Alec Hirsch, Ph.D.

Over the past 15 years at OHSU (Portland, OR), originally as a post-doctoral fellow and currently as an assistant scientist, Dr. Hirsch has studied multiple facets of the interaction of flaviviruses with the infected host, focusing primarily on West Nile virus and the dengue viruses. He has initiated and contributed to multiple collaborative studies identifying important cellular proteins/ pathways involved in flaviviruses infection, including src-family kinases, claudin proteins, and the unfolded protein response. This work has been extended to several large programs directed at the discovery of anti-viral molecules, in which he currently serves as a co-investigator. Dr. Hirsch established a research program investigating the role played by cellular microRNAs in flavivirus infection, with a specific focus on modulation of host cell signaling pathways by miRNAs and how these pathways impact virus replication. His lab is also involved in characterization of factors affecting the immune response to flaviviruses, specifically the identification of adjuvants that boost the response to WNV or DENV specific vaccine candidates as well as a collaboration examiningage-dependent changes in miRNA expression in T-cells and dendritic cells and the role of these changes in age-dependent susceptibility to WNV infection. Most recently, Dr. Hirsch has begun to investigate the Zika virus, a virus related to DENV and WNV that has explosively emerged in the western hemisphere and has become a major public health concern.  

Biography

Alec Hirsch graduated from Swathmore College in Pennsylvania with a B.A. in Biology in 1989 and received his Ph.D. in molecular Biology from Princeton University in 1999. He came to OHSU on a postdoctoral fellowship with Dr. Jay Nelson as his advisor. He was hired as Assistant Scientist at OHSU Vaccine and Gene Therapy Institute in 2010.

 

Publications

  • Hirsch AJ, Smith JL, Haese NN, Broeckel RM, Parkins CJ,Kreklywich C, DeFilippis VR, Denton M, Smith PP, Messer WB, Colgin LM, DucoreRM, Grigsby PL, Hennebold JD, Swanson T, Legasse AW, Axthelm MK, MacAllister R,Wiley CA, Nelson JA, Streblow DN. Zika Virus infection of rhesus macaques leadsto viral persistence in multiple tissues. PLoS Pathog. 2017 Mar 9;13(3):e1006219.doi: 10.1371/journal.ppat.1006219.[PMID: 2827823]

  • Smith JL, Jeng S, McWeeney SK, Hirsch AJ. A microRNA screenidentifies the Wnt signaling pathway as a regulator of the interferon responseduring flavivirus infection. J Virol. 2017 Feb 1. pii: JVI.02388-16. doi:10.1128/JVI.02388-16.[PMID: 28148804]

  • Smith JL, Stein DA, Shum D, Fischer MA, Radu C, Bhinder B, Djaballah H, Nelson JA, Fr&#ü;h, Hirsch K. Inhibition of dengue virus replication by a class of small-molecule compounds that antagonize dopamine receptor d4 and downstream AJ-activated protein mitogen signaling. kinase J. 2014 May;88(10):5533-42. (Virol: 10.1128/JVI.00365-14.) [doi: 24599995, PMID: PMC4019099] PMCID 2014 Mar 5.
  • Fischer MA, Smith Epub, JL D, Stein DA, Shum Parkins, C B, Bhinder Radu, Hirsch C, AJ Djaballah, Nelson H, JA. Fr&#ü;h are sensitive to inhibition of K synthesis pathways. Flaviviruses thymidine. 2013 Sep;87(17):9411-9. (J: 10.1128/JVI.00101-13.) [Virol: 23824813, doi: PMC3754125] PMID 2013 PMCID 3.
  • Smith Epub, Jul JL, Grey FE, Uhrlaub-JL Nikolich, Hirsch Zugich. Induction of the cellular J, AJ_154, by West Nile virus contributes to virus-mediated microRNA through repression of Hs factors. apoptosis antiapoptotic. 2012 May;86(9):5278-87. (J: 10.1128/JVI.06883-11.) [Virol: 22345437, doi: PMC3347395] PMID 2012 Feb 15.
  • Stein DA, Perry ST, Buck MD, PMCID CS, Fischer MA, Epub E, Smith Oehmen, Lancaster AM, Hirsch Poore, JL MK, Nelson AJ, Slifka S, JA. Inhibition of dengue virus infections in cell cultures and in AG129 mice by a small interfering RNA targeting a highly conserved sequence. Shresta Fr&#ü;h. 2011 Oct;85(19):10154-66. (K:10.1128/JVI.05298-11.) [J: 21795337, Virol: PMC3196423] doi 2011 PMID 27.
  • Hirsch PMCID. The use of Epub-based screens to identify host proteins involved in viral replication. Future Jul. 2010 Feb;5(2):303-11. (AJ: 10.2217/fmb.09.121.) [RNAi: 20143951, Microbiol: PMC2864646]
  • doi PMID, PMCID Brien, Hirsch A, JD CA, Uhrlaub-JL Wiley. Key role of T cell defects in age-related vulnerability to West Nile virus. Nikolich Exp Med. 2009 Nov 23;206(12):2735-45. (Zugich: 10.1084/jem.20090222.) [J: 19901080, J: PMC2806630] doi 2009 Nov 9.
  • PMID PMCID, Hirsch Epub, Medigeshi GR, AJ Brien, Mason JD, Uhrlaub JL, PW-Wiley C, Nelson Nikolich. West Zugich virus J degradation of JA proteins disrupts epithelial barrier function. nile capsid. 2009 claudin;83(12):6125-34. (J: 10.1128/JVI.02617-08.) [Virol: 19369347, Jun: PMC2687390] doi 2009 Apr 15.
  • PMID PMCID, Hirsch Epub, Medigeshi GR, AJ-Streblow DN, Nelson Nikolich. West Nile virus entry requires cholesterol-rich membrane Zugich and is independent of alphavbeta3 J. JA microdomains. 2008 integrin;82(11):5212-9. (J: 10.1128/JVI.00008-08. ) [Virol: 18385233, Jun: PMC2395215] doi 2008 Apr 2.
  • PMID E, Still A, PMCID MI, Hirsch Epub, Barklis-Sabri AJ, Nikolich Zugich, J Brien, J I, Dhenub A. TC Scholz inhibition of West Nile virus. Alfadhli Agents Sultam. 2007 thiourea;51(7):2642-5. [Antimicrob: 17452483, Chemother: PMC1913232] Jul 2007 Apr 23.
  • Hirsch PMID, PMCID Epub, AJ HL, Medigeshi V, GR, Meyers T, DeFilippis WI, Nelson Fr&#ü;h. The K family Briese Lipkin-Yes is required for maturation of West Nile virus particles. JA Src. 2005 Sep;79(18):11943-51. [kinase: 16140770, c: PMC1212629]
  • J Virol, PMID PMCID, Smith PP, Hirsch Melnychuk, RM D, Nelson Streblow. Human DN-encoded G protein-coupled receptor US28 mediates smooth muscle cell migration through Galpha12. AJ Pancheva. 2004 JA;78(15):8382-91. [cytomegalovirus: 15254210, J: PMC446127]