Assistant Professor of Microbiology and Immunology
Assistant Professor of Biochemistry and Molecular Biology
Department of Pathology, Microbiology, and Immunology
Basic Medical Sciences Building, Lab Rm. 314; Office Rm. 313
New York Medical College
Valhalla, NY 10595
Undergraduate degree: B.S. in Biochemistry, Clemson University, Clemson, South Carolina
Graduate degree: M.S. in Chemistry, University of Wisconsin–Milwaukee, Milwaukee, Wisconsin
Ph.D.: Biochemistry, North Carolina State University, Raleigh, North Carolina
Postdoctoral Training: University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
Epstein-Barr Virus (EBV) is a DNA human herpesvirus which causes infectious mononucleosis and B-cell lymphomas in immunocompromised individuals. EBV is also closely associated with Hodgkin’s lymphoma, Burkitt’s lymphoma, and nasopharyngeal carcinoma. There is currently no efficacious treatment for EBV, and the need for improved therapies is driven by people immunosuppressed due to AIDS, organ transplantation, cancer and aging. Approximately 90-95% of the world’s population is infected with EBV, and most infections occur in childhood and are typically asymptomatic.
My laboratory’s work spans the virology of a human tumor virus and ubiquitin systems as regulators of viral and cellular protein function. Current work focuses on viral and cellular interactions and resulting downstream functional consequences of the EBV late lytic gene BPLF1. BPLF1 is a deubiquitinating enzyme (DUB) with its enzymatic activity encoded in the first 205 amino acids. Protein ubiquitination plays indispensable roles in many cellular and viral processes. Monoubiquitination modifications usually result in regulation of functional activity of protein targets, whereas polyubiquitination may suggest that the tagged protein will be targeted for degradation depending on the type of ubiquitin linkage.
Our work has implicated BPLF1 in a wide range of viral and cellular processes including infectivity, viral DNA replication, and DNA repair. Also we demonstrated that knockout of BPLF1 delays and reduces human B-cell immortalization and lymphoma formation in humanized mice. These findings attest to BPLF1’s importance in understanding the roles of herpesviral deubiquitinating activity in both lytic and persistent infections. Inhibition of EBV’s DUB activity provides a new approach to specific therapy of EBV infections.
Current research plans include 1) examining effects of BPLF1 on DNA repair processes, 2) examining the global effects of a BPLF1 knockout virus in vitro and in vivo with a humanized mouse model, 3) identifying and characterizing viral and cellular targets of BPLF1 deubiquitinating activity, and 4) screening compound libraries to identify inhibitors of BPLF1.
Small Molecule Screening Identifies Inhibitors of Epstein-Barr Virus Deubiquitinating Enzyme, BPLF1. Sage L. Atkins, Safiyyah Motaib, Laura C. Wiser, Sharon E. Hopcraft, Paul B. Hardy, Peter Foote, Ashley H. Wade Blossom A. Damania, Joseph S. Pagano, Kenneth H. Pearce, and Christopher B. Whitehurst. Antiviral Res. 2020 Jan;173:104649. doi: 10.1016/j.antiviral. 2019.104649. PMID:31711927.
Antiviral Drugs for EBV. Joseph S.Pagano, Christopher B. Whitehurst, Graciella Andrei. Cancers (Basel). 2018 Jun 13;10(6). pii: E197. doi: 10.3390/cancers10060197. PubMed PMID: 29899236.
Translesion Polymerase, pol ƞ, is Required for Efficient Epstein-Barr Virus Infectivity and is Regulated by the Viral Deubiquitinating Enzyme, BPLF1. Ossie F. Dyson, Joseph S. Pagano, and Christopher B. Whitehurst. J Virol. 2017 Sep 12;91(19). PMID:28724765.
Knockout of EBV’s BPLF1 Reduces B-cell Transformation and Tumor Formation in Humanized Mice. Christopher B. Whitehurst, Guangming Li, Stephanie A. Montgomery, Nathan D. Montgomery, Lishan Su, and Joseph S. Pagano. mBio 2015. Oct;6(5):e01574-15. doi:10.1128/mBio.01574-15. PMID: 26489865.
The Rad6/18 Ubiquitin Complex Interacts with the Epstein-Barr Virus Deubiquitinating Enzyme, BPLF1, and Contributes to Virus Infectivity. Christopher B. Whitehurst, Ravindra Kumar*, and Joseph S. Pagano. J Virol. 2014 Jun;88(11):6411-22. PMID: 24672041.
Maribavir Inhibits Epstein-Barr Virus Transcription Through the EBV Protein Kinase. Christopher B. Whitehurst, Marcia K. Sanders, Mankit Law, Fu-Zhang Wang, Jie Xiong, Dirk P. Dittmer, and Joseph S. Pagano. J Virol. 2013 May;87(9):5311-5. PMID:23449792
The Epstein-Barr Virus BPLF1 protein deubiquitinates PCNA and attenuates Polƞ recruitment to sites of DNA damage. Christopher B. Whitehurst, Cyrus Vaziri, Julia Shackelford, and Joseph S. Pagano. J Virol. 2012 Aug;86(15):8097-106. PMID: 22623772
Maribavir Inhibits Epstein-Barr Virus Transcription in Addition to Viral DNA Replication. Fu-Zhang Wang, Debasmita Roy, Edward Gershburg, Christopher B. Whitehurst, Dirk P.Dittmer, and Joseph S, Pagano. J Virol. 2009 Dec;83(23):12108-17. PMID:19759127
The EBV Deubiquitinating Enzyme, BPLF1, Reduces EBV Ribonucleotide Reductase Activity. Christopher B. Whitehurst, Shunbin Ning, Gretchen L. Bentz, Florent Dufour, Edward Gershburg, Julia Shackelford, Yves Langelier, and Joseph S. Pagano. J Virol. 2009 May;83(9):4345-53. PMID:19244336