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Research > Faculty By Division > Daved Fremont, PhD

Associate Professor, Pathology and Immunology
Associate Professor, Biochemistry and Molecular Biophysics
Room 7701, CSRB
Office: (314) 747-6547
Lab: (314) 747-4546
E-mail: fremont@wustl.edu
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Research

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 are 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.

Service to the University

1999 - PresentLecturer in Foundations in Immunology, Protein Structure and Function, Protein Crystallography, and Molecular Cell Biology
1998 - PresentMember, Molecular Biophysics Graduate Program Steering Committee

DBBS Graduate Program Affiliation

Member, Division of Biology and Biomedical Sciences Admissions Committee

Selected Publications

Ota N, Brett TJ, Murphy TL, Fremont DH, Murphy KM.. N-domain dependent Stat-4 dimerization required for cytokine-driven activation.. Nat Immunol 2:208-215, 2004 Abstract

Iizuka K, Naidenko OV, Plougastel BF, Fremont DH, Yokoyama WM.. Genetically linked C-type lectin-related ligands for the NKRP1 family of natural killer cell receptors.. Nat Immunol 4:801-807, 2003 Abstract

Lybarger L, Yu YY, Miley MJ, Fremont DH, Myers N, Primeau T, Truscott SM, Connolly JM, Hansen TH.. Enhanced immune presentation of a single-chain class I molecule engineered to optimize linkage of a C-terminal extended peptide.. J Biol Chem 278:27105-27111, 2003 Abstract

Miley MJ, Truscott SM, Yu YY, Gilfillan S, Fremont DH, Hansen TH, Lybarger L.. Biochemical features of the MHC-related protein 1 consistent with an immunological function.. J Immunol 170:6090-6098, 2003 Abstract

Backström E, Chambers BJ, Ho EL, Naidenko OV, Mariotti R, Fremont DH, Yokoyama WM, Kristensson K, Lj. Natural killer cell-mediates lysis of dorsal root ganglia neurons via RAE1/NKG2D interactions.. Eur J Immunol 33:92-100, 2003 Abstract

Alexander JM, Nelson CA, van Berkel V, Lau EK, Studts JM, Brett TJ, Speck SH, Handel TM, Virgin HW,. Structural basis of chemokine sequestration by a herpesvirus decoy receptor.. Cell 111:343-356, 2002 Abstract

Carayannopoulos LN, Naidenko OV, Fremont DH, Yokoyama WM.. Cutting edge: Murine UL16-binding protein-like transcript 1: a newly described transcript encoding a high-affinity ligand for murine NKG2D.. J Immunol 169:4079-4083, 2002 Abstract

Smith HR, Heusel JW, Mehta IK, Kim S, Dorner BG, Naidenko OV, Iizuka K, Furukawa H, Beckman DL, Ping. Recognition of a virus-encoded ligand by a natural killer cell activation receptor.. Proc Natl Acad Sci USA 99:8826-8831, 2002 Abstract

Brett TJ, Traub LM, Fremont DH.. Accessory protein recruitment motifs in clathrin-mediated endocytosis.. Structure 10:797-809, 2002 Abstract

Fremont DH, Dai S, Chiang H, Crawford F, Marrack P, Kappler J.. Structural basis of cytochrome c presentation by I-Ek. J Exp Med 195:1043-1052, 2002 Abstract

Facchetti F, Cella M, Festa S, Fremont DH, Colonna M.. An unusual Fc receptor-related protein expressed in human centroblasts.. Proc Natl Acad Sci USA 99:3776-3781, 2002 Abstract

Arentson E, Faloon P, Seo J, Moon E, Studts JM, Fremont DH, Choi K.. Oncogenic potential of the DNA replication licensing protein CDT1.. Oncogene 21:1150-1158, 2002 Abstract

Carayannopoulos LN, Naidenko OV, Kinder J, Ho EL, Fremont DH, Yokoyama WM.. Ligands for murine NKG2D display heterogeneous binding behavior.. Eur J Immunol 32:597-605, 2002 Abstract

Lam J, Nelson CA, Ross FP, Teitelbaum SL, Fremont DH.. Crystal structure of the TRANCE/RANKL cytokine reveals determinants of receptor-ligand specificity.. J Clin Invest 108:971-979, 2001 Abstract

Messaoudi I, LeMaoult J, Metzner BM, Miley MJ, Fremont DH, Nikolich-Zugich J.. Functional evidence that conserved TCR CDR 3 áloop docking governs the cross-recognition of closely related peptide:class I complexes. J Immunol 167:836-843, 2001 Abstract

Wilson N, Fremont D, Marrack P, Kappler J.. Mutations changing the kinetics of class II MHC peptide exchange.. Immunity 14:513-522, 2001 Abstract

Kersh GJ, Miley MJ, Nelson CA, Grakoui A, Horvath S, Donermeyer DL, Kappler J, Allen PM, Fremont DH.. Structural and functional consequences of altering a peptide MHC anchor residue.. J Immunol 166:3345-3354, 2001 Abstract

Latek RR, Suri A, Petzold S, Nelson CA, Kanagawa O, Unanue ER, Fremont DH.. Structural basis of peptide binding and presentation by the type I diabetes-associated MHC class II molecule of NOD mice.. Immunity 12:699-710, 2000 Abstract

Traub LM, Downs MA, Westrich JL, Fremont DH.. Crystal structure of the alpha appendage of AP-2 reveals a recruitment platform for clathrin-coat assembly.. Proc Natl Acad Sci USA 96:8907-8912, 1999 Abstract

Nelson CA, Fremont DH.. Structural principles of MHC class II antigen presentation. Rev Immunogenet. 1:47-59, 1999 Abstract


Current Trainees

Jennifer Alexander
Chung Lee
Bill McCoy
Grant Nybakken
Phoebe Arnold
Vesselin Mitaksov, PhD
Olga Naidenko
Bruce Thompson Jr.
Thomas Brett

Past Trainees

Wen-Hung (Michael) Wang, MD