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Current Students

Martinov
Tijana Martinov

Email:mart3527@umn.edu

Thesis Advisor: Brian Fife

Year entered: 2013

Degrees received:
B.A., Macalester College, St. Paul, MN, 2012

Honors and Awards:

  • Best Poster (Graduate student category) at the Robert Hebbel Department of Medicine Research Day (May 2014)
  • MICaB student service award (April 2016)
  • Golden Pipetman Award, Fall 2016
  • AAI Young Investigator Award, Autumn Immunology Conference, Fall 2016
  • Frieda Matha Kunze Fellowship, 2017-2018
  • Theodore Milne and Beatrice Brandenberg Award, Spring 2017
  • J. Jacob Kaplan Award, Spring 2017
  • Steer Family Award in Diabetes Research, Spring 2017
  • Association for Multicultural Scientists, President, 2016-17, 2017-18
  • Empowering Women in Science, Co-founder and Progress Chair
  • MICaB Career Development Committee Member, 2015-present

 

Research:
Type 1 Diabetes (T1D) is a CD4 T cell-driven autoimmune condition that results in
destruction of the pancreatic islets of Langerhans, and consequent loss of insulin
production. Insulin itself is one of the main targets in human T1D patients and in non-obese
diabetic (NOD) mice. With this in mind, our lab has developed insulin-peptide/MHC Class II
tetramer reagents that allow us to track islet-reactive CD4 T cells prior to and during
disease progression in NOD mice. Using these reagents, we have been able to identify and
phenotype insulin-specific CD4 T cells, and show that they expand as NOD mice approach
disease onset. Having the reagents to track autoreactive cells also allowed us to investigate
how they are regulated. Programmed death-1 (PD-1) is a T cell inhibitory receptor, and
deficiency or blockade of this receptor or its ligand (PD-L1) accelerates disease onset in
NOD mice. We demonstrated that the majority of insulin-specific CD4 T cells express PD-1,
and that the level of PD-1 expression is proportional to the cell’s affinity for self-antigen. In
other words, PD-1 preferentially restrained those cells with the highest autoimmune threat.
Blocking PD-1/PD-L1 pathway unleashed the accumulation of high-affinity insulin-specific
CD4 T cells in the pancreas. This work helps explain how some patients treated with PD-1
blockade for advanced malignancies develop autoimmunity, including type 1 diabetes. By
understanding how various subsets of islet-reactive lymphocytes respond to PD-1 blockade,
we hope to better predict patients’ responses to this treatment modality and decrease sideeffects
from cancer immunotherapy.

Publications:

  • Spanier JA, Sahli NL, Wilson JC, Martinov T, Dileepan T, Burrack AL, Finger EB, Blazar BR, Michels AW, Moran A, Jenkins MK, Fife BT. 2017. Increased Effector Memory Insulin-Specific CD4(+)T-cells Correlate with Insulin Autoantibodies in Recent-Onset Type 1 Diabetic Patients. Diabetes. 2017, pii: db170666. PMID: 28842400.
  • Schuldt NJ, Auger JL, Spanier JA, Martinov T, Breed ER, Fife BT, Hogquist KA, Binstadt BA. 2017. Cutting Edge: Dual TCRα Expression Poses an Autoimmune Hazard by Limiting Regulatory T Cell Generation. J Immunol. 199(1):33-38.
  • Landry J, Martinov T, Mengistu H, Dhanwada J, Benck CJ, Kline J, Boo B, Swanson L, Tonc E, Daughters R, Fife BT, Chatterjea D. Repeated hapten exposure induces persistent tactile sensitivity in mice modeling localized provoked vulvodynia. PLoS One. 2017, 12(2):e0169672.
  • Jiang TT*, Martinov T*, Xin L, Kinder JM, Spanier JA, Fife BT, Way SS. Programmed Death-1 Culls Peripheral Accumulation of High-Affinity Autoreactive CD4 T Cells to Protect against Autoimmunity. Cell Rep. 2016, 17(7):1783-1794. *denotes equal contributions.
  • Martinov T, Spanier JA, Pauken KE, Fife BT. PD-1 pathway-mediated regulation of islet specific CD4(+) T cell subsets in autoimmune diabetes. Immunoendocrinology. 2016; 3. pii: e1164.
  • Spanier J.A., D.R. Frederick, J.J. Taylor, J.R. Heffernan, D. Kotov, T. Martinov, K.C. Osum, J.L. Ruggiero, B.J. Rust, S.J. Landry, M.K. Jenkins, J.B. McLachlan, B.T. Fife. 2016. Efficient generation of monoclonal antibodies against peptide in the context of MHCII using magnetic enrichment. Nat Commun. 7:11804.
  • Martinov T., B.T. Fife. 2016. Commentary: Fractionated radiotherapy combined with PD-1 pathway blockade promotes CD8 T cell-mediated tumor clearance for the treatment of advanced malignancies. Ann Transl Med. 4:82.
  • Benck C.J., T. Martinov, B.T. Fife, D. Chatterjea. 2016. Isolation of infiltrating leukocytes from mouse skin using enzymatic digest and gradient separation. J Vis Exp. 107:e53638.
  • Martinov T., J.A. Spanier, K.E. Pauken, B.T. Fife. 2016. PD-1 pathway-mediated regulation of islet-specific CD4+ T cell subsets. Immunoendocrinology. 3:e1164.
  • Pauken, K.E.*, Nelson C.E.*, Martinov T.*, J. A. Spanier, J.R. Heffernan, N.L. Sahli, C. F. Quarnstrom, K.C. Osum, J.M. Schenkel, M.K. Jenkins, B.R. Blazar, V. Vezys and B.T. Fife. 2015. Cutting Edge: Identification of autoreactive CD4+ and CD8+ T cell subsets resistant to PD-1 pathway blockade. Journal of Immunology 194(8):3551-5.
    *authors contributed equally