Isaac Jensen, PhD

Graduate Student, Interdisciplinary Graduate Program in Immunology 2016-2020
Postdoctoral Research Fellow 2020-2021
Biography

Education

Bachelor of Science in Biology - University of North Dakota
PhD - University of Iowa 2020

Research

NK cell responses control and define the sepsis-induced cytokine storm and immunoparalysis state

Sepsis is a dysregulated host response to systemic infection that leads to immunologic dysfunction and organ damage. This dysregulated host response, termed the cytokine storm, is composed of both pro- and anti-inflammatory cytokines that are detrimental or beneficial to host survival, respectively. While early intervention has improved survival of the acute inflammatory event, approximately 20% of people still succumb to the cytokine storm. Frustratingly, >100 phase II and II clinical trials aimed at limiting pro-inflammatory cytokines have failed indicating a greater need to understand the cytokine storm in order to improve patient outcomes. Yet, even as survival of the septic event has increased, it has become apparent that septic patients experience a prolonged state of immunologic dysfunction, termed immunoparalysis, that reduces host capacity to respond to secondary infections. My thesis work focuses on NK cells to understand the interplay between cellular responses and the septic event, this is with respect to both how NK cells influence septic inflammation and how NK cells become impaired contributing to the immunoparalysis state.

Publications

  1. Berton RR, PW McGonagill, IJ Jensen, TK Ybarra, GA Bishop, JT Harty, TS Griffith, and VP Badovinac. Sepsis leads to lasting changes in phenotype and function of naïve CD8 T cells. PLoS Pathog 10: e1011720 (2023) [PubMed]
  2. Heidarian M, IJ Jensen, SK Kannan, LL Pewe, M Hassert, S Park, HH Xue, JT Harty*, and VP Badovinac*.  Sublethal whole-body irradiation induces permanent loss and dysfunction in pathogen-specific circulating memory CD8 T cell populations.  PNAS 120: e2302785120 (2023) [PubMed]
  3. Moioffer SJ, RR Berton, PW McGonagill, IJ Jensen, TS Griffith, and VP Badovinac. Inefficient recovery of repeatedly stimulated memory CD8 T cells after polymicrobial sepsis induction leads to changes in memory CD8 T cell pool composition. J Immunol 210: 168-179 (2023) [PubMed]
  4. Jensen IJ, MD Martin, SK Tripathy, and VP Badovinac. Novel mouse model of MCMV-induced adaptive NK cells. Immunohorizons 6: 8-15 (2022)[PubMed]
  5. Berton RR, IJ Jensen, JT Harty, TS Griffith, and VP Badovinac. Inflammation controls susceptibility of immune experienced mice to sepsis. Immunohorizons 6: 825-842 (2022)[PubMed]
  6. Lefebvre MN, FA Surette, SM Anthony, R Vijay, IJ Jensen, LL Pewe, LS Hancox, N Van Braeckel-Budimir, S Van de Wall, SL Urban, MR Mix, SP Kurup, VP Badovinac, NS Butler, and JT Harty. Expeditious recruitment of circulating memory CD8 T cells to the liver facilitates control of malaria. Cell Rep 37: 109956 (2021)
  7. Jensen IJ, L Xiang, PW McGonagill, Q Shan, MG Fosdick, MM Tremblay, JCD Houtman, HH Xue, TS Griffith, W Peng, and VP Badovinac*. Sepsis leads to lasting changes in phenotype and function of memory CD8 T cells. eLife 10: e70989 (2021) [PubMed]
  8. Jensen IJ*, SN Jensen*, PW McGonagill, TS Griffith, AK Mangalam*, and VP Badovinac*. Autoimmunity increases susceptibility to and mortality from sepsis. Immunohorizons 5: 844-854 (2021)
  9. Miljkovic D, S Stanisavljevic, IJ Jensen, TS Griffith, and VP Badovinac. Sepsis and multiple sclerosis: causative links and outcomes. Immunol Lett 238: 40-46 (2021) [PubMed]
  10. Moioffer SJ*, DB Danahy*, S van de Wall, IJ Jensen, FV Sjaastad, SM Anthony,  JT Harty, TS Griffith, and VP Badovinac. Severity of sepsis determines the degree of impairment observed in circulatory and tissue-resident memory CD8 T cell populations. J Immunol 207: 1871-1881 (2021) [PubMed]
  11. Jensen IJ, PW McGonagill, RR Berton, BA Wagner, EE Silva, GR Buettner, TS Griffith, and VP Badovinac. Prolonged ROS production following septic insult. Immunohorizons 5: 477-488 (2021)  [PubMed]
  12. Antony SM*, N Van Braeckel-Budimir*, SJ Moioffer, S van de Wall, Q Shan, R Vijay, R Sompallae, SM Hartwig, IJ Jensen, SM Varga, NS Butler, HH Xue, VP Badovinac*, and JT Harty*. Protective function and durability of mouse lymph node resident memory CD8 T cells. eLife 10: e68662 2021) [PubMed]
  13. Jensen IJ, PW McGonagill, NS Butler, JT Harty, TS Griffith, and VP Badovinac.  NK cell-derived IL-10 supports host survival during sepsis. J Immunol 206: 1171-1180 (2021) [PubMed]
  14. Brate AA, AW Boyden, IJ Jensen, VP Badovinac, and NJ Karandikar.  A functionally distinct CXCR3+/IFNg+/IL-10+ subsets definesdisease-suppresive CNS-specific CD8 T cells. J Immunol 206: 1151-1160 (2021) [PubMed]
  15. Jensen IJ, SN Jensen, FV Sjaastad, KN Gibson-Corley, T Dileepan, TS Griffith, AK Mangalam, and VP Badovinac. Sepsis impedes EAE disease development and diminishes autoantigen-specific CD4 T cells. eLife 9: e55800 (2020) [PubMed]
  16. Sjaastad FV, IJ Jensen,RR Berton, VP Badovinac, and TS Griffith.  Inducing experimental polymicrobial sepsis by cecal ligation and puncture.  Curr Protoc Immunol 131: e110 (2020) [PubMed]
  17. Urban SL, IJ Jensen, Q Shan, LL Pewe, HH Xue, VP Badovinac, and JT Harty.  Peripherally induced brain tissue-resident memory CD8 T cells mediate protection against CNS infection.  Nat Immunol 8: 938-949 (2020) [PubMed]
  18. Jensen IJ, PW McGonagill, MN Lefebvre, TS Griffith, JT Harty, and VP Badovinac.  Worry and FRET: ROS production leads to fluorochrome tandem degradation annd impairs interpretation of flow cytometric results.  Immunity 52: 419-421 (2020) [PubMed]
  19. Espinosa-Cotton M, EJ Fertig, LP Stabile, AG Davis, JE Bauman, S Schmitz, KN Gibson-Corley, Y Cheng, IJ Jensen, VP Badovinac, D Laux, and AL Simons. A preliminary analysis of interleukin-1 ligands as potential predictive biomarkers of response to cetuximab.  Biomark Res 7: 14 (2019) [PubMed]
  20. Huggins MA, FV Sjaastad, M Pierson, TA Kucaba, W Swanson, C Staley, AR Weingarden, IJ Jensen, DB Danahy, VP Badovinac, SC Jameson, V Vezys, D Masopust, A Khortus, TS Griffith, and SE Hamilton. Microbial exposure enhances immunity to pathogens recognized by TLR2 but increases susceptibility to cytokine storm via TLR4 sensitization. Cell Rep 28: 1729-1743 (2019) [PubMed]
  21. Danahy DB,  IJ Jensen,  TS Griffith, VP Badovinac. Cutting Edge: Polymicrobial Sepsis Has the Capacity to Reinvigorate Tumor-Infiltrating CD8 T Cells and Prolong Host Survival. J Immunol 202: 2843 (2019) [PubMed]
  22. Espinosa-Cotton M, SN Rodman Iii S, KA Ross, IJ Jensen, K Sangodeyi-Miller, AJ McLaren, RA Dahl, KN Gibson-Corley KN, AT Koch, YX Fu, VP Badovinac, D Laux, B Narasimhan, AL Simons . Interleukin-1 alpha increases anti-tumor efficacy of cetuximab in head and neck squamous cell carcinoma. J Immunother Cancer 7:79 doi: 10.1186/s40425-019-0550-z. (2019) [PubMed]
  23. Danahy DB, SP Kurup, CS Winborn, IJ Jensen, JT Harty, TS Griffith, VP Badovinac. Sepsis-Induced State of Immunoparalysis Is Defined by Diminished CD8 T Cell-Mediated Antitumor Immunity. J Immunol 203: 725-735 (2019) [PubMed]
  24. Martin MD, IJ Jensen, AS Ishizuka, M Lefebvre, Q Shan, HH Xue, JT Harty, RA Seder, VP Badovinac. Bystander responses impact accurate detection of murine and human antigen-specific CD8 T cells. J Clin Invest 130: 3894-3908 (2019) [PubMed]
  25. Jensen IJ, CS Winborn, MG Fosdick, P Shao, MM Tremblay, Q Shan, SK Tripathy, CM Snyder, HH Xue, TS Griffith, JC Houtman, VP Badovinac. Polymicrobial sepsis influences NK-cell-mediated immunity by diminishing NK-cell-intrinsic receptor-mediated effector responses to viral ligands or infections. PLoS Pathog 14:10 (2018) [PubMed]
  26. Jensen IJ, FV Sjaastad, TS Griffith, VP Badovinac. Sepsis-Induced T Cell Immunoparalysis: The Ins and Outs of Impaired T Cell Immunity. J Immunol 200: 1543-1553. (2018) [PubMed]
  27. Danahy DB, SM Anthony, IJ Jensen, SM Hartwig, Q Shan, HH Xue, JT Harty, TS Griffith, and VP Badovinac. Polymicrobial sepsis impairs bystander recruitment of effector cells to infected skin despite optimal sensing and alarming function of skin resident memory CD8 T cells. PLoS Pathog 13: 9 (2017) [PubMed]
Isaac Jensen