Digestive Health Center

  • Obesity and the Digestive System

    Anja Jaeschke, PhD
    Assistant Professor
    Department of Pathology and Laboratory Medicine

    Description of Research

    The overall aim of Dr. Jaeschke’s laboratory is to investigate the role of stress-activated protein kinases in metabolic signal transduction. Metabolic syndrome, which is associated with obesity, insulin resistance, type 2 diabetes, and non-alcoholic fatty liver disease (NAFLD), is a major health problem world-wide. The cJun-NH2-stress-activated kinase (JNK) pathway is emerging as important player in the development of obesity-induced insulin resistance and NAFLD. Her major goal is to obtain deeper knowledge of the mechanism by which obesity regulates the JNK pathway and how this pathway is involved in the control of metabolic diseases. She has recently shown that mixed-lineage kinase 3 (MLK3) functions as an upstream mediator of JNK activation by free fatty acids. Using knockout mice in which the gene for MLK3 has been ablated, Dr. Jaeschk is investigating the activation mechanism and biological significance of MLK3 in the development of NAFLD. All studies involve a combination of molecular biology and biochemical techniques as well as in vitro (tissue culture) and in vivo systems.

    Collaborations

    Dr. Jaeschke works with Dr. Woollett on the role of insulin signaling and MAPK in the regulation of placental nutrient transport. Additionally, she collaborates with Dr. Hui examining the role of stress-activated kinases and the scaffold protein JIP in apolipoprotein E receptor-2 (apoER2) function, and with Dr. Tso studying stress activated kinases and NF-κB in regulation of inflammatory cytokine secretion. Anticipated Core Use: Gene and Protein Expression, Bioinformatics, and Integrative Morphology Cores.

 
  • Research image.

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    Research image.

    Livers from WT and MLK3-/- mice maintained on a standard diet (chow) or on a high fat diet (HFD). Representative histological sections stained with hematoxylin and eosin from wild-type and Mlk3-/- mice (left panel). JNK activity was measured in a kinase assay (KA) using [g-32P]ATP and c-Jun as substrates.  Figure from a manuscript submitted for publication