Daved H. Fremont, Ph.D.

Professor
Pathology and Immunology
Biochemistry and Molecular Biophysics

Biochemistry, Biophysics, and Structural Biology Program
Immunology Program
Molecular Microbiology and Microbial Pathogenesis Program

  • 314-255-6171

  • 314-747-4546

  • 314-362-8888

  • 8118

  • 7701 Clinical Sciences Research Building

  • fremont@wustl.edu

  • http://pathology.wustl.edu/~fremontlab

  • immunology, virology, structural biology, viral immune evasion, cytokine receptors, signaling, protein trafficking

  • Mechanisms of host immunity and viral evasion

Research Abstract:

Our research group is focused on understanding surveillance processes of the immune system, and the sabotage mechanisms used by pathogens to evade detection and host-mediated elimination. We use the techniques of protein biochemistry, x-ray crystallography and computational biology to determine the three-dimensional structures of proteins and investigate their macromolecular interactions. Current interests of the lab include proteins associated with classical MHC antigen processing and presentation pathways, non-classical MHC family members, and natural killer cell activating and inhibitory receptors. We also actively studying a number of virally encoded proteins that enable host immune evasion. Large-DNA viruses (i.e. herpesviruses and poxviruses) have evolved a myriad of strategies that include the sabotage of antigen processing, the molecular mimicry of host signaling molecules, and the sequestration of cytokines and chemokines by novel decoy receptors. Our approach to investigate these systems is based on the production of large quantities of soluble protein in heterologous expression systems, allowing for cognate ligand/ receptor discovery, biophysical interaction analyses, high-resolution structure determinations, and targeted functional studies. Together, these approaches provide a wealth of information on the basic tools with which the immune system operates.

Selected Publications:

Edeling MA, Diamond MS, Fremont DH (2014). Structural basis of Flavivirus NS1 assembly and antibody recognition. Proc Natl Acad Sci U S A. 111(11):4285-90. PMID:24594604

Lubman OY, Cella M, Wang X, Monte K, Lenschow DJ, Huang YH, Fremont DH (2014). Rodent herpesvirus Peru encodes a secreted chemokine decoy receptor. J Virol. 88(1):538-46. PMID:24173234

Edeling MA, Austin SK, Shrestha B, Dowd KA, Mukherjee S, Nelson CA, Johnson S, Mabila MN, Christian EA, Rucker J, Pierson TC, Diamond MS, Fremont DH (2014). Potent dengue virus neutralization by a therapeutic antibody with low monovalent affinity requires bivalent engagement. PLoS Pathog. 10(4):e1004072. PMID:24743696.

Luca VC, Nelson CA, and Fremont DH (2013). Structure of the St. Louis encephalitis virus postfusion envelope trimer. Journal of virology, 87(2): 818-28. PMID:23115296

Lazear E, Peterson LW, Nelson CA, and Fremont DH (2013). Crystal Structure of the Cowpox Virus-Encoded NKG2D Ligand OMCP. Journal of virology, 87(2): 840-50. PMID:23115291

McCoy WH 4th, Wang X, Yokoyama WM, Hansen TH, and Fremont DH (2012). Structural Mechanism of ER Retrieval of MHC Class I by Cowpox. PLoS biology, 10(11): e1001432. PMID:23209377

Nelson CA, Warren JT, Wang MW, Teitelbaum SL, and Fremont DH (2012). RANKL employs distinct binding modes to engage RANK and the osteoprotegerin decoy receptor. Structure, 20(11): 1971-82. PMID:23039992

Epperson ML, Lee CA, and Fremont DH (2012). Subversion of cytokine networks by virally encoded decoy receptors. Immunological reviews, 250(1): 199-215. PMID:23046131

Austin SK, Dowd KA, Shrestha B, Nelson CA, Edeling MA, Johnson S, Pierson TC, Diamond MS, and Fremont DH (2012). Structural basis of differential neutralization of DENV-1 genotypes by an antibody that recognizes a cryptic epitope. PLoS pathogens, 8(10): e1002930. PMID:23055922

Luca VC, AbiMansour J, Nelson CA, Fremont DH (2012). Crystal structure of the
Japanese encephalitis virus envelope protein.
J Virol. 86(4):2337-46. PMID:22156523

Last Updated: 4/22/2014 9:28:48 AM

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