Viral pathogenesis and viral evasion strategies from the host immune response
Recombinant vaccinia viruses as vaccine vectors
Counter-bioterrorism research focusing on smallpox
Vaccinia virus, Recombinant vaccines, poxvirus , pathogenesis, smallpox vaccines and therapeutics, molluscum contagiosum
Description of Research
Dr. Isaacs' laboratory focuses on using poxviruses as a model system to study viral proteins that are involved in viral pathogenesis, dissemination, and evasion of the host immune response. Poxviruses, which are used widely as a tool for research and vaccine development, express proteins that inhibit complement activation, bind IL-1, TNF, and interferons, and decrease the host inflammatory response by other mechanisms. Elucidation of these processes could lead to a safer virus vector. Furthermore, the study of these defense molecules encoded by the virus might give insights into the control of inflammation, as well as, the development of new anti-inflammatory drugs. The laboratory has also been pursuing the use of vaccinia virus as a vaccine vector and with anti-bioterrorism research. Dr. Isaacs was the poxvirus program project leader for the Middle Atlantic Regional Center of Excellence in Biodefense and Emerging Infectious Diseases and was involved in developing a safer smallpox vaccines as well as therapies to treat smallpox and complications from the current smallpox vaccine.
The Isaacs lab is also working with molluscum contagiosum, a poxvirus that causes a very common skin infection, especially in children. This virus has been difficult to study because it cannot be grown in cell culture. The Isaacs lab is pursuing approaches to grow this virus in cell culture systems.
Past lab personnel:
General Infectious Diseases
Buchman, G.W., Cohen, M.E., Xiao, Y., Richardson-Harman, N., Silvera, P., DeTolla, L.J., Davis, H.J., Eisenberg, R.J., Cohen, G.H., Isaacs, S.N. : A protein-based smallpox vaccine protects non-human primates from a lethal monkeypox virus challenge. Vaccine 28(40): 6627-36, Sep 2010.
DeHaven, B.C., Girgis, N.M., Xiao, Y., Hudson, P.N., Olson, V.A., Damon, I.K., Isaacs, S.N. : Poxvirus complement control proteins are expressed on the cell surface through an intermolecular disulfide bridge with the viral A56 protein Journal of Virology 84(21): 11245-11254, Nov 2010.
Isaacs, S.N. : A stimulating way to improve T cell responses to poxvirus-vectored vaccines. Journal of Clinical Investigation 121(1): 19-21, Jan 2011 Notes: Invited, peer-reviewed commentary.
Girgis, N.M., DeHaven, B.C., Xiao, Y., Alexander, E., Viner, K.M., Isaacs, S.N.: The vaccinia virus complement control protein modulates adaptive immune responses during infection. Journal of Virology 85(6): 2547-56, Mar 2011 Notes: Selected by Editors of Journal of Virology for "Spotlight Feature", which highlights 5 articles as meritorious.
Cohen ME, Xiao Y, Eisenberg RJ, Cohen GH, Isaacs SN: Antibody against Extracellular Vaccinia Virus (EV) Protects Mice through Complement and Fc Receptors. PLoS ONE 6(6): e20597, Jun 2011.
Hudson, P.N., Self, J., Weiss, S., Braden, Z., Xiao, Y., Girgis, N.M., Emerson, G., Hughes, C., Sammons, S.A., Isaacs, S.N., Damon, I.K., Olson, V.A.: Elucidating the role of the complement control protein in monkeypox pathogenicity.
PLoS One 7(4): e35086, Apr 2012.
Xiao, Y. and Isaacs, S.N.: Enzyme-Linked Immunosorbent Assay (ELISA) and Blocking with Bovine Serum Albumin (BSA) - Not all BSAs are alike. Journal of Immunological Methods 384(1-2): 148-51, Oct 2012.
Isaacs, S.N. (Editor): Vaccinia Virus and Poxvirology: Methods and Protocols, 2nd Edition. in Methods in Molecular Biology. Humana Press : Springer, 890, Jul 2012.
Xiao, Y., Zeng, Y., Alexander, E., Mehta, S., Joshi, S.B., Buchman, G.W., Volkin, D.B., Middaugh, C.R., Isaacs, S.N.: Adsorption of recombinant poxvirus L1-protein to aluminum hydroxide/CpG vaccine adjuvants enhances immune responses and protection of mice from vaccinia virus challenge. Vaccine 31(2): 319-326, Jan 2013.
Guan, H., Nuth, M., Zhukovskaya, N., Saw, Y.L., Bell, E., Isaacs, S.N., Ricciardi, R.P.: A novel target and approach for identifying antivirals against molluscum contagiosum virus. Antimicrobial Agents and Chemotherapy 58(12): 7383-9, Dec 2014 Notes: My lab made and tested the recombinant vaccinia virus that was critical to this publication.
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Last updated: 03/23/2016
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