Karen Jonscher, PhD

  • Position: Associate Professor, Biochemistry & Molecular Biology, Diabetes Research Member

Biography

The central focus of my research is on understanding why a mother’s obesity primes her child in utero to increase risk for developing metabolic disease in later life and how a novel antioxidant, pyrroloquinoline quinone (PQQ), acts to protect metabolic health. We use a systems biology, multi-omics approach to investigate interactions between the gut microbiome and the innate immune system that lead to oxidative stress and inflammatory liver injury. Our current work uses transgenic mice to study the role of reprogrammed cellular metabolism in impairing macrophage function and both pre- and probiotic strategies to improve gut microbial function in offspring of obese mice.

Another arm of our research focuses on the response of the cardiometabolic system to the space environment. We have found that even short duration exposure to space results in activation of pro-inflammatory and pro-fibrotic programs in mouse livers, as well as alterations in cellular senescence. We seek to determine whether PQQ supplementation might prevent these changes using ground-based models of spaceflight, such as hindlimb unloading and low dose/low dose rate radiation exposure. Results from our studies will be used to assess risk to astronaut cardiometabolic health during a mission to Mars and the efficacy of a readily available dietary supplement, safe for human use, as a countermeasure.

Email

Karen-Jonscher@ouhsc.edu

Additional Websites

Health Education
  • Graduate School
  • Postdoctoral Training, Proteomics National Jewish Medical Center
    Denver, CO
  • Postdoctoral Studies, Proteomics University of Colorado Boulder
    Boulder, CO
  • Master's Degree in Applied Physics California Institute of Technology
    Pasadena, CA
  • Undergraduate School
  • Bachelor's Degree in Engineering Physics University of Colorado
    Boulder, CO
Research Interests:
  • Determining the roles of the macrophage and microbiota in developmental programming of nonalcoholic fatty liver disease in offspring of obese mothers.
  • Investigating the role of cellular senescence in the developmental programming of NAFLD and the potential senolytic action of pyrroloquinoline quinone (PQQ).
  • Elucidating mechanisms by which PQQ activates protective signaling networks in obesity to suppress hepatic fibrosis and steatosis in developmentally programmed NAFLD.
  • Understanding the role of aryl hydrocarbon receptor signaling, induced by indole and indole-3-acetate, in protecting offspring of obese mothers from development of NAFLD.
  • Identifying epigenetic changes in liver, fat and immune cells associated with metabolic disease progression. Characterizing epigenetic modifications induced by exposure to maternal dietary supplements (PQQ, indole, indole-3-acetate) and associated with hepatoprotection.
  • Unraveling mechanisms by which exposure to the space environment alters hepatic and immune function and impairs systemic metabolism.
Publications
  • Pyrroloquinoline-Quinone Is More Than an Antioxidant: A Vitamin-like Accessory Factor Important in Health and Disease Prevention 2021

    Biomolecules. 2021 Sep 30;11(10):1441. doi: 10.3390/biom11101441. PMID: 34680074; PMCID: PMC8533503.

  • Pyrroloquinoline quinone prevents developmental programming of microbial dysbiosis and macrophage polarization to attenuate liver fibrosis in offspring of obese mice. 2018

    Hepatol Commun. 2018 Mar;2(3):313-328. PubMed PMID: 29507905.

  • Spaceflight Activates Autophagy Programs and the Proteasome in Mouse Liver. 2017

    Int J Mol Sci. 2017 Sep 27;18(10) PubMed PMID: 28953266.

  • Early PQQ supplementation has persistent long-term protective effects on developmental programming of hepatic lipotoxicity and inflammation in obese mice. 2017

    FASEB J. 2017 Apr;31(4):1434-1448. PubMed PMID: 28007783; PubMed Central PMCID: PMC5349805.

  • Spaceflight Activates Lipotoxic Pathways in Mouse Liver. 2016

    PLoS One. 2016;11(4):e0152877. PubMed PMID: 27097220; PubMed Central PMCID: PMC4838331.

  • Fatty liver is associated with reduced SIRT3 activity and mitochondrial protein hyperacetylation. 2011

    Biochem J. 2011 Feb 1;433(3):505-14. PubMed PMID: 21044047; PubMed Central PMCID: PMC3398511.

  • Improving reproducibility and sensitivity in identifying human proteins by shotgun proteomics. 2004

    Anal Chem. 2004 Jul 1;76(13):3556-68. PubMed PMID: 15228325.

  • Identification of novel MAP kinase pathway signaling targets by functional proteomics and mass spectrometry. 2000

    Mol Cell. 2000 Dec;6(6):1343-54. PubMed PMID: 11163208.

  • Matrix-assisted laser desorption ionization/quadrupole ion trap mass spectrometry of peptides. 1997

    Application to the localization of phosphorylation sites on the P protein from Sendai virus. J Biol Chem. 1997 Jan 17;272(3):1735-41. PubMed PMID: 8999854.

  • Mixture analysis using a quadrupole mass filter/quadrupole ion trap mass spectrometer 1996

    Anal Chem. 1996 Feb 15;68(4):659-67. PubMed PMID: 8999740.