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.
Another focus involves the role of cancer stem cells (CSCs) in the pathogenesis of HCC. It has been postulated that only a minor fraction of tumor cells can initiate a new tumor. Those cells share common features with somatic stem cells and have been termed cancer stem cells (CSCs). CSCs are believed to be the tumor-initiating cells through their capacity of self-renewal and production of heterogeneous progeny. In addition, they are naturally resistant to chemo/radiotherapy because of their quiescence and intrinsic biochemical defense mechanisms. Hence, CSCs are believed to be responsible for the initiation and propagation of tumors as well as relapse after therapy. In HCC, CSC markers are linked to poor prognosis, including increased invasion and metastasis. Our research focuses on the exploitation of (1) stemness/progenitor signaling pathways to target CSCs and (2) CSCs as immunotherapy in HCC by using mouse models, in vitro assays and human samples.
- dr. Sander Lefere (MD, PhD) - post-doctoral researcher
- Kevin De Muynck - doctoral fellow
- Bart Vanderborght - doctoral fellow
- Eva Gijbels - doctoral fellow
- Lander Heyerick - doctoral fellow
- Danielle Woods - secretaris
- Inge Van Colen - lab technician
- Els Van Deynse - lab technician
- '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)
University Hospital Ghent, Hepatology Research Unit, Corneel Heymanslaan 10, Building B, second floor, 9000 Ghent