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Summary
Paul T. Wingfield, Ph.D. received his doctoral degree from Dundee University, Scotland, in 1975 following his work on the composition and structure of components of the inner membrane of beef heart mitochondria under the supervision of Prof. Peter B. Garland. From 1975 to 1977 he did postdoctoral training with Profs. Alex N. Glazer & Robert J. Delange at the University of California, Los Angeles. Following a position as Staff Scientist in the Biological Structures Division at the European Molecular Biology Laboratory, Heidelberg, Germany (1977 to 1981), Dr. Wingfield served as Department Head of Protein Chemistry, first at Biogen (1981 to 1987) and then at the Glaxo Institute for Molecular Biology (1987 to 1989) in Geneva, Switzerland. He then became Manager of the Department of Molecular Genetics & Protein Chemistry at Pfizer Central Research, Groton, Connecticut (1991 to 1992). Since then, he has served as Laboratory Chief of the Protein Expression Laboratory at the NIAMS and as Acting Laboratory Chief of the Laboratory of Structural Biology Research (NIAMS).
Research Statement
The Protein Expression Laboratory (PEL) was established in 1990 in the Office of the Director by the Deputy Director for Intramural Research with the mission to produce and characterize human immunodeficiency virus (HIV-1) proteins for the intramural research effort. Extensive collaborations with NIH investigators have led to numerous publications and significant advances. In 1996, the PEL was transferred to the NIAMS, leading to an extended and highly productive collaboration with the Laboratory of Structural Biology Research (LSBR/NIAMS) headed by Dr. Alasdair Steven, a world leader in the field of cryo-electron microscopy.
Individuals with HIV-1 are frequently co-infected with hepatitis B virus (HBV) due to similar routes of transmission. Chronic viral hepatitis in recent years has become one of the most frequent causes of hospital admissions and mortality among HIV-infected patients. In this way, chronic HBV behaves as an opportunistic infection in the context of HIV infection. The management of HIV-positive individuals should include prevention, regular screening for HBV infection, and the administration of anti-HBV therapy to co-infected patients. The long-term efficacy and safety of combination treatment with agents that exert activity against both viruses also warrant investigation.
Together, the PEL and LSBR have made numerous important advances in the understanding of both HIV-1 and HBV.
Key accomplishments
- First structure determination of HIV-1 Rev.
- First structure determination of HIV-1 RRE.
- First structure determination of HIV-1 Nef.
- First structure determination of HIV-1 Protease in solution.
- First structure determination of SIV gp41 ectodomain.
- Structure and dynamics of HIV-1 Reverse transcriptase RNAase H domain .
- Structure and dynamics of interleukin-1 and interleukin-4.
- Engineering a chimeric human/rabbit Fab with anti-HIV activity.
- Confirmation of the fullerene conjecture in retroviral capsid assembly.
- HIV maturation inhibitor Bevirimat stabilizes the immature Gag lattice.
- Discovery of the role of HIV-1 integrase in virion assembly.
- First structure determination of the HBV capsid.
- HBV e antigen assay with exceedingly high sensitivity and specificity.