The lab started in 2012 with a vision to develop innovative therapeutic technologies which are translatable to clinic. Since then, the lab has been performing dynamic research in the multi-/inter-disciplinary fields of identification of novel targets in fibrotic and inflammatory microenvironment, peptide therapeutics, targeted drug delivery, nanomedicine and biology for fibrosis and cancer. In recent years, the significance of fibrosis in cancer has been highlighted in driving the tumor progression and metastasis. The crosstalk between tumor cells and stromal cells such as cancer-associated fibroblasts (CAFs) and tumor-associated macrophages (TAMs) as well as extracellular matrix (ECM) is essential to maintain and stimulate the tumor growth and progression. The lab is, on the one hand, uncovering the underlying biology of tumor stroma interaction, while on the other hand, developing innovative technologies to target specific tumor stromal cells to inhibit their pro-tumorigenic effects and thereby improve the efficacy of anti-cancer therapies. The lab has the following major research themes:
I. Identifying Novel Targets in the Tumor Microenvironment
Understanding the crosstalk between different cell types within the tumor microenvironment, especially focused on CAFs, TAMs and ECM interaction. We have identified several therapeutic targets which have been involved in these crosstalks (Kuninty et al 2016, Binnemars-Postma et al, 2018, Schnittert et al, 2018, Kuninty et al. 2019).
II. Peptide Technologies and Nanotechnologies to modulate the Tumor Microenvironment
Peptide technologies as therapeutics to re-program the tumor microenvironment in order to enhance anti-tumour effect of chemotherapy – the lab has recently developed novel integrin targeting peptides (Kuninty et al 2018, Kuninty et al. 2019) which has led to the startup company ScarTec Therapeutics BV.
Targeted nanomedicine to deliver therapeutic molecules (e.g. microRNA delivery, protein and peptide delivery) to specific cells within the tumor microenvironment to treat cancer. We have recently developed technologies to deliver anti-miRNA (Schnittert et al 2017) and peptide hormone (Mardhian et al 2018) using nanoparticles.
III. 3D technologies emulating the Tumor Microenvironment
Three-dimensional (3D) technologies to emulate the tumor microenvironment (e.g. multicellular tumor spheroids, 3D bioprinted tumor models). We have developed 3D heterospheroid tumor model and studied nanoparticle penetration (Priwitaningrum et al 2016) and recently 3D bioprinted mini-brain model (Heinrich et al, 2019).
3D culture models such as spheroids better resemble the in vivo situation compared to 2D models, and more realistically recapitulate the tumor microenvironment offering advantages of resembling in vivo tumor microenvironment, enabling thereby a better understanding of molecular and cellular mechanisms and cell-matrix interactions. Furthermore, they can facilitate better screening of nanomedicines. 3D in vitro models also yield more predictive in vitro data and support the reduction of animal studies which are costly and suffering from high failures rates; for all these reasons, 3D in vitro models are particularly attractive for screening of clinically relevant properties of nanomedicines.