui R, Ssali F, McKhann A, Hogg E, Stewart VA, Murphy SC, Coombs R, Schooley R; A5297 Team. 2022. Brief report: no differences between lopinavir/ritonavir and non-nucleoside reverse transcriptase inhibitor-based antiretroviral therapy on clearance of Plasmodium falciparum subclinical parasitemia in adults living with HIV starting treatment (A5297). J Acquir Immune Defic Syndr. 89(2):178-182. (https://doi.org/10.1097/QAI.0000000000002839 [doi.org]). PMID: 34693933.

Watson FN, Shears MJ, Matsubara J, Kalata AC, Seilie AM, Talavera IC, Olsen TM, Tsuji M, Chakravarty S, Sim BKL, Hoffman SL, Murphy SC. 2022. Cryopreserved sporozoites with and without the glycolipid adjuvant 7DW8-5 protect in prime-and-trap malaria vaccination. Am J Trop Med Hyg. 106(4):1227-1236 (https://doi.org/10.4269/ajtmh.21-1084 [doi.org]). PMID: 35226868.

Matsubara J, Chang M, Seilie AM, Murphy SC. 2022. Flow cytometric sorting of infected erythrocytes demonstrates reliable detection of individual ring-stage Plasmodium falciparum parasites by Plasmodium 18S rRNA reverse transcription PCR. Am J Trop Med Hyg. 11:tpmd211226. (https://doi.org/10.4269/ajtmh.21-1226 [doi.org]). PMID: 35405648.

Goswami D, Kumar S, Betz W, Armstrong JA, Haile MT, Camargo N, Parthiban C. Seilie AM, Murphy SC, Vaughan AM, Kappe S. 2022. A Plasmodium falciparum ATP binding cassette transporter is essential for liver stage entry into schizogony. iScience 8;25(5):104224. (https://doi.org/10.1016/j.isci.2022.104224 [doi.org]): PMID: 35521513.

Wilder BK, Vigdorovich V, Carbonetti S, Minkah N, Hertoghs N, Raappana A, Cardamone H, Oliver BG, Trakhimets O, Kumar S, Dambrauskas N, Arredondo SA, Camargo N, Murphy SC, Kappe SHI, Sather DN. 2022. Anti-TRAP/SSP2 monoclonal antibodies can inhibit sporozoite infection and enhance protection of anti-CSP monoclonal antibodies. NPJ Vaccines. 7(1):58. (https://doi.org/10.1038/s41541-022-00480-2 [doi.org]). PMID: 35618791.

Hergott DEB, Owalla TJ, Balkus JE, Apio B, Lema J, Cemeri B, Akileng A, Seilie AM, Chavtur C, Staubus W, Chang M, Egwang TG, Murphy SC. 2022. Feasibility of community at-home dried blood spot collection combined with pooled reverse transcription PCR as a viable and convenient method for malaria epidemiology studies. Malar J 221. (https://doi.org/10.1186/s12936-022-04239-x [doi.org]). PMID: 35836179. PMC9284728.

Kimingi HW, Kinyua AW, Achieng NA, Wambui KM, Mwangi S, Nguti R, Kivisi CA, Jensen ATR, Bejon P, Kapulu MC, Abdi AI, Kinyanjui SM; CHMI-SIKA Study Team (including Murphy SC). 2022. Breadth of antibodies to Plasmodium falciparum variant surface antigens is associated with immunity in a controlled human malaria infection study. Front Immunol. 13:894770. (https://doi.org/10.3389/fimmu.2022.894770 [doi.org]). PMID: 35711446.

Zhu Y, Shen R, Vuong I, Reynolds RA, Shears MJ, Yao Z-C, Hu Y, Cho WJ, Kong J, Reddy SK, Murphy SC, Mao H-Q. 2022. Multi-step screening and composition optimization of lipid nanoparticles for prolonged liver-targeted DNA delivery. Nat Comm 13:4282. (https://doi.org/10.1038/s41467-022-31993-y [doi.org]). PMID: 35879315.

Chakravarty S, Shears MJ, James ER, Rai U, KC N, Murphy SC, Hoffman SL. 2022. Efficient infection of non-human primates with purified, cryopreserved Plasmodium knowlesi sporozoites. Malaria J. 21(1):247. (https://doi.org/10.1186/s12936-022-04261-z [doi.org]). PMID: 36030292.

Flannery EL, Kangwangrangsan N, Chuenchob V, Roobsong W, Fishbugher M, Zhou K, Billman ZP, Martinson T, Olsen TM, Schafer C, Campo B, Murphy SC, Mikolajczak SA, Kappe SHI. Sattabongkot J. Plasmodium vivax latent liver infection is characterized by persistent hypnozoites, hypnozoite-derived schizonts, and time-dependent efficacy of primaquine. Molec Ther 26:427-40. (https://doi.org/10.1016/j.omtm.2022.07.016 [doi.org]).

Murphy SC, Vaughan AM, Kublin JG, Fishbauger M, Seilie AM, Cruz KP, Mankowski T, Firat M, Magee S, Betz W, Kain H, Camargo N, Haile MT, Gibson J, Fritzen E, Hertoghs N, Sather DN, Deye GA, Galbiati S, Geber C, Butts J, Jackson LA, Kappe SHI A genetically-engineered Plasmodium falciparum parasite vaccine provides protection from controlled human malaria infection. Sci Transl Med. 14(659):eabn9709. (https://doi.org/10.1126/scitranslmed.abn9709 [doi.org]). PMID: 36001680.

Saveria T*, Parthiban C*, Seilie AM, Roberts J, Stone BC, Tasch M, Murphy SC. A needle-free, mucosally-delivered spirulina platform Plasmodium falciparum circumsporozoite vaccine provides sterile protection against pre-erythrocytic malaria in mice. npj Vaccines. (https://doi.org/10.1038/s41541-022-00534-5 [doi.org]) (*co-first authors).

Gualdrón-López M, Díaz-Varela M, Zanghi G, Aparici-Herraiz I, Steel RJW, Schäfer C, Cuscó P, Vorada Chuenchob V, Kangwangransan N, Billman ZP, Olsen TM, González JR, Roobsoong W, Sattabongkot J, Murphy SC, Mikolajczak SA, Fernandez-Becerra C, Flannery EL, Kappe SHI, del Portillo HA. 2022. Mass spectrometry identification of biomarkers in extracellular vesicles from Plasmodium vivax hypnozoite infections. Mol Cel Proteom (accepted 8/21/2022)

Owalla TJ, Hergott D, Seilie AM, Staubus W, Chavtur C, Chang M, Kublin JG, Egwang TG, Murphy SC. 2022. Rethinking detection of pre-existing and intervening Plasmodium infections in malaria clinical trials. Front Immunol. (https://doi.org/10.3389/fimmu.2022.1003452 [doi.org])   

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.