Our aim is to reveal the context-dependent mechanisms behind fibrovascular tissue growth in proliferative diabetic retinopathy (PDR) and oncogenic tissue microenvironment communication in ovarian cancer, by studying cell-cell and cell-extracellular matrix (ECM) communication in different three-dimensional in vitro and ex vivo models, as well as using omics and clinical data.
Our research aims at a deeper understanding of PDR pathogenesis, essential for devising new therapeutic strategies. PDR is a major fibrovascular complication of diabetes and a leading cause of blindness in working-age adults. It is the end-stage form of diabetic retinopathy, a multifactorial disease involving the complex interplay of microvascular, neurodegenerative, metabolic, genetic/epigenetic, immunological, and inflammation-related factors. PDR is characterized by ischemia- and inflammation-induced neovascularization, coupled with fibrotic responses at the vitreoretinal interface, which in untreated conditions lead to blindness due to vitreous hemorrhage, retinal fibrosis, tractional retinal detachment, and neovascular glaucoma. PDR pathogenesis also involves injury of neurons and glial cells, dysfunction of endothelial progenitor cells and accumulation of inflammatory cells.
Increasing evidence indicates that treatment responses are tightly connected to the ECM composition as well as the spatial arrangement and interaction between the cellular and acellular microenvironment. With this in mind, we set out to develop novel three-dimensional models to optimally recapitulate the features of human PDR pathogenesis. We utilize these models for a deeper understanding of the fibrovascular growth and remodelling mechanisms involved in PDR, as well as to test the potential of novel therapies.
In cancer research, our main focus is in ovarian cancer, aiming to understand the functions of key receptor tyrosine kinases in cell-cell communication and crucial components in cell-ECM interactions driving cancer alterations and transcriptional programs, contributing to tumor progression and treatment resistance. To reliably identify the essential mechanisms behind these processes, we have established and utilize relevant 3D cell and tissue models mimicking the different aspects of metastatic ovarian cancer microenvironment.