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Melissa Barrow, PhD

Instructor, Pathology & Immunology

Phone314-747-4603

Emailmelissa.barrow@wustl.edu

Education

  • BSc in Biochemistry, First Class Honors: University of Queensland, Brisbane, Australia (1998)
  • PhD in Structure Biology: University of Queensland, Brisbane, Australia (2003)

Research Interests

My current research catalogues the humoral response to human pathogens including Flaviviruses (Zika, Dengue, Japanese Encephalitis Virus) and Alphaviruses (Chikungunya) in order to categorize antibody responses as protective, non-protective or exacerbating infection. To do this, I employ a toolbox of low resolution (antigen domain mapping, mutagenesis) and high resolution tools (atomic resolution 3-D structures of antigen-antibody complexes) to identify the molecular signature of antibodies on their target antigen (epitope). The goal is to identify epitopes that correlate with protection and to engineer these as immunogens to elicit a focused antibody response avoiding the pitfalls associated with non-protective antibodies (auto-reactive antibodies, antibody-dependent exacerbation of disease). The overarching aim is to aid vaccine development for the aforementioned important human pathogens.

My work has involved developing robust protocols to express and purify a diverse array of antigens (several of which have been licensed to the biotech industry), and is reliant on close collaboration with the Diamond lab to develop panels of antibodies in order to characterize the mechanism of action for these antibodies in vivo.

Editorial Responsibilities

2016 ad hoc reviewer J Virol

Service to the University

2012 BIO5456 Class – lecturer on the fundamentals of ‘Small-Angle X-ray Scattering

Publications

Fox JM, Long, F, Edeling MA, Lin H, van Duijl-Richter MK, Fong RH, Kahle KM, Smit JM, Jin, J Simmons G, Doranz BJ, Crowe JE Jr, Fremont DH, Rossmann MG, Diamond MS: Broadly Neutralizing Alphavirus Antibodies Bind an Epitope on E2 and Inhibit Entry and Egress. Cell 2015; 163(5):1095–1107 (no. of citations 3)
Edeling MA, Diamond MS, Fremont DH: Structural basis of Flavivirus NS1 assembly and antibody recognition. Proc Natl Acad Sci USA   2014; 111(11):4285-4290. PMCID: PMC3964132 (no. of citations 11)
Edeling MA, Austin SK, Shreshtha B, Dowd KA, Mukherjee S, Nelson CA, Johnson S, Mabila MN, Christian EA, Rucker J, Pierson TC, Diamond MS, Fremont DH: Potent Dengue virus neutralization by a therapeutic antibody with low monovalent affinity requires bivalent engagement. PLoS Pathog 10(40):e1004072. PMCID: PMC3990716 (no. of citations 5)
Lee PD, Mukherjee S, Edeling MA, Dowd KA, Austin SK, Manhart CJ, Diamond MS, Fremont DH, Pierson TC: The Fc region of an antibody impacts the neutralization of West Nile viruses in different maturation states. J Virol   2013;87(24):13729–13740. PMCID: PMC3838241 (no. of citations 5)
Pal P. Dowd KA., Brien JD. Edeling MA, Gorlatov S. Johnson S, Lee I, Akahata W, Nabel GJ, Richter MK, Smit JM, Fremont DH, Pierson TC, Heise MG, Diamond MS: Development of a highly protective combination monoclonal antibody therapy against Chikungunya virus. PLoS Pathog   2013;9(4):e1003312. (no. of citations 38) PMCID: PMC3630103
Jackson LP, Lewis M, Kent HM, Edeling MA, Evans PR, Duden R, Owen DJ: Molecular basis for recognition of dilysine trafficking motifs by COPI. Dev Cell   2012;23(6):1255-1262. (no. of citations 24). PMCID: PMC3521961
Austin SK, Dowd KA, Shrestha B, Nelson CA, Edeling MA, Johnson S, Pierson TC, Diamond MS, Fremont DH: Structural basis of differential neutralization of DENV-1 genotypes by an antibody that recognizes a cryptic epitope. PLoS Pathogens   2012;8(10):e1002930. (no. of citations 37). PMCID: PMC3464233
Youn S, Li T, McCune BT, Edeling MA, Fremont DH, Cristea IM, Diamond MS: Evidence for a genetic and physical interaction between nonstructural proteins NS1 and NS4B that modulates replication of West Nile virus. J Virol 2012;86(13):7360-7371. (no. of citations 39). PMCID: PMC3416313
Shreshtha B, Brien JD, Sukupolvi-Petty S, Austin SK, Edeling MA, Kim T, O’Brien KM, Nelson CA, Johnson S, Fremont DH, Diamond M: The development of therapeutic antibodies that neutralize homologous and heterologous genotypes of dengue virus type 1. PLoS Pathogens 2010;6(4):e1000823. (no. of citations 107). PMCID: PMC2848552
Edeling MA*, Sanker S, Shima T, Umasankar PK, Höning S, Kim HY, Davidson LA, Watkins SC, Tsang M, Owen DJ, Traub LM: Structural requirements for PACSIN/Syndapin operation during Zebrafish embryonic notochord development. PLoS ONE 2009;4(12):e8150. (*Joint first author) (no. of citations 26). PMCID: PMC2780292
Pryor PR, Jackson L, Gray SR, Edeling MA, Thompson A, Sanderson CM, Evans PR, Owen DJ, Luzio JP:   Molecular basis for the sorting of the SNARE VAMP7 into endocytic clathrin-coated vesicles by the ArfGAP Hrb.   Cell 2008;134(5):817-827. (no. of citations 77) PMCID: PMC2648964
Edeling MA, Mishra SK, Keyel PA, Steinhauser AL, Collins BM, Roth R, Heuser JE, Owen DJ, Traub LM: Molecular switches involving the AP-2 beta2 appendage regulate endocytic cargo selection and clathrin coat assembly. Dev Cell   2006;10(3):329-342. (no. of citations 99). PMID: 16516836
Edeling MA, Smith C, Owen D: Life of a clathrin coat: insights from clathrin and AP structures. Nat Rev Mol Cell Biol 2006;7(1):32-44. (no. of citations 135). PMID: 16493411
Bowers K, Piper SC, Edeling MA, Gray SR, Owen DJ, Lehner PJ, Luzio JP: Degradation of endocytosed epidermal growth factor and virally ubiquitinated major histocompatibility complex class I is independent of mammalian ESCRTII. J Biol Chem 2006;281(8):5094-5105. (no. of citations 121). PMID: 16371348
Mishra SK, Keyel PA, Edeling MA, Dupin AL, Owen DJ, Traub LM: Functional dissection of an AP-2 beta2 appendage-binding sequence within the autosomal recessive hypercholesterolemia protein. J Biol Chem 2005;280(19):19270-19280. (no. of citations 45). PMID: 15728179
Heras B, Edeling MA, Schirra HJ, Raina S, Martin JL: Crystal structures of the DsbG disulfide isomerase reveal an unstable disulfide.   Proc Natl Acad Sci USA   2004;101(24):8876-8881. (no. of citations 65) PMCID: PMC428440
Edeling MA, Ahuja U, Heras B, Thöny-Meyer L, Martin JL: The acidic nature of the CcmG redox-active center is important for cytochrome c maturation in Escherichia coli. J Bacteriol   2004;186(12):4030-4033. (no. of citations 15). PMCID: PMC419958
Heras B, Edeling MA, Byriel KA, Jones A, Raina S, Martin JL: Dehydration converts DsbG crystal diffraction from low to high resolution.   Structure   2003;11(2):139-145. (no. of citations 57). PMID: 12575933
Edeling MA, Guddat LW, Fabianek RA, Thöny-Meyer L, Martin JL: Structure of CcmG/DsbE at 1.14 A resolution: high-fidelity reducing activity in an indiscriminately oxidizing environment. Structure 2002;10(7):973-979. (no. of citations 58). PMID: 12121652
Edeling MA*, Guddat LW, Fabianek RA, Halliday JA, Jones A, Thöny-Meyer L, Martin JL: Crystallization and preliminary diffraction studies of native and selenomethionine CcmG (CycY, DsbE). Acta Crystallogr D Biol Crystallogr. 2001;57(Pt 9):1293-1295. (*Joint first author) (no. of citations 10). PMID: 11526323


Lab Phone: 314-747-4603
Office Location: CSRB, Room 7712