Welcome to the Barr Lab

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Dr. Stephen Barr, PhD
Associate Professor
Dept. of Microbiology & Immunology
Western University
Schulich School of Medicine & Dentistry, Center for Human Immunology
London, Ontario N6A 5C1
Phone: 519-661-3438
Fax: 519-661-3499
Email: Stephen Barr" <stephen.barr@uwo.ca>


Restriction Factors

Interferon has been shown to inhibit acute and chronic HIV replication, but little is known about the effector mechanisms of the host interferon response to HIV infection and whether HIV can circumvent these mechanisms. We have previously identified two interferon-induced proteins called TRIM22 and HERC5 that are produced in high abundance during the interferon response and are capable of potently inhibiting various steps of the HIV life cycle. Our research will provide a deeper understanding of the human innate immune response towards HIV, which will in turn lead to novel approaches for antiviral therapeutics and personalized medicine for HIV-infected individuals.

HIV Integration

During infection, the genome of human immunodeficiency virus (HIV) permanently incorporates itself into the cellular genome in a process called integration. This event leads to life-long infection and is typically accompanied by a dormant period (e.g. several years) where HIV expression is barely detectable (i.e. HIV latency). Eliminating this dormant pool of HIV remains a major obstacle in curing HIV infection. We recently discovered a new feature in our genome called non-B DNA that attracts integration of the HIV genome and potentially contributes to the establishment and maintenance of HIV-1 latency, thereby having direct bearing on cure-focused research. Our research investigates the mechanisms of how HIV targets non-B DNA for integration and how non-B DNA contributes to HIV latency. Our research will help inform the design of experiments in HIV eradication research and in designing better gene therapy vectors that are based on HIV biology (e.g. lentivectors).


Recent Publications:

  1. McAllister RG, Liu J, Woods MW, Tom SK, Rupar CA, and Barr SD. (2014) Lentivector integration sites in ependymal cells from a model of metachromatic leukodystrophy: non-B DNA as a new factor influencing integration. Molecular Therapy Nucleic Acids (Aug 26; 3:e187).
  2. Jenna N. Kelly and Stephen D. Barr. (2014) In silico analysis of functional single nucleotide polymorphisms in the human TRIM22 gene. PLoS One Jul 1; 9(7):e101436.
  3. Jenna N. Kelly, Matthew W. Woods, Sintia Xhiku and Stephen D. Barr. (2014) Ancient and recent adaptive evolution in the antiviral TRIM22 gene: identification of a single nucleotide polymorphism that profoundly impacts TRIM22 function. Human Mutation. DOI: 10.1002/humu.22595
  4. Woods, M.W., Tong, J.G., Tom, S., Szabo, P.A., Haeryfar, S.M.M., Cavanagh, P.C., Dikeakos, J.D. and Barr**, S.D. (2014) Interferon-induced HERC5 is evolving under positive selection and inhibits HIV-1 particle production by a novel E3 ligase-independent mechanism targeting Rev/RRE-dependent RNA nuclear export. Retrovirology 11:27 Highly Accessed.
  5. Woods, M.W. and Barr, S.D.** (2014) Human HERC5 is a novel E3 ligase that restricts an early stage of HIV-1 assembly. Advances in Virus Research.  iConcept Press. ISBN: 978-14775550-4-0.
  6. Hattlmann, C.J., Kelly, J.N., and Barr, S.D.** TRIM22: a highly diverse and dynamic antiviral protein. (2012). Molecular Biology International.Volume 2012, Article ID 153415
  7. Miller, M.S., Pelka, P., Foseca, G.J., Cohen, M.J., Kelly, J.N., Barr, S.D., Grand, R.J.A., Turnell, A.S., Whyte, P., and Mymryk, J.S. (2012) Characterization of the 55 residue protein encoded by the 9S E1A mRNA of species c adenovirus. Journal of Virology In Press.
  8. Ha, S., Park, S., Hattlmann, C.J.,  Barr, S.D., and Kim, S. (2011) Inhibition or deficiency of cathepsin B leads defects in HIV-1 Gag pseudoparticle release in macrophages and HEK293T cells. Antiviral Research 93(1):175-84.
  9. Woods, M.W., Kelly, J.N., Hattlmann, C.J., Tong, J.G.K., Xu, L.S., Coleman, M.D., Quest, G.R., Smiley, J.R., Barr, S.D**. (2011). Human HERC5 restricts an early stage of HIV-1 assembly by a mechanism correlating with the ISGylation of Gag. Retrovirology 8:95. Highly Accessed.
  10. Kelly, J., Tong, J., Hattlmann, C., Woods, M., Barr**, S.D. (2011) Book Title: HIV and AIDS– Updates on Biology, Immunology, Epidemiology and Treatment Strategies. Chapter Title: “Cellular Restriction Factors: Can We Exploit the Body’s Natural Antiviral Proteins to Combat HIV/AIDS?” Open Access ISBN 978-953-307-665-2.
  11. Barr**, S.D. (2010). Cellular HIV-1 restriction factors: a new avenue for AIDS therapy? Future Virology 5(4):417-433.  
  12. Ciuffi, A. and Barr**, S.D. (2010). Identifying HIV integration sites in the human genome. Methods 53(1):39-46.
  13. Barr**, S.D, Smiley, J.R. and Bushman, F.D. (2008). The Interferon Response Inhibits HIV Particle Production By Induction Of TRIM22. PLoS Pathogens.  4(2): e1000007.
  14. Barr, S.D., Ciuffi, A., Leipzig, J., Shinn, P., Ecker, J.R. and Bushman**, F.D. (2006). HIV integration site selection: Targeting in macrophages and the effects of different routes of viral entry. Molecular Therapy 14(2):218-225. 
  15. Bushman** F, Lewinski M, Ciuffi A, Barr S, Leipzig J, Hannenhalli S, Hoffmann C. (2005). Genome-wide analysis of retroviral DNA integration. Nature Reviews Microbiology 3(11):848-58.
  16. Barr, S.D., Leipzig, J., Shinn, P., Ecker, J.R. and Bushman**, F.D. (2005). Integration targeting by avian sarcoma-leukosis virus and human immunodeficiency virus in the chicken genome. Journal of Virology 79(18):12035-44.
  17. Bogner, E.  and  A. Holzenburg (eds). New concepts of antiviral Therapies. Springer, New York, Dodrecht.  (2006).  ISBN 0-387-31046-0; Authors: Reeves, J.D., Barr, S. and Pohlmann**, S. Chapter title- HIV Inhibition: Integrase Inhibitors.