B.S., 1981, Biochemistry, Pennsylvania State University
Ph.D., 1988, Microbiology and Immunology, University of North Carolina at Chapel Hill
Postdoctoral research: University of North Carolina at Chapel Hill and University of California, San Francisco
Hepatitis B viruses (HBV) are a family of DNA viruses that can persistently infect the liver of a variety of animal hosts including humans. There is a close association between chronic HBV infection and hepatocellular carcinoma, though the mechanism of oncogenesis is not understood. Although they have a DNA genome, hepadnaviruses replicate via reverse transcription of an RNA intermediate (RNA pregenome) resulting in a relaxed circular DNA genome. The major project in our laboratory is understanding the mechanism of HBV reverse transcription. We are studying the mechanisms of RNA encapsidation, initiation and synthesis of minus-strand DNA, initiation and synthesis of plus-strand DNA, and genome circularization during plus-strand DNA synthesis. To understand the mechanism of these processes during reverse transcription we are (1) defining the cis-acting sequences involved in each step of the process, (2) determining the role of the viral trans-acting factors in each step of the process, and (3) determining the nature of the interactions between the trans-acting factors and the cis-acting elements during the process of reverse transcription.
Unchwaniwala N, Sherer NM, Loeb DD. Hepatitis B Virus Polymerase Localizes to the Mitochondria, and Its Terminal Protein Domain Contains the Mitochondrial Targeting Signal. J Virol. 2016 Sep 12;90(19):8705-19. doi: 10.1128/JVI.01229-16. Print 2016 Oct 1. PubMed PMID: 27440888; PubMed Central PMCID: PMC5021430.
Tan Z, Pionek K, Unchwaniwala N, Maguire ML, Loeb DD, Zlotnick A. The interface between hepatitis B virus capsid proteins affects self-assembly, pregenomic RNA packaging, and reverse transcription. J Virol. 2015 Mar;89(6):3275-84. doi: 10.1128/JVI.03545-14. Epub 2015 Jan 7. PubMed PMID: 25568211; PubMed Central PMCID: PMC4337549.
Greco, N., Hayes, M. H., and Loeb, D. D. Snow Goose Hepatitis B Virus (SGHBV) Envelope and Capsid Proteins Independently Contribute to the Ability of SGHBV to Package Capsids Containing Single-Stranded DNA in Virions. J. Virol., 88(18): 10705-10713, 2014.
Wang, J. C.-Y., Nickens, D. G., Lentz, T. B., Loeb, D. D., and Zlotnick, A. Encapsidated Hepatitis B Virus Reverse Transcriptase Is Poised on an Ordered RNA Lattice. Proc. Natl. Acad. Sci. USA, 111(31): 11329-11334, 2014.
Tan, Z., Maguire, M. L., Loeb, D. D., and Zlotnick, A. Genetically Altering the Thermodynamics and Kinetics of Hepatitis B Virus Capsid Assembly Has Profound Effects on Virus Replication in Cell Culture. J. Virol., 87(6): 3208-3216, 2013.
Member, American Cancer Society Study Section, Microbial Pathogenesis and Cancer Peer Review Committee, 2007-present