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Daniel  A.  Engel
Degree(s): Ph.D.
Graduate School: Yale University
Primary Appointment: Associate Professor of Microbiology
Research Interests:
Drug discovery and molecular biology of influenza; Adenovirus transcriptional regulation.

Email Address: dae2s@virginia.edu
Biomedical Sciences Graduate Program(s)
  • Microbiology, Immunology and Infectious Diseases
  • Biochemistry, Molecular Biology and Genetics
  • Molecular Medicine
    • Research Description

    Molecular Biology of Influenza and Adenovirus. Influenza is a continuing worldwide public health problem. The World Health Organization estimates that there are 250,000 – 500,000 deaths from influenza each year, including 35,000 deaths and 200,000 hospitalizations in the US. The seasonal influenza vaccine and existing anti-viral drugs such as Tamiflu are only partially effective in preventing and combating the disease. In addition, since severe influenza pandemics occurred in 1918, 1957, and 1968, it is anticipated that another pandemic may arise soon, possibly due to the emergence of “avian influenza” H5N1 in the human population. Clearly additional weapons to combat influenza are needed, including new anti-viral pharmaceuticals.

    We have investigated a new influenza drug target, the NS1 protein. NS1 is produced during infection and functions to block the host response to infection. In the absence of NS1, cells produce interferon, which inhibits viral replication through a set of specific cellular pathways. Therefore, in theory, chemical inhibitors of NS1 should restore the host interferon defense system, leading to blockade of virus replication. We have identified several inhibitors of NS1 and these inhibitors in fact block viral replication in cell culture. We are continuing to investigate the effects of the inhibitors on virus replication both in cell culture and in animal models. It is hoped that these studies will lead to effective drugs to treat influenza.

    Adenovirus is a DNA tumor virus that can be used to study mammalian transcriptional regulation and oncogenesis. It has been used extensively to reveal important secrets of cellular function due to its heavy reliance on cellular processes for the purpose of virus replication. For instance, the adenovirus E1A protein inhibits the activity of a key cellular regulator, the retinoblastoma protein, so as to stimulate the infected cell to enter the DNA synthesis phase. Consequently, the mobilized cellular DNA synthesis enzymes serve to enhance replication of the viral DNA as well.

    We are interested in the structure and regulation of adenovirus chromatin, which is controlled by a viral protein called protein VII. We are investigating the role of protein VII in the early transcriptional events of virus replication, and how the functions of protein VII intersect with important cellular functions.

    Selected Publications
  • Basu, D., Walkiewicz, M., Matthew Frieman, Ralph S. Baric, Auble, D.T. and Engel, D.A. 2009. Novel influenza NS1 antagonists block replication and restore innate immune function. J. Virol. 2009 83: 1881-1891.
  • Walkiewicz, M. Morral, N. and Engel, DA. 2009. Accurate single-day titration of adenovirus vectors based on equivalence of protein VII nuclear dots and infectious particles. Submitted.
  • Rao M, Casimiro MC, Lisanti MP, D'Amico M, Wang C, Shirley LA, Leader JE, Liu M, Stallcup M, Engel DA, Murphy DJ, Pestell RG. 2008. Inhibition of cyclin D1 gene transcription by Brg-1. Cell Cycle 7, 647-55.
  • Chen J, Morral N, Engel DA. 2007. Transcription releases protein VII from adenovirus chromatin. Virology. 2007 369, 411-22.
  • PubMed Listings for this Faculty Member
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    Contact Information
      Office Address: PO Box 800734, Jordan Hall, 7224, 
      Office Phone: +1 434-924-8633, +1 434-924-2817
      Fax Phone: +1 434-982-1071
      Home Phone: +1 434-295-9287

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