Summary

Structural virology has fascinated Dr. Norman R. Watts ever since he first discovered the field over 30 years ago. He has studied bacteriophages, crop pathogens and human viruses. In his spare time he enjoys stone carving and high altitude mountaineering.

Research Statement

Dr. Watts’ research is focused on two viruses that have great impacts on people’s health, human immunodeficiency virus (HIV-1) and hepatitis B virus (HBV). Globally, 78 million people have been afflicted with HIV since the beginning of the epidemic, 37 million are living with HIV, and over 1 million die annually of related illnesses. HIV-1 expresses a regulatory protein called Rev that is indispensable for viral replication, yet its complete molecular structure remains unknown and there are no therapeutics that target Rev. The Protein Expression Laboratory, in collaboration with the Laboratory of Structural Biology Research, was the first to solve the atomic structure of the amino-terminal domain of Rev. We are currently pursuing the structure of the carboxyl-terminal domain, and also the structures of Rev in complex with viral RNA and with host proteins. In addition, we have generated synthetic antibody fragments targeted against Rev that strongly inhibit HIV replication in peripheral blood mononuclear cells.

Hepatitis B virus (HBV) is a major cause of liver disease in humans, afflicting almost 400 million worldwide, and is the leading cause of hepatic cancer. HBV expresses a protein indispensable to its replication called “core-antigen” (this forms the virus capsid) and a very closely related protein called “e-antigen” whereby the virus blinds the human immune system to its presence. The Protein Expression Laboratory, again in close collaboration with the Laboratory of Structural Biology Research, has closely examined, primarily by electron microscopy, the interaction of core-antigen with not only numerous monoclonal antibodies widely employed in clinical diagnosis but also the entire antibody repertoire in a patient. In addition, our laboratory was the first to determine the molecular structure of the e-antigen, and the remarkable way in which it differs from core-antigen. With this information we have developed not only the first and only completely molecularly defined clinical assay for HBV, but are also developing specific inhibitors of core-antigen and e-antigen function.

Scientific Publications

A single endoplasmic reticulum aminopeptidase-1 protein allotype is a strong risk factor for Behçet's disease in HLA-B*51 carriers.

Takeuchi M, Ombrello MJ, Kirino Y, Erer B, Tugal-Tutkun I, Seyahi E, Özyazgan Y, Watts NR, Gül A, Kastner DL, Remmers EF
Annals of the rheumatic diseases.
2016 Dec;
75(12).
doi: 10.1136/annrheumdis-2015-209059
PMID: 27217550

The Structure of HIV-1 Rev Filaments Suggests a Bilateral Model for Rev-RRE Assembly.

DiMattia MA, Watts NR, Cheng N, Huang R, Heymann JB, Grimes JM, Wingfield PT, Stuart DI, Steven AC
Structure (London, England : 1993).
2016 Jul 6;
24(7).
doi: 10.1016/j.str.2016.04.015
PMID: 27265851

A cell-penetrating antibody fragment against HIV-1 Rev has high antiviral activity: characterization of the paratope.

Zhuang X, Stahl SJ, Watts NR, DiMattia MA, Steven AC, Wingfield PT
The Journal of biological chemistry.
2014 Jul 18;
289(29).
doi: 10.1074/jbc.M114.581090
PMID: 24878961

Assessment of differences in the conformational flexibility of hepatitis B virus core-antigen and e-antigen by hydrogen deuterium exchange-mass spectrometry.

Bereszczak JZ, Watts NR, Wingfield PT, Steven AC, Heck AJ
Protein science : a publication of the Protein Society.
2014 Jul;
23(7).
doi: 10.1002/pro.2470
PMID: 24715628

An unusual topological structure of the HIV-1 Rev response element.

Fang X, Wang J, O'Carroll IP, Mitchell M, Zuo X, Wang Y, Yu P, Liu Y, Rausch JW, Dyba MA, Kjems J, Schwieters CD, Seifert S, Winans RE, Watts NR, Stahl SJ, Wingfield PT, Byrd RA, Le Grice SF, Rein A, Wang YX
Cell.
2013 Oct 24;
155(3).
doi: 10.1016/j.cell.2013.10.008
PMID: 24243017

Epitope-distal effects accompany the binding of two distinct antibodies to hepatitis B virus capsids.

Bereszczak JZ, Rose RJ, van Duijn E, Watts NR, Wingfield PT, Steven AC, Heck AJ
Journal of the American Chemical Society.
2013 May 1;
135(17).
doi: 10.1021/ja402023x
PMID: 23597076

Antigenic switching of hepatitis B virus by alternative dimerization of the capsid protein.

DiMattia MA, Watts NR, Stahl SJ, Grimes JM, Steven AC, Stuart DI, Wingfield PT
Structure (London, England : 1993).
2013 Jan 8;
21(1).
doi: 10.1016/j.str.2012.10.017
PMID: 23219881

Specificity of an anti-capsid antibody associated with Hepatitis B Virus-related acute liver failure.

Wu W, Chen Z, Cheng N, Watts NR, Stahl SJ, Farci P, Purcell RH, Wingfield PT, Steven AC
Journal of structural biology.
2013 Jan;
181(1).
doi: 10.1016/j.jsb.2012.10.004
PMID: 23079477

Education

Agriculture Canada
NSERC Postdoctoral Fellow, 1992–1994

University of Minnesota
NSERC Postdoctoral Fellow, 1990–1992

University of New Brunswick, Canada
Ph.D., 1990

Experience

Staff Scientist
Protein Expression Laboratory, NIAMS/NIH, 1999–present

Fogarty Fellow
Laboratory of Structural Biology Research, NIAMS/NIH, 1994–1999

Last Updated: July 2020