Kai Rogers

Mentor: Wendy J. Maury, PhD

Year Entered Into Program: 2016

Terminal Degree9s) Received and Year: MD, PhD 2021

Affiliations

Microbiology | Medical Scientist Training Program

Research Description

The effect of macrophage polarization on Ebola virus infection

Ebola virus, a negative sense single stranded RNA virus and member of the Filoviridae family, is an important global pathogen responsible for episodic outbreaks of hemorrhagic fever causing tremendous morbidity and mortality. It is well appreciated that cells of the innate immune system, such as macrophages, are an important target population in the initial stages and sustainment of an Ebola virus infection. Previous research in our laboratory has shown that the stimulation of macrophages with the FDA-approved biologic, type 2 interferon (IFN-gamma), 24 hours prior to Ebola virus infection significantly reduced the permissivity of these cells to infection and concurrently reduced mortality in a mouse model. Others have shown that stimulation of macrophages with IFNγ2,3 classically activates this cell population, eliciting a proinflammatory M1 phenotype. These studies suggested the possibility that cytokineinduced activation of macrophages to an M1 versus an M2 phenotype may play an important role in determining the permissivity of the cells to Ebola virus infection, thereby altering the course of the disease. We hypothesized that human monocyte derived macrophages (hMDMs) or mouse peritoneal macrophages (MPMs) exposed to the M2 eliciting cytokines, such as IL-4 and IL-13, will be more susceptible to Ebola virus infection than non-activated macrophages or those exposed to the M1 eliciting cytokine, IFNγ. Preliminary studies support our hypothesis and we now seek to extend these studies.

Awards

  • Excellence in Conference Presentation Second Place: Genetics. Cell Biology and Anatomy (APSA)
  • Fellowship appointment on the Pharmacological Sciences Training Program (NIH T32 GM067795), University of Iowa, 2017-present
  • Institutional support on the Pharmacological Sciences Training Program (NIH T32 GM067795), University of Iowa, 2016-2017
  • The Richard G. Lynch, MD Award for Pathology, 2014
  • Mary Gates Research Endowment, 2013-2014
  • Herschel Roman Scholarship (Genome Sciences), 2012
  • UW-HHMI Integrative Research Internship Program, 2012

Publications

  1. Rogers KJ*, Van Ert HA*, Merrill A, et.al. Comparison of SARS-CoV2 binding and neutralizing antibody assays in COVID-19 plasma donors. Manuscript in preparation.
  2. Upton E*, Rogers KJ*, Luhmann E, Zhang Y, Colina A, Perlman S, Maury W, Radoshevich L. The ISGylome following beta-corona virus infection. Manuscript in preparation.
  3. Vijay R, Guthmiller J, Sturtz A, Crooks S, Johnsons J, Li L, Lan L, Pope R, Chen Y, Rogers KJ, Toombs J, Wilson M, Wilson PC, Maury W, Brekken RA, Butler N. Inflammation and hemolysis-associated phosphatidylserine exposure promote polyclonal plasmablast differentiation during infection. PNAS. Under review.
  4. Rogers KJ, Shtanko O, Vijay R, Mallinger LN, Joyner CJ, Galinski MR, Butler NS, Maury W.: Acute Plasmodium Infection Promotes Interferon-Gamma-Dependent Resistance to Ebola Virus Infection. Cell Rep. 30(12):4041-4051.e4, 2020.  PMCID: PMC7172281
  5. Vijay R, Guthmiller JJ, Sturtz AJ, Surette FA, Rogers KJ, Sompallae RR, Li F, Pope RL, Chan J, Rivera F, Andrew D, Webb L, Maury WJ, Xue H, Engwerda CR, McCarthy JS, Boyle MJ, Butler NS.: Infection-induced plasmablasts are a nutrient sink that impairs humoral immunity to malaria. Nat Immunol. 21(7):790-801, 2020.  PMCID: PMC7316608
  6. Rogers KJ, Jones-Burrage S, Maury W, Mukhopadhyay S.: TF protein of Sindbis virus antagonizes host type I interferon responses in a palmitoylation-dependent manner. Virology. 542:63-70, 2020.  PMCID: PMC7024065
  7. Rogers KJ, Shtanko O, Stunz LL, Malinger LN, Arkee T, Schmidt ME, Bohan D, Brunton B, White JM, Varga SM, Butler NS, Bishop GA, Maury W.: Frontline Science: CD40 signaling restricts RNA virus replication in Mϕs, leading to rapid innate immune control of acute virus infection. J Leukoc Biol. 2020 May 22. Doi: 10.1002/JLB.4HI0420-285RR. Online ahead of print. PMID: 32441445
  8. Rogers KJ, Brunton B, Mallinger L, Bohan D, Sevcik KM, Chen J, Ruggio N, Maury W.: IL-4/IL-13 polarization of macrophages enhances Ebola virus glycoprotein-dependent infection. PLoS Negl Trop Dis. 13(12):e0007819, 2019.  PMCID: PMC6905523
  9. Brunton B, Rogers K, Phillips EK, Brouillette RB, Bouls R, Butler NS, Maury W.:  TIM-1 serves as a receptor for Ebola virus in vivo, enhancing viremia and pathogenesis. PLoS Negl Trop Dis. 13(6):e0006983, 2019.  PMCID: PMC6615641 eCollection 2019 Jun.
  10. Rogers, K.J., Maury, W.:  The role of mononuclear phagocytes in Ebola virus infection.  J Leukoc Biol. 104(4):717-727, 2018. Review. PMID: 30095866
  11. Brouillette RB, Phillips EK, Patel R, Mahauad-Fernandez W, Moller-Tank S, Rogers KJ, Dillard JA, Cooney AL, Martinez-Sobrido L, Okeoma C, Maury W.:  TIM-1 Mediates Dystroglycan-Independent Entry of Lassa Virus.  J Virol 92(16):e00093-18, 2018.  PMCID: PMC6069209
  12. Rhein BA, Powers LS, Rogers K, Anantpadma M, Singh BK, Sakurai Y, Bair T, Miller-Hunt C, Sinn P, Davey RA, Monick MM and Maury W.:  Interferon-γ Inhibits Ebola Virus Infection. PLoS Pathogens, 11(11):e1005263, 2015.  PMCID: PMC4643030

 

Research