The impact of macrophages on metabolic and malignant pathologies: Understanding the role of sex differences

Macrophages, cells of the innate immune system, play an important role in the regulation of metabolic and malignant diseases. Depending on whether macrophages have an inflammatory or regulatory phenotype, they can either promote or inhibit disease progression. Metabolic and malignant diseases have a different prevalence and prognosis between the sexes. Macrophages appear to play a role in these differences, and their gene expression shows the strongest differences between the sexes of all immune cell types.

The aim of our work is to contribute to the understanding of the mechanisms underlying these differences. We use in vitro models of primary human and murine macrophages as well as in vivo models of metabolic and malignant diseases. A particular focus is on epigenetic processes.

Portraitfoto von Prof. Dr. Alexandra K. Kiemer

Project lead

Univ.-Prof. Dr. Alexandra K. Kiemer

Saarland University
Institute of Pharmaceutical Biology

Pharm.bio.kiemer(at)mx.uni-saarland.de
ORCID: 0000-0002-7224-9900

Curriculum Vitae

 

Important publications

  1. Kendzia S, Franke S, Kröhler T, Golob-Schwarzl N, Schweiger C, Toeglhofer AM, Wodlej C, Bergler H, Pertschy B, Uranitsch S, Holte M, El-HeliebiA, Fuchs J, Punschart A, Stiegler P, Keil M, Hoffmann J, Henderson D. Lehrach H, Yaspo M-L, Reinhard C, Keilholz U, Regenbrecht C, Schicho R, Fickert P, Lax S, Erdmann F, Schulz MH, Kiemer AK, Haybaeck J, Kessler SM. 2023. A combined computational and functional approach identifies IGF2BP2 as a driver of chemoresistance in a wide array of pre-clinical models of colorectal cancer. Mol Cancer 22:89, doi: 10.1186/s12943-023-01787-x
  2. Al-Fityan S, Diesel B, Fischer T, Empofo E, Schomisch A, Mashayekhi V, Schneider M, Kiemer AK. 2023. Nanostructured microparticles repolarize macrophages and induce cell death in an in vitro model of tumour-associated macrophages. Pharmaceutics 15:1895, 10.3390/pharmaceutics15071895
  3. Schymik HS, Dahlem C, Barghash A, Kiemer AK. 2022. Comment on: The m6A reader IGF2BP2 regulates macrophage phenotypic activation and inflammatory diseases by stabilizing TSC1 and PPARγ. AdvSci 2104372, doi: 10.1002/advs.202104372
  4. Köhler N, Höring M, Czepukojc B, Rose TD, Buechler C, Kröhler T, Hayback J, Liebisch G, Pauling J, Kessler SM, Kiemer AK. 2022. Kupffer cells are protective in alcoholic steatosis. Biochim Biophys Acta Mol Basis Dis 1868:166398, doi: 10.1016/j.bbadis.2022.166398
  5. Hoppstädter J, Dembek A, Höring M, Liebisch G, Dahlem C, Sultan A, Wirth N, Al-Fityan S, Diesel B, Gasparoni G, Walter J, Helms V, Huwer H, Simon M, Schulz MH, Kiemer AK. 2021. Dysregulation of cholesterol homeostasis in human lung cancer tissue and tumor-associated macrophages. EBioMedicine 72: 103578, doi: 10.1016/j.ebiom.2021.103578
  6. Dahlem C, Siow WX, Lopatniuk M, Fai Tse WK, Kessler SM, Kirsch SH, Hoppstädter J, Vollmar, AM, Müller R, Luzhetskyy A, Bartel K, Kiemer AK. 2020. Thioholgamide A, a new anti-proliferative anti-tumor agent, modulates macrophage polarization and metabolism. Cancers 12:1288, doi: 10.3390/cancers12051288
  7. Valbuena Perez JV, Linnenberger R, Dembek A, Bruscoli S, Riccardi C, Schulz MH, Meyer MR, Kiemer AK, Hoppstädter J. 2020. Altered glucocorticoid metabolism represents a feature of macroph-aging. Aging Cell 19:e13156, doi: 10.1111/acel.13156
  8. Kessler SM, Hoppstädter J, Hosseini K, Laggai S, Haybaeck J, Kiemer AK. Lack of Kupffer cell depletion in diethylnitrosamine-induced hepatic inflammation. J Hepatol 2019; 70:175-7, doi: 10.1016/j.jhep.2018.11.018
  9. Kröhler T, Kessler SM, Hosseini K, List M, Barghash A, Patial S, Laggai S, Gemperlein K, Haybäck J, Müller R, Helms V, Schulz MH, Hoppstädter J, Blackshear PJ, Kiemer AK. 2019. The mRNA-binding protein TTP in hepatocarcinogenesis and hepatocellular carcinoma. Cancers 11:1754, doi: 10.3390/cancers11111754
  10. Hoppstädter J, Seif M, Dembek A, Cavelius C, Huwer H, Kraegeloh A, Kiemer AK. 2015. M2 polarization enhances silica nanoparticle uptake by macrophages. Front Pharmacol 6:55, doi: 10.3389/fphar.2015.00055