Karen Jonscher, Ph.D.

Associate Professor, Harold Hamm Diabetes Center, Department of Biochemistry and Molecular Biology, OU Health Sciences Center


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.


Education:

MS, PhD California Institute of Technology, Pasadena, CA, Applied Physics
BS, University of Colorado, Boulder, CO, Engineering Physics


Selected Publications:

Friedman JE, Dobrinskikh E, Alfonso-Garcia A, Fast A, Janssen RC, Soderborg TK, Anderson AL, Reisz JA, D'Alessandro A, Frank DN, Robertson CE, de la Houssaye BA, Johnson LK, Orlicky DJ, Wang XX, Levi M, Potma EO, El Kasmi KC, Jonscher KR. Pyrroloquinoline quinone prevents developmental programming of microbial dysbiosis and macrophage polarization to attenuate liver fibrosis in offspring of obese mice. Hepatol Commun. 2018 Mar;2(3):313-328. PubMed PMID: 29507905.

Blaber EA, Pecaut MJ, Jonscher KR. Spaceflight Activates Autophagy Programs and the Proteasome in Mouse Liver. Int J Mol Sci. 2017 Sep 27;18(10) PubMed PMID: 28953266.

Jonscher KR, Stewart MS, Alfonso-Garcia A, DeFelice BC, Wang XX, Luo Y, Levi M, Heerwagen MJ, Janssen RC, de la Houssaye BA, Wiitala E, Florey G, Jonscher RL, Potma EO, Fiehn O, Friedman JE. Early PQQ supplementation has persistent long-term protective effects on developmental programming of hepatic lipotoxicity and inflammation in obese mice. FASEB J. 2017 Apr;31(4):1434-1448. PubMed PMID: 28007783; PubMed Central PMCID: PMC5349805.

Wesolowski SR, Kasmi KC, Jonscher KR, Friedman JE. Developmental origins of NAFLD: a womb with a clue. Nat Rev Gastroenterol Hepatol. 2017 Feb;14(2):81-96. PubMed PMID: 27780972.

Pecaut MJ, Mao XW, Bellinger DL, Jonscher KR, Stodieck LS, Ferguson VL, Bateman TA, Mohney RP, Gridley DS. Is spaceflight-induced immune dysfunction linked to systemic changes in metabolism? PLoS One. 2017;12(5):e0174174. PubMed PMID: 28542224; PubMed Central PMCID: PMC5443495.

Jonscher KR, Alfonso-Garcia A, Suhalim JL, Orlicky DJ, Potma EO, Ferguson VL, Bouxsein ML, Bateman TA, Stodieck LS, Levi M, Friedman JE, Gridley DS, Pecaut MJ. Spaceflight Activates Lipotoxic Pathways in Mouse Liver. PLoS One. 2016;11(4):e0152877. PubMed PMID: 27097220; PubMed Central PMCID: PMC4838331.

Kendrick AA, Choudhury M, Rahman SM, McCurdy CE, Friederich M, Van Hove JL, Watson PA, Birdsey N, Bao J, Gius D, Sack MN, Jing E, Kahn CR, Friedman JE, Jonscher KR. Fatty liver is associated with reduced SIRT3 activity and mitochondrial protein hyperacetylation. Biochem J. 2011 Feb 1;433(3):505-14. PubMed PMID: 21044047; PubMed Central PMCID: PMC3398511.

Renner B, Tong HH, Laskowski J, Jonscher K, Goetz L, Woolaver R, Hannan J, Li YX, Hourcade D, Pickering MC, Holers VM, Thurman JM. Annexin A2 Enhances Complement Activation by Inhibiting Factor H. J Immunol. 2016 Feb 1;196(3):1355-65. PubMed PMID: 26729803; PubMed Central PMCID: PMC4724541.

Klawitter J, Klawitter J, Kushner E, Jonscher K, Bendrick-Peart J, Leibfritz D, Christians U, Schmitz V. Association of immunosuppressant-induced protein changes in the rat kidney with changes in urine metabolite patterns: a proteo-metabonomic study. J Proteome Res. 2010 Feb 5;9(2):865-75. PubMed PMID: 19994912; PubMed Central PMCID: PMC3955702.

Jin L, Waterman PM, Jonscher KR, Short CM, Reisdorph NA, Cambier JC. MPYS, a novel membrane tetraspanner, is associated with major histocompatibility complex class II and mediates transduction of apoptotic signals. Mol Cell Biol. 2008 Aug;28(16):5014-26. PubMed PMID: 18559423; PubMed Central PMCID: PMC2519703.

Lambert C, Li J, Jonscher K, Yang TC, Reigan P, Quintana M, Harvey J, Freed BM. Acrolein inhibits cytokine gene expression by alkylating cysteine and arginine residues in the NF-kappaB1 DNA binding domain. J Biol Chem. 2007 Jul 6;282(27):19666-75. PubMed PMID: 17491020.

Resing KA, Meyer-Arendt K, Mendoza AM, Aveline-Wolf LD, Jonscher KR, Pierce KG, Old WM, Cheung HT, Russell S, Wattawa JL, Goehle GR, Knight RD, Ahn NG. Improving reproducibility and sensitivity in identifying human proteins by shotgun proteomics. Anal Chem. 2004 Jul 1;76(13):3556-68. PubMed PMID: 15228325.

Lewis TS, Hunt JB, Aveline LD, Jonscher KR, Louie DF, Yeh JM, Nahreini TS, Resing KA, Ahn NG. Identification of novel MAP kinase pathway signaling targets by functional proteomics and mass spectrometry. Mol Cell. 2000 Dec;6(6):1343-54. PubMed PMID: 11163208.

Jonscher KR, Yates JR 3rd. The quadrupole ion trap mass spectrometer--a small solution to a big challenge. Anal Biochem. 1997 Jan 1;244(1):1-15. PubMed PMID: 9025900.