David James Pickup, PhD

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Associate Professor of Virology in the Department of Molecular Genetics and Microbiology
Department:
Molecular Genetics and Microbiology
Address:
421 Jones Bldg
Durham, NC 27710
Office Telephone:
(919) 684-2480
Training:
  • PhD, National Institute For Medical Research, London, 1979
Research Interests:


The primary focus of our group is upon the mechanisms by which orthopoxviruses affect host functions, particularly those involved in host immune processes. We are employing poxviruses in these studies, because these viruses, which encode over 200 proteins, are unusually adept and sophisticated in targeting components of the immune system. Recently, we have primarily investigated the ways in which poxviruses modify cytokine-mediated responses to infection. We have shown that these viruses affect these responses in several different ways: (i) by preventing the synthesis of cytokines; (ii) by encoding soluble secreted versions of receptors for cytokines; and (iii) by interfering with cytokine signaling pathways. Currently, we are particularly interested in how poxviruses (in a species-specific way) positively or negatively affect the activation of NF-kappaB transcription factors. Knowledge of the fundamental mechanisms involved in poxviral interference with host processes should assist the development of therapies and vaccines for a variety of conditions associated with infectious diseases, inflammatory diseases, autoimmune diseases, cancers, and transplantation.

A second focus of our group is the development improved vaccines against variola and related orthopoxviruses. As part of the South Eastern Regional Center of Excellence in Emerging Infections and Biodefense, we are collaborating with investigators at both the University of North Carolina at Chapel Hill (Dr. B. Johnston), and Emory University (Dr. M. Feinberg), to develop better virus-based vaccines against variola virus. In addition, together with Dr. Barbara Sherry (College of Veterinary Medicine, North Carolina State University) we are investigating the effects of vaccinia virus-based vaccines upon cardiac cells and the heart. In these two projects, our goals are to develop potent vaccines that pose far fewer risks of complications than those currently available.
Representative Publications:
  • Byun, M; Verweij, MC; Pickup, DJ; Wiertz, EJ; Hansen, TH; Yokoyama, WM. Two mechanistically distinct immune evasion proteins of cowpox virus combine to avoid antiviral CD8 T cells. Cell Host and Microbe. 2009;6:422-432.  Abstract
  • Lynch, HE; Ray, CA; Oie, KL; Pollara, JJ; Petty, IT; Sadler, AJ; Williams, BR; Pickup, DJ. Modified vaccinia virus Ankara can activate NF-kappaB transcription factors through a double-stranded RNA-activated protein kinase (PKR)-dependent pathway during the early phase of virus replication. Virology. 2009;391:177-186.  Abstract
  • Pickup, DJ. Understanding orthopoxvirus interference with host immune responses to inform novel vaccine design. Expert Review of Vaccines. 2007;6:87-95.  Abstract
  • Thornburg, NJ; Ray, CA; Collier, ML; Liao, HX; Pickup, DJ; Johnston, RE. Vaccination with Venezuelan equine encephalitis replicons encoding cowpox virus structural proteins protects mice from intranasal cowpox virus challenge. Virology. 2007;362:441-452.  Abstract
  • D'Costa, SM; Antczak, JB; Pickup, DJ; Condit, RC. Post-transcription cleavage generates the 3' end of F17R transcripts in vaccinia virus. Virology. 2004;319:1-11.  Abstract
  • McKelvey, TA; Andrews, SC; Miller, SE; Ray, CA; Pickup, DJ. Identification of the orthopoxvirus p4c gene, which encodes a structural protein that directs intracellular mature virus particles into A-type inclusions. Journal of Virology. 2002;76:11216-11225.  Abstract
  • Panus, JF; Smith, CA; Ray, CA; Smith, TD; Patel, DD; Pickup, DJ. Cowpox virus encodes a fifth member of the tumor necrosis factor receptor family: a soluble, secreted CD30 homologue. Proceedings of the National Academy of Sciences of USA. 2002;99:8348-8353.  Abstract
  • Oie, KL; Pickup, DJ. Cowpox virus and other members of the orthopoxvirus genus interfere with the regulation of NF-kappaB activation. Virology. 2001;288:175-187.  Abstract
  • Howard, ST; Ray, CA; Patel, DD; Antczak, JB; Pickup, DJ. A 43-nucleotide RNA cis-acting element governs the site-specific formation of the 3' end of a poxvirus late mRNA. Virology. 1999;255:190-204.  Abstract
  • Loparev, VN; Parsons, JM; Knight, JC; Panus, JF; Ray, CA; Buller, RM; Pickup, DJ; Esposito, JJ. A third distinct tumor necrosis factor receptor of orthopoxviruses. Proceedings of the National Academy of Sciences of USA. 1998;95:3786-3791.  Abstract
  • Smith, CA; Smith, TD; Smolak, PJ; Friend, D; Hagen, H; Gerhart, M; Park, L; Pickup, DJ; Torrance, D; Mohler, K; Schooley, K; Goodwin, RG. Poxvirus genomes encode a secreted, soluble protein that preferentially inhibits beta chemokine activity yet lacks sequence homology to known chemokine receptors. Virology. 1997;236:316-327.  Abstract
  • Quan, LT; Tewari, M; O'Rourke, K; Dixit, V; Snipas, SJ; Poirier, GG; Ray, C; Pickup, DJ; Salvesen, GS. Proteolytic activation of the cell death protease Yama/CPP32 by granzyme B. Proceedings of the National Academy of Sciences of USA. 1996;93:1972-1976.  Abstract
  • Smith, CA; Hu, FQ; Smith, TD; Richards, CL; Smolak, P; Goodwin, RG; Pickup, DJ. Cowpox virus genome encodes a second soluble homologue of cellular TNF receptors, distinct from CrmB, that binds TNF but not LT alpha. Virology. 1996;223:132-147.  Abstract
  • Hu, FQ; Smith, CA; Pickup, DJ. Cowpox virus contains two copies of an early gene encoding a soluble secreted form of the type II TNF receptor. Virology. 1994;204:343-356.  Abstract
  • Antczak, JB; Patel, DD; Ray, CA; Ink, BS; Pickup, DJ. Site-specific RNA cleavage generates the 3' end of a poxvirus late mRNA. Proceedings of the National Academy of Sciences of USA. 1992;89:12033-12037.  Abstract
  • Ray, CA; Black, RA; Kronheim, SR; Greenstreet, TA; Sleath, PR; Salvesen, GS; Pickup, DJ. Viral inhibition of inflammation: cowpox virus encodes an inhibitor of the interleukin-1 beta converting enzyme. Cell. 1992;69:597-604.  Abstract
  • Spriggs, MK; Hruby, DE; Maliszewski, CR; Pickup, DJ; Sims, JE; Buller, RM; VanSlyke, J. Vaccinia and cowpox viruses encode a novel secreted interleukin-1-binding protein. Cell. 1992;71:145-152.  Abstract
  • Ink, BS; Pickup, DJ. Vaccinia virus directs the synthesis of early mRNAs containing 5' poly(A) sequences. Proceedings of the National Academy of Sciences of USA. 1990;87:1536-1540.  Abstract
  • Patel, DD; Pickup, DJ. Messenger RNAs of a strongly-expressed late gene of cowpox virus contain 5'-terminal poly(A) sequences. The EMBO Journal. 1987;6:3787-3794.  Abstract
  • Pickup, DJ; Ink, BS; Hu, W; Ray, CA; Joklik, WK. Hemorrhage in lesions caused by cowpox virus is induced by a viral protein that is related to plasma protein inhibitors of serine proteases. Proceedings of the National Academy of Sciences of USA. 1986;83:7698-7702.  Abstract
  • Pickup, DJ; Ink, BS; Parsons, BL; Hu, W; Joklik, WK. Spontaneous deletions and duplications of sequences in the genome of cowpox virus. Proceedings of the National Academy of Sciences of USA. 1984;81:6817-6821.  Abstract
  • Pickup, DJ; Bastia, D; Stone, HO; Joklik, WK. Sequence of terminal regions of cowpox virus DNA: arrangement of repeated and unique sequence elements. Proceedings of the National Academy of Sciences of USA. 1982;79:7112-7116.  Abstract