prof. Lindsey Devisscher (PhD)
Principal investigator - Gut-Liver Immunopharmacology unit, Dpt Basic and Applied Medical Sciences, Fac. Medicine and Health Science, Ghent University
Hepatocellular carcinoma (HCC) is the most common primary liver cancer and the second leading cause of cancer-related mortality worldwide. It’s an inflammation related cancer which generally develops in a background of chronic liver disease, characterized by continuous immune cell infiltration and release of pro-inflammatory mediators which are involved in malignant transformation. Macrophages dominate the chronic inflammatory microenvironment and aid in the transition of chronic inflammation to neoplastic transformation by the release of pro-inflammatory mediators. In addition, specific tumor-associated macrophages play a key role in tumor progression through the production of cytokines and growth factors involved in tumor growth, metastasis and invasion. One of our research topics include unraveling the contribution of different liver macrophage subsets to tumor initiation and growth and further investigating how we can target those specific macrophage subsets to enhance anti-tumor immunity and/or suppress tumor tolerance by using in vitro and in vivo models as well as human samples.
A major hurdle in cancer research, and biomedical research in general, is translation of results to the clinic. The most commonly used HCC models fail to represent the complex tumor microenvironment, are time consuming and do not allow timely and effective therapy evaluation. Therefore, our focus is set on developing human-based models including relevant orthotopic humanized mouse models and human sample based in vitro/ex vivo systems, essential for future immune-oncology studies and (immuno)therapy evaluation, as a leap forward to precision medicine.
- ‘Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches’. Cell. 2022 Jan 20;185(2):379-396.e38.
- ‘In Vivo and In Vitro Models of Hepatocellular Carcinoma: Current Strategies for Translational Modeling’. Cancers (Basel). 2021 Nov 8;13(21):5583.
- 'Characterization of the inflammatory microenvironment and hepatic macrophage subsets in experimental hepatocellular carcinoma models'. Oncotarget 12. 12:562-577.
- 'NOX1 inhibition attenuates the development of a pro-tumorigenic environment in experimental hepatocellular carcinoma'. Journal of Experimental & Clinical Cancer Research. 2021 Jan 23;40(1):40.
- 'Effect of isoform-specific HIF-1α and HIF-2α antisense oligonucleotides on tumorigenesis, inflammation and fibrosis in a hepatocellular carcinoma mouse model'. Oncotarget. 2020 Dec 1;11(48):4504-4520.
- 'Myeloid-specific IRE1alpha deletion reduces tumour development in a diabetic, non-alcoholic steatohepatitis-induced hepatocellular carcinoma mouse model'. Metabolism. 2020 Mar 31;107:154220.
- 'Unveiling the depletion of Kupffer cells in experimental hepatocarcinogenesis through liver macrophage subtype-specific markers'. J Hepatol. 2019 Jun 15. pii: S0168-8278(19)30187-4.
- 'Angiopoietin-2 promotes pathological angiogenesis and is a novel therapeutic target in murine non-alcoholic fatty liver disease'. Hepatology. 2018 Sep 26.
- 'Targeting the angio-proteostasis network: Combining the forces against cancer'. Pharmacology and Therapeutics, 2016. (PMID: 27452337)
- 'Next-generation proteasome inhibitor oprozomib synergizes with modulators of the unfolded protein response to suppress hepatocellular carcinoma.' Oncotarget, 2016. (PMID: 27167000)
- 'The role of macrophages in obesity-driven chronic liver disease'. Journal of Leukocyte Biology, 2016. (PMID: 26936934)
- 'Placental growth factor inhibition modulates the interplay between hypoxia and unfolded protein response in hepatocellular carcinoma.' BMC Cancer, 2016. (PMID: 26753564)
- Gut-Liver ImmunoPharmacology unit, Department Basic and Applied Medical Sciences, Corneel Heymanslaan 10, entrance 36, 9000 Ghent
- Lindsey.Devisscher@ugent.be; +32 9 332 56 65