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MMI Faculty

Debby Burshtyn, PhD

DebbyBurshtyn
Dept. of Medical Microbiology & Immunology
University of Alberta
Faculty of Medicine & Dentistry
6-59A Heritage Medical Research Centre
T6G 2S2 Edmonton, AB
Canada
Ph : (780) 492-0646
Fx : (780) 492-7521
Em: burshtyn@ualberta.ca

 

Positions:

  • Associate Professor, Dept. of Medical Microbiology & Immunology
  • AHFMR Senior Scholar
  • Graduate Coordinator

 

Research:

Background:  Cytotoxic T cells and natural killer cells are motile cells that enter an infected tissue from the blood and are able to recognize and destroy cells infected with a virus while sparing the surrounding tissue.  Natural killer cells use a combination of activating and inhibitory receptors to determine if a cell should be lysed.  The activating receptors bind to markers of cellular stress and occasionally viral proteins.  Killer cell Ig-like receptors (KIRs) bind to MHC molecules expressed on all normal healthy cells.  The MHC are often targeted for removal from the cell surface by viruses or lost during tumor progression to evade T cells.  The cells without MHC are more susceptible to natural killer cell-mediated lysis due to loss of the inhibitory signal. There are more than 10 distinct KIR genes within the KIR family and each one exhibits extensive polymorphism in the human population.  Various KIR genotypes have been associated with increased resistance to chronic hepatitis C and HIV progression.

How KIR work: Killer cells destroy target cells by polarized degranulation of lytic granules at the point of contact. Degranulation is initiated by tyrosine phosphorylation events emanating from activating receptors following their binding to ligands on the target cell. However, if KIRs are also engaged at the point of contact with the target cell, they are phosphorylated and subsequently recruit and activate the tyrosine phosphatase SHP-1. SHP-1 then blocks the activation pathway by dephosphorylating various molecules involved in the activation signaling cascade.

Current projects:  We are investigating the mechanism of collaboration between various KIRs and a related receptor LIR1 that we believe broadens the specificity of many KIR alleles. The expression pattern LIR1 on natural killer cells varies widely from person to person and we are currently investigating the basis of this diversity with a view to determining implications for susceptibility and resistance to infectious diseases, autoimmunity and cancer.  We are also engaged in studies of how KIR relocate in order to target activated SHP-1 to its substrates, and NK receptor regulation of adhesion to target cells. To study these questions we are using a combination of molecular, biochemical and live cell-imaging approaches.

 

NK cell inhibiting & activating receptors

Figure 1 abbreviations: KIR, killer cell inhibitory receptor; MHC-1, class I major histocompatibility molecule; PTK, protein tyrosine kinase; pY, phosphotyrosine.

If you are interested in postdoctoral studies please submit a CV including contact information for 3 references and a brief description of how your background and education fit with our laboratory interests.

If you are interested in graduate studies please send by email a brief description of your background research experience, future career goals and a copy of your transcripts.  

Further information regarding the MMI graduate program can be found through the MMI Homepage.

 

People:

  • Li Fu (Graduate Student)
  • Nicholas Li (Graduate Student)
  • Chelsea Davidson (Graduate Student)
  • Kinola Williams (Graduate Student)

 

Publications:

Click here for most recent publications

 

Selected Publications:

  1. Poxvirus Infection-Associated Downregulation of C-Type Lectin-Related-b Prevents NK Cell Inhibition by NK Receptor Protein-1B. Williams KJ, Wilson E, Davidson CL, Aguilar OA, Fu L, Carlyle JR, and DN Burshtyn. 2012 Journal of Immunology 188:4980-91 (CIHR 36344)

  2. Montgomery, B.C, Cortes, H.D., Burshtyn, D.N., and J.L. Stafford. Channel catfish leukocyte immune-type receptor mediated inhibition of cellular cytotoxicity is facilitated by SHP-1-dependent and -independent mechanisms.  2012  Developmental & Comparative Immunology 37:151-163  (CIHR 36344)

  3. Li, N.L., Davidson, C.E., Humar, A. and D.N. Burshtyn.  Modulation of the inhibitory receptor leukocyte Ig-like receptor 1 on human natural killer cells.  Frontiers in NK Cell Biology, available on line Sept 06, 2011. (CIHR 36344)

  4. The first Ig-domain of KIR3DL1 contacts MHC-I at a secondary site.  Fu, L., Hazes B. and D.N. Burshtyn, 2011 Journal of Immunology 187:1816-25  (CIHR 36344)

  5. Davidson, C., Li, N. and D.N. Burshtyn. LILRB1 polymorphism and surface phenotype of natural killer cells.  2010 Human Immunology 71:942.  (CIHR 36344)

  6. Osman, MS, Burshtyn, DN, Kane, KP. Activating Ly-49 receptors regulate LFA-1-mediated adhesion by NK cells. J Immunol 2007 Feb 1;178(3):1261-7

  7. Kirwan,  SE, Burshtyn, DN.  Regulation of natural killer cell activity.
    Curr Opin Immunol. 2007 Feb;19(1):46-54

  8. Treanor, B, Lanigan, PM, Kumar, S, Dunsby, C, Munro, I, Auksorius, E, Culley, FJ, Purbhoo, MA, Phillips, D, Neil, MA, Burshtyn, DN, French, PM, Davis, DM. Microclusters of inhibitory killer immunoglobulin-like receptor signaling at natural killer cell immunological synapses.  J Cell Biol. 2006 Jul 3;174(1):153-61

  9. Kirwan, S, Merriam, D, Barsby, N, McKinnon, A, Burshtyn, DN. Vaccinia virus modulation of natural killer cell function by direct infection. Virology. 2006 Mar 30;347(1):75-87

  10. Kirwan, SE, Burshtyn, DN. Killer cell Ig-like receptor-dependent signaling by Ig-like transcript 2 (ILT2/CD85j/LILRB1/LIR-1).J Immunol. 2005 Oct 15;175(8):5006-15

  11. Standeven, LJ, Carlin, LM, Borszcz, P, Davis, DM, Burshtyn, DN. The actin cytoskeleton controls the efficiency of killer Ig-like receptor accumulation at inhibitoryNK cell immune synapses. J Immunol. 2004 Nov 1;173(9):5617-25

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