Permanent Members
In the lab we develop novel models to study the mechanism of organ fibrosis. In addition, these models are used to test new antifibrotic compounds.
Postdocs
PhD students
By using precision-cut pulmonary slices, Kurnia SS Putri is now studying lung fibrosis, testing drugs with various mechanism of actions (antifibrotic-macrophage stimulating compounds and TGFb-inhibiting drug) for lung fibrosis, and exploring regulation of osteoprotegerin in organ fibrosis.
My research is focused on the improvement of the stability of proteins using sugar glass technology during the production processes of polymeric formulations for controlled and sustained release. This knowledge is applied to the development of polymeric sustained release formulations for PDGF-receptor targeted proteins, which can be used in the treatment of fibrosis.
The ZonMW project “Use of human and animal tissue slices for the development of anti-fibrotic compounds” is focused on clinical translation, i.e., validation of precision-cut tissue slices (PCTS) ex vivo model against in vivo models, as well as on anti-inflammatory and anti-fibrotic drug development with our industrial partner, Boehringer Ingelheim. By using animal and human PCTS, we contribute to the reduction and replacement of the number of animals used in the drug development process, thereby resulting in substantial contribution to the 3Rs. Furthermore, the current project promises to explore the mechanisms of fibrosis reversal and progression that might lead to the novel targets for anti-fibrotic drugs in human disease.
My PhD project is about intestinal fibrosis, particularly in Crohn’s disease (CD). I use the precision-cut slice model to study the effect of cigarette smoke on fibrosis healthy and CD-affected intestine. Furthermore, I try to unravel which layers of the intestinal wall contribute the most to narrowing of the lumen by stimulating slices from different regions and layers with various pro-fibrotic cytokines. Besides that, I focus on serological biomarkers for extracellular matrix remodelling in CD and in response to treatment.
Chronic inflammation or injury in the gut can lead to intestinal fibrosis, and is characterized by excessive deposition of extracellular matrix components like collagen and fibronectin. Finally, this will lead to stricture formation due to narrowing of the lumen. Current therapeutic options against fibrotic strictures are surgery and repeated mechanical palliation. Despite multiple studies, there are no antifibrotic therapies, yet. My project is focused on possible antifibrotic drugs for intestinal fibrosis. In addition, formulation of the antifibrotic drugs will be developed that allows specific delivery to the intestinal strictures.
An ex vivo model to study the gut-liver axis in liver fibrosis
Liver fibrosis ultimately results in structural and functional liver deterioration and loss of function.
Blood from the gut ends up via the portal vein in the liver, therefore via this so called gut liver-axis the potential fibrotic microbial products (lipopolysaccharide, lipoteichoic acid, etc.), the PAMPs, can easily reach the liver leading to early-onset of fibrosis.
In this project, more knowledge on the mechanism of liver fibrosis under PAMPs stimulation will be obtained using an ex vivo (human) model of precision-cut liver slices.
The ZonMW project “Use of human and animal tissue slices for the development of anti-fibrotic compounds” is focused on clinical translation, i.e., validation of precision-cut tissue slices (PCTS) ex vivo model against in vivo models, as well as on anti-inflammatory and anti-fibrotic drug development with our industrial partner, Boehringer Ingelheim. By using animal and human PCTS, we contribute to the reduction and replacement of the number of animals used in the drug development process, thereby resulting in substantial contribution to the 3Rs. Furthermore, the current project promises to explore the mechanisms of fibrosis reversal and progression that might lead to the novel targets for anti-fibrotic drugs in human disease.
Liver fibrosis is characterized by the excessive production of extracellular matrix (ECM) by myofibroblasts. A potent antifibrotic cytokine is interferon gamma (IFNg), but its clinical application is limited. Therefore, we designed a compound that contains the IFNg signaling peptide, which is selectively delivered to the platelet derived growth factor b receptor (PDGFbR) that is highly expressed on myofibroblasts. The focus of my PhD project is on the mechanism of action of this PDGFb-directed interferon gamma construct. In addition, Naomi Teekamp and I are working on the application of several of these PDGFb-receptor targeted constructs in sustained release formulations, which could be applied in fibrotic diseases.
