Fibrosis and Tissue Repair

Our current research interest is fibrogenesis with focus on Hepatic Stellate Cell behaviour in liver fibrosis and liver cancer cell biology with a specific focus on fibrotic stroma - cancer cell interaction. Further interests include genetic polymorphism heterogeneity - cell behaviour in diseases such as Non-Alcoholic Fatty Liver Disease and Non-Alcoholic Steatohepatitis and cancer development.

The Team’s research remit covers both identifying/characterization of human organ specific Extracellular Matrix and cellular components of tissues, with a specific focus on cell behaviour in 2D and 3D cell culture systems for improvement of new target identification and drug development. 

Together with the ENETS oncology team of the Royal Free Hospital we are exploring mesenteric fibrosis in small intestinal neuroendocrine tumours:

• pathogenesis and potential therapeutic targets
• early biomarker detection in mesenteric fibrosis
• Deep Sequencing of gastroenteropancreatic neuroendocrine carcinoma.

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1. Maria Inês Castanho Martins
2. Saiji Kathiresu Nageshwaran
3. Giulia Lupo

1. Al-Akkad W, Acedo P, Vilia MG ... Hall AR ... Luong TV, Whittaker SR, Pereira SP, Vallier L, Pinzani M, Rombouts K, Mazza G (2022). Tissue-Specific Human Extracellular Matrix Scaffolds Promote Pancreatic Tumour Progression and Chemotherapy Resistance. Cells. 2022 Nov 17;11(22):3652.

2. Thanapirom K, Caon E, Papatheodoridi M, Frenguelli L, Al-Akkad W, Zhenzhen Z, Vilia MG, Pinzani M, Mazza G, Rombouts K (2021). Optimization and Validation of a Novel Three-Dimensional Co-Culture System in Decellularized Human Liver Scaffold for the Study of Liver Fibrosis and Cancer. Cancers (Basel). 2021 Sep 30;13(19):4936.

3. Laskaratos FM, Levi A, Schwach G, Pfragner R, Hall A, Xia D, von Stempel C ... Luong TV, Toumpanakis C, Mandair D, Caplin M, Rombouts K (2021). Transcriptomic Profiling of In Vitro Tumor-Stromal Cell Paracrine Crosstalk Identifies Involvement of the Integrin Signaling Pathway in the Pathogenesis of Mesenteric Fibrosis in Human Small Intestinal Neuroendocrine Neoplasms. Frontiers Oncology. 2021 Feb 24;11:629665. eCollection 2021.

4. Dat NQ, Thuy LTT, Hieu VN ... Rombouts K, Dong MP, Hanh NV ... Pinzani M, Kawada N (2021). Hexa Histidine-Tagged Recombinant Human Cytoglobin Deactivates Hepatic Stellate Cells and Inhibits Liver Fibrosis by Scavenging Reactive Oxygen Species. Hepatology. 2021 Jun;73(6):2527-2545. Epub 2021 May 22. Erratum in: Hepatology. 2022 Dec;76(6):1902.

5. Böttcher K, Longato L, Marrone G, Mazza G, Ghemtio L, Hall A, Luong TV, Caruso S, Viollet B, Zucman-Rossi J, Pinzani M, Rombouts K (2021). AICAR and compound C negatively modulate HCC-induced primary human hepatic stellate cell activation in vitro. Am J Physiol Gastrointest Liver Physiol. 2021 Apr 1;320(4):G543-G556.

6. Pavlović N, Calitz C, Thanapirom K, Mazza G, Rombouts K, Gerwins P, Heindryckx F (2020). Inhibiting IRE1α-endonuclease activity decreases tumor burden in a mouse model for hepatocellular carcinoma. Elife. 2020 Oct 26;9:e55865.

7. Zanieri F, Levi A, Montefusco D ... Luong TV ... Mazza G, Argemi J, Bataller R, Cowart LA, Kester M, Pinzani M, Rombouts K (2020). Exogenous Liposomal Ceramide-C6 Ameliorates Lipidomic Profile, Energy Homeostasis, and Anti-Oxidant Systems in NASH. Cells. 2020 May 16;9(5):1237.

8. Okina Y, Sato-Matsubara M, Matsubara T, Daikoku A, Longato L, Rombouts K ... Pinzani M, Kawada N. TGF-β1-driven reduction of cytoglobin leads to oxidative DNA damage in stellate cells during non-alcoholic steatohepatitis. Journal of Hepatology. 2020 Apr 17. pii: S0168-8278(20)30228-2.

9. Barcena-Varela M, Paish H, Alvarez L ... Rombouts K, Oakley F, Mann J, et al (2020). Epigenetic mechanisms and metabolic reprogramming in fibrogenesis: dual targeting of G9a and DNMT1 for the inhibition of liver fibrosis. Gut. 2020 Apr 23. pii: gutjnl-2019-320205.

10. Kostrzewski T, Maraver P, Ouro-Gnao L, Levi A, Snow S, Miedzik A, Rombouts K*, Hughes D* (2019). A Microphysiological System for Studying Nonalcoholic Steatohepatitis. Hepatology Communication. 2019 Nov 13;4(1):77-91. eCollection 2020 Jan. (*Contributed equally)

11. Mazza G, Telese A, Al-Akkad W, Frenguelli L, Levi A ... Hall AR, Godovac-Zimmermann J, Luong TV, De Coppi P, Pinzani M, Rombouts K (2019). Cirrhotic Human Liver Extracellular Matrix 3D Scaffolds Promote Smad-Dependent TGF-β1 Epithelial Mesenchymal Transition. Cells. 2019 Dec 28;9(1). pii: E83.

12. Laskaratos FM, Mandair D, Hall A, Alexander S, von Stempel C, Bretherton J, Luong T, Watkins J, Ogunbiyi O, Rombouts K, Caplin M, Toumpanakis C (2020). Clinicopathological correlations of mesenteric fibrosis and evaluation of a novel biomarker for fibrosis detection in small bowel neuroendocrine neoplasms. Endocrine. 2020 Mar;67(3):718-726.

13. De Chiara F, Thomsen KL, Habtesion A ... Hall A, Andreola F, Paish HL, Reed LH, Watson AA, Leslie J, Oakley F, Rombouts K, et al (2020). Ammonia Scavenging Prevents Progression of Fibrosis in Experimental Nonalcoholic Fatty Liver Disease. Hepatology. 2020 Mar;71(3):874-892.

14. Giuffrida P, Curti M, Al-Akkad W, Biel C, Crowley C, Frenguelli L, Telese A, Hall A ... Pinzani M, Di Sabatino A, *Rombouts K, *Mazza G (2019). Decellularized Human Gut as a Natural 3D Platform for Research in Intestinal Fibrosis. Inflamm Bowel Dis. 2019 Oct 18;25(11):1740-1750. (*Contributed equally.)

15. Marrone G, De Chiara F, Böttcher K, Levi A, Dhar D, Longato L, Mazza G, Zhang ZZ, Marrali M, Fernández-Iglesias A, Hall A, Luong TV, Viollet B, Pinzani M, Rombouts K (2018). The adenosine monophosphate-activated protein kinase-vacuolar adenosine triphosphatase-pH axis: A key regulator of the profibrogenic phenotype of human hepatic stellate cells. Hepatology. 2018 Sep;68(3):1140-1153.

16. Böttcher K, Rombouts K, Saffioti F, Roccarina D, Rosselli M, Hall A, Luong TV, Tsochatzis EA, Thorburn D, Pinzani M (2018). MAIT cells are chronically activated in patients with autoimmune liver disease and promote profibrogenic hepatic stellate cell activation. Hepatology. 2018 Jul;68(1):172-186.

17. Mazza G, Al-Akkad W, Telese A, Longato L, Urbani L, Robinson B, Hall A ... Rombouts K, Pinzani M (2017). Rapid production of human liver scaffolds for functional tissue engineering by high shear stress oscillation-decellularization. Scientific Report. 2017 Jul 17;7(1):5534. PubMed PMID: 28717194

18. Carloni V, Lulli M, Madiai S, Mello T, Hall A, Luong TV, Pinzani M, *Rombouts K, *Galli A (2017). CHK2 overexpression and mislocalisation within mitotic structures enhances chromosomal instability and hepatocellular carcinoma progression. Gut. 2018 Feb;67(2):348-361.

19. Longato L, Andreola F, Davies SS, Roberts JL, Fusai G, Pinzani M, Moore K, Rombouts K (2017). Reactive gamma-ketoaldehydes as novel activators of hepatic stellate cells in vitro. Free Radic Biol Med. 2017 Jan;102:162-173.

20. Jalan R, De Chiara F, Balasubramaniyan V, Andreola F, Khetan V, Malago M, Pinzani M, Mookerjee RP, Rombouts K (2016). Ammonia produces pathological changes in human hepatic stellate cells and is a target for therapy of portal hypertension. Journal of Hepatology. 2016 Apr;64(4):823-33.

Contact details

• Email: Prof. Krista Rombouts (k.rombouts@ucl.ac.uk)

Address

Division of Medicine, Institute for Liver and Digestive Health  
UCL Medical School
Upper 3rd Floor Royal Free Hospital
LONDON
NW3 2QG