Education:
1989 BS University of Colorado, Boulder, CO
1996 PhD California Institute of Technology, Pasadena, CA
2000 Postdoc National Jewish Research Center, Denver, CO
2002 Postdoc University of Colorado, Boulder, CO
Clinical/Research Interests:
Maternal obesity affects the developing embryo and fetus in ways that lead to increased vulnerability for chronic disease in later life. Understanding how a mother’s obesity primes her child in utero to increase risk for developing metabolic-associated steatotic liver disease (MASLD) in later life is a critical question with significant relevance to human health. My long-term goal is to identify dietary interventions that, when given during pregnancy and/or lactation, halt developmental programming of metabolic disease risk in offspring. My early training in Applied Physics and mass spectrometry-based ‘omics allows me to apply large-scale, interdisciplinary, systems biology-based approaches to this work. Our lab made the novel discovery that a dietary antioxidant, pyrroloquinoline quinone (PQQ), provides juvenile offspring of obese mouse dams consuming a “Western-style” diet (WD) with remarkable protection from maternal diet-induced hepatic steatosis and fibrosis. Furthermore, hepato-protection is recapitulated in germ-free recipients of fecal microbial transfer, suggesting PQQ, a known bacterial co-factor, impacts the microbiome; recent data suggest xenobiotic metabolism is a key pathway targeted by PQQ. My work uses the state-of-the-art molecular, metabolic, and imaging technologies in a variety of animal models.
My current R01-supported projects investigate the mechanisms for PQQ’s impact on the fetal and neonatal hematopoietic stem and progenitor cells and innate immune cell programming in mouse and nonhuman primate models of maternal obesity. The protective effect of PQQ is evident in mouse offspring liver and bone marrow, even when PQQ is only supplemented to the dams during gestation and lactation, suggesting this potent antioxidant modulates epigenetic change, beginning in utero. Our work in a highly translational obese nonhuman primate model (Olive baboon), allows us to investigate the fetal mechanisms related to developmental programming and PQQ’s action in utero, which is not possible in rodent models. Our preliminary data in non-pregnant obese adult female baboons showed that once daily oral PQQ improves systemic inflammation and metabolism. We also are developing a nonhuman primate model of paternal obesity. Although PQQ is available for human use over the counter and has been shown to be safe, our long-term goal is to test the efficacy of PQQ for use in obese pregnancy. Findings from our studies in mice and nonhuman primates are critical to elucidate the role of innate immunity in developmental programming, advance novel therapeutics, and protect obese mothers and their children from MASLD.
Funding:
NIDDK - R01DK139443
Evaluating PQQ for preventing maternal obesity-induced fetal programming of juvenile NAFLD in Papio anubis
MPI: Corresponding PI JONSCHER, Karen
In this project we seek to determine whether maternal treatment with PQQ during obese pregnancy improves maternal and placental inflammation and ameliorates NAFLD and metabolic disorders in juvenile offspring.
NIDDK - 1R01DK121951
Role of the macrophage in developmentally programmed NAFLD
MPI: JONSCHER, Karen; Corresponding PI: Friedman, JE
This mouse-based project seeks to identify early microbial factors priming metabolic and epigenetic changes in innate immune cells and mechanisms by which a dietary antioxidant, PQQ, protects offspring cells from inflammatory activation and attenuates NAFLD.
HHDC Pilot Project
Maternal Macrophage Immunotherapy: A Novel Strategy to Prevent Developmental Programming of Metabolic Disease in Obese Pregnancy
PI: CLEGG, J.; co-I: JONSCHER, Karen
This project seeks to prototype a nanoscale drug-delivery device that is internalized by myeloid-derived cells for IV injection into pregnant mice.
PHF Team Science Grant
Development of a Baboon (Papio anubis) Model of Western Diet and Paternal Obesity- Mechanisms for Fetal/Offspring Epigenetic Programming of Metabolic Disorders
PI: MYERS, D; co-I: JONSCHER, Karen
We aim to use an olive baboon model to test the effects of paternal obesity and consumption of a Western-style diet on sperm DNA methylation and non-coding RNA expression patterns, fetal hepatic steatosis, periportal fibrosis, and inflammation, and altered placental trophoblast gene expression, placental vascular development and inflammation at 0.9 gestation.
Select Honors and Accomplishments:
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2019
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Friedman, et al. paper was a “Top Downloaded Paper”, Hepatology Communications
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2014
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Kendrick et al. paper was the “Most Cited Paper”, Biochemical Journal
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2013
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Distinguished Service Award, Association of Biomolecular Resource Facilities
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2012
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Kendrick et al. paper was one of the “Most Downloaded Papers”, Biochemical Journal
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2012
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Distinguished Service Award, University of Colorado Faculty Council
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2007
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ABRF 2007 Outstanding Scientists and Technologists Award, Association of Biomolecular Resource Facilities
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2007
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Eugene M. Farber Travel Award for Young Investigators, Society of Investigative Dermatology
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Select Publications:
Castillo-Castrejon M, McClurg HE, Maxted MF, Myers DA, Jonscher K.R. A Role for the Antioxidants Coenzyme Q10 and Pyrroloquinoline Quinone in Mitigating Obesity-Associated Reproductive Dysfunction†. Biol Reprod. 2025 Aug 14;. doi: 10.1093/biolre/ioaf185. [Epub ahead of print] PubMed PMID: 40810470.
Gershner GH, Golubkova A, Dalton C, Schlegel C, Calkins C, Reuter DN, Learner M, Papin JF, Gurung S, Jonscher K.R., Myers DA, Hunter CJ. Maternal Western diet increases inflammatory markers and decreases barrier function of offspring in Papio anubis. Am J Physiol Gastrointest Liver Physiol. 2025 Aug 1;329(2):G344-G359. doi: 10.1152/ajpgi.00342.2024. Epub 2025 Jul 10. PubMed PMID: 40637163.
Sugino, K. Y., Janssen, R. C., McMahan, R. H., Zimmerman, C., Friedman, J. E., Jonscher, K. R. (2024). Vertical Transfer of Maternal Gut Microbes to Offspring of Western Diet-Fed Dams Drives Reduced Levels of Tryptophan Metabolites and Postnatal Innate Immune Response. Nutrients, 16(12), 1808. PMID: 38931163. DOI: 10.20944/preprints202405.0842.v1
Sugino, K. Y., Mandala, A., Janssen, R. C., Gurung, S., Trammell, M., Day, M. W., Brush, R. S., Papin, J. F., Dyer, D. W., Agbaga, M.-P., Friedman, J. E., Castillo-Castrejon, M., Jonscher, K. R., Myers, D. A. (2022). Western diet-induced shifts in the maternal microbiome are associated with altered microRNA expression in baboon placenta and fetal liver. Frontiers in Clinical Diabetes and Health Care, 3. DOI: 10.1101/2022.05.18.492490
Zhang, L., Jonscher, K. R., Zhang, Z., Xiong, Y., Mueller, R. S., Friedman, J. E., Pan, C. (2022). Islet autoantibody seroconversion in type-1 diabetes is associated with metagenome-assembled genomes in infant gut microbiomes. Nature Communications, 13(1). DOI: 10.1038/s41467-022-31227-1
Friedman, J. E., Dobrinskikh, E., Alfonso‐Garcia, A., Fast, A., Janssen, R. C., Soderborg, T. K., Anderson, A. L., Reisz, J. A., D'Alessandro, A., Frank, D. N., Robertson, C. E., de la Houssaye, B. A., Johnson, L. K., Orlicky, D. J., Wang, X. X., Levi, M., Potma, E. O., El Kasmi, K. C., Jonscher, K. R. (2018). Pyrroloquinoline quinone prevents developmental programming of microbial dysbiosis and macrophage polarization to attenuate liver fibrosis in offspring of obese mice. Hepatology Communications, 2(3), 313-328. DOI: 10.1002/hep4.1139
Jonscher, K. R., Stewart, M. S., Alfonso‐Garcia, A., DeFelice, B. C., Wang, X. X., Luo, Y., Levi, M., Heerwagen, M. J., Janssen, R. C., Houssaye, B. A., Wiitala, E., Florey, G., Jonscher, R. L., Potma, E. O., Fiehn, O., Friedman, J. E. (2017). Early PQQ supplementation has persistent long‐term protective effects on developmental programming of hepatic lipotoxicity and inflammation in obese mice. The FASEB Journal, 31(4), 1434-1448. DOI: 10.1096/fj.201600906r
A complete list of publications can be found on MyBibliography: https://www.ncbi.nlm.nih.gov/sites/myncbi/1Tk39bbxldlAt/bibliography/47670707/