Fatah Kashanchi Ph.D., Director of Research, NCBID, School of Systems Biology


Dr. Kashanchi received his Ph.D. in 1990 in Microbiology with emphasis on HIV gene expression. He then moved to Washington, Dc for his post doctoral and Research Associate fellowship at National cancer Institute, National Institutes of Health from 1991-1998.   He was Tenured at the George Washington University medical school as a full Professor in 2004. He moved to GMU as director of research in 2010.

Research Interests


Human retroviruses, biodefense viral agents, Cell cycle, host-pathogen interactions, small molecule and peptide inhibitors against transcription machinery, RNAi machinery and its components, proteomics and metabolomics, and  humanized mouse models.

Research Program


The current research in the Kashanchi Lab is focused on defining transcriptional and chromatin mediated regulation of HIV and HTLV-1 infected cells.  Our studies have resulted in novel concepts regarding promoter-bound proteins that regulate all events of mRNA biogenesis (including capping, elongation, termination, poly A addition, splicing), nuclear-cytoplasmic transport, and activation of nonsense mRNA degradation. Among biothreat agents, the Kashanchi lab is interested in Rift Valley fever virus (RVFV) and Venuzueln Equine Encepalitis virus (VEEV) replication in vitro and in vivo and defining crucial host-pathogen interactions that are imperative to pathogenesis.

Transcription and Chromatin: Number of chromatin remodeling complexes belonging to SWI/SNF have been studied in relation to both HIV-1 and HTLV-1 transcription. One specific complex called PBAF is responsible for activation of both viral promoters in the presence of the activators Tat and Tax. Furthermore, one specific component namely Baf170 is highly regulated and expressed in retrovirally infected cells. Nucleosome positioning of promoter elements specifically at +1 region indicates changes in histone content and post-translational modifications on both promoters.  These changes are regulated by PBAF complex and acetylated viral proteins.

RNAi Machinery: Work in my lab has shown that critical differences exist in the microRNA machinery in T-cells versus monocyte/macrophages. Monocytes do not have a central protein call DICER and differentiated macrophages have low levels of DICER protein. Furthermore, the presence of complete RNAi machinery in T-cells contributes to presence of viral miRNA, which in turn controls latency and suppresses viral gene expression through epigenetic means. An example of such viral miRNA is shown in a stem and loop structure called TAR which is present at high levels in infected cells (105 copies). The effect of the miRNA is on both on viral and cellular genes, which contribute to anti-apoptotic nature of this miRNA.

Inhibitors of transcription and other related pathways: My lab has published and focused on a number of CDK inhibitors, as well as, other host signaling pathways including GSK. The ATP analogs that constitute the majority of the CDK inhibitors are easy to make and fairly selective in HIV infected cells. The reason for the selectivity is the nature of the kinases altered after infection and the substrates that they phosphorylate which are dramatically different.  Furthermore, many of the drug inhibitors enhance the level of short transcripts (TAR), which contribute to further specificity on HIV-1 and cellular promoters.

RVFV and VEEV. The research focuses on the use of Reverse phase Protein MicroArray (RPMA) and other phosphoproteomic methods to decipher signal transduction modulation following viral infection that contribute to infection and replication of these two viruses in multiple host cells. Efforts are underway to define relevant biomarkers both in infected and uninfected cells using standard mass spectrometry approaches and novel metabolomics approaches (Laser Ablation Electrospray Ionization Mass Spectrometry developed by colleagues at the George Washington University), and identify inhibitors of host activated pathways that contribute to pathogenesis.

Humanized mouse models: the lab utilizes a number of humanized animal models, including Rag double knockout, as well as, NOD/SCID animals to study HIV-1 and HTLV-1 infections. Various organs from infected animals are used to define viral tropism and evaluate how small molecule and peptide inhibitors effectively contribute to inhibition of virus replication in these humanized animals.

Relevant Publications (selected from 135 PubMed citations)

Narayanan, A., et al., Exosomes derived from HIV-1 infected cells contain TAR RNA. J Biol Chem, 2013.

Klase, Z.A., G.C. Sampey, and F. Kashanchi, Retrovirus infected cells contain viral microRNAs. Retrovirology, 2013. 10: p. 15.

Sampey, G.C., et al., Complex role of microRNAs in HTLV-1 infections. Front Genet, 2012. 3: p. 295.

Van Duyne, R., et al., Effect of mimetic CDK9 inhibitors on HIV-1-activated transcription. J Mol Biol, 2013. 425(4): p. 812-29.

Chung, M.C., et al., Bacillus anthracis-derived nitric oxide induces protein S-nitrosylation contributing to macrophage death. Biochem Biophys Res Commun, 2013. 430(1): p. 125-30.

Tonry, J.H., et al., In vivo murine and in vitro M-like cell models of gastrointestinal anthrax. Microbes Infect, 2013. 15(1): p. 37-44.

Narayanan, A., et al., Curcumin inhibits Rift Valley fever virus replication in human cells. J Biol Chem, 2012. 287(40): p. 33198-214.

Van Duyne, R., et al., Localization and sub-cellular shuttling of HTLV-1 tax with the miRNA machinery. PLoS One, 2012. 7(7): p. e40662.

Narayanan, A., et al., Use of ATP analogs to inhibit HIV-1 transcription. Virology, 2012. 432(1): p. 219-31.

Austin, D., et al., p53 Activation following Rift Valley fever virus infection contributes to cell death and viral production. PLoS One, 2012. 7(5): p. e36327.

Kehn-Hall, K., et al., Modulation of GSK-3beta activity in Venezuelan equine encephalitis virus infection. PLoS One, 2012. 7(4): p. e34761.

Al-Harthi, L. and F. Kashanchi, Mechanisms of HIV-1 latency post HAART treatment area. Curr HIV Res, 2011. 9(8): p. 552-3.

Tyagi, M. and F. Kashanchi, New and novel intrinsic host repressive factors against HIV-1: PAF1 complex, HERC5 and others. Retrovirology, 2012. 9: p. 19

Duyne, R.V., et al., Humanized mouse models of HIV-1 latency. Curr HIV Res, 2011. 9(8): p. 595-605.

Van Duyne, R., et al., Varying modulation of HIV-1 LTR activity by Baf complexes. J Mol Biol, 2011. 411(3): p. 581-96.

Kehn-Hall, K., et al., Inhibition of Tat-mediated HIV-1 replication and neurotoxicity by novel GSK3-beta inhibitors. Virology, 2011. 415(1): p. 56-68.

Carpio, L., et al., microRNA machinery is an integral component of drug-induced transcription inhibition in HIV-1 infection. J RNAi Gene Silencing, 2010. 6(1): p. 386-400.

Van Duyne R, Guendel I, Narayanan A, Gregg E, Shafagati N, Tyagi M, Easley R, Klase Z, Nekhai S, Kehn-Hall K, Kashanchi F. Varying Modulation of HIV-1 LTR Activity by BAF Complexes. J Mol Biol. 2011 Aug 19;411(3):581-96.

Kehn-Hall K, Guendel I, Carpio L, Skaltsounis L, Meijer L, Al-Harthi L, Steiner JP, Nath A, Kutsch O, Kashanchi F. Inhibition of Tat-mediated HIV-1 replication and neurotoxicity by novel GSK3-beta inhibitors. Virology. 2011 Jun 20;415(1):56-68.

Carpio L, Klase Z, Coley W, Guendel I, Choi S, Van Duyne R, Narayanan A, Kehn-Hall K, Meijer L, Kashanchi F.  microRNA machinery is an integral component of drug-induced transcription inhibition in HIV-1 infection. J RNAi Gene Silencing. 2010;6(1):386-400. PMCID: 20628499.

Coley W, Van Duyne R, Carpio L, Guendel I, Kehn-Hall K, Chevalier S, Narayanan A, Luu T, Lee N, Klase Z, Kashanchi F. Absence of DICER in monocytes and its regulation by HIV-1. J Biol Chem. 2010 Oct 15;285(42):31930-43.

Easley R, Carpio L, Dannenberg L, Choi S, Alani D, Van Duyne R, Guendel I, Klase Z, Agbottah E, Kehn-Hall K, Kashanchi F.  Transcription through the HIV-1 nucleosomes:  Effects of the PBAF complex in Tat activated transcription.  Virology. 2010;405(2):322-333.  PMCID: 20599239.

Kashanchi F, Kehn-Hall K Novel insights into transcriptional elongation: ubiquitination of HEXIM1 and p-TEFb activity. Cell Cycle. 2009 Aug 15;8(16):2485. PMCID: PMC Journal – In Process

Zhou M, Huang K, Jung KJ, Cho WK, Klase Z, Kashanchi F, Pise-Masison CA, Brady JN. Bromodomain protein Brd4 regulates human immunodeficiency virus transcription through phosphorylation of CDK9 at threonine 29. J Virol. 2009 Jan;83(2):1036-44. PMCID: PMC2612389

Van Duyne R, Easley R, Wu W, Berro R, Pedati C, Klase Z, Kehn-Hall K, Flynn EK, Symer DE, Kashanchi F. Lysine methylation of HIV-1 Tat regulates transcriptional activity of the viral LTR. Retrovirology. 2008 May 22, 5:40.  PMCID: PMC2412914

Berro R, Pedati C, Kehn-Hall K, Wu W, Klase Z, Even Y, Geneviere AM, Ammosova T, Nekhai S, Kashanchi F. CKD13, a new potential human immunodeficiency virus type 1 inhibitory factor regulating viral mRNA splicing. J. Virol. 2008 Jul; 82 (14): 7155-66. PMCID: PMC2446983

Van Duyne R, Cardenas J, Easley R, Wu W, Kehn-Hall K, Klase Z, Mendez S, Zeng C, Chen H, Saifuddin M, Kashanchi F.  Effect of transcription peptide inhibitors on HIV-1 replication.  Virology. 2008 Jul 5; 376(2): 308-22.

Klase Z, Kale P, Winograd R, Gupta MV, Heydarian M, Berro R, McCaffrey T, Kashanchi F. HIV-1 TAR element is processed by Dicer to yield a viral micro-RNA involved in chromatin remodeling of the viral LTR. BMC Mol Biol. 2007 Jul 30;8(1):63