The human non-coding genome contains a large number on long and small non-coding RNA transcripts, which regulate gene expression at various levels. The production and processing of such transcripts requires tight mechanisms of control to avoid the accumulation of aberrant transcripts to pathogenic levels. Members of the RNase III enzyme family, such as Dicer, maintain low levels of double-stranded RNA species, which otherwise engage a cellular defence mechanism termed innate immunity. Impaired dsRNA processing by Dicer mutation is also detrimental for the stability of the genome. Our research explores the links between the RNA metabolism, innate immunity and genome maintenance to understand how pathogenic RNA promotes tumorigenesis.
The adult stem cell niche in epithelial tissue homoeostasis and cancer
Adult stem cells take cues from their microenvironment (termed the ‘niche’) to control smooth transitions between proliferation and differentiation. Such signals are critical to maintain tissue homoeostasis and regenerate the tissue in response to injury. In diseases such as cancer, aberrant (stem) cells can acquire the ability to remodel their microenvironment for the progression of disease. Our research explores the bidirectional signalling between adult stem cells and their niche in epithelial tissue homoeostasis and cancer with the oral mucosa as model system. To address these aims, we use genetic lineage tracing, single-cell transcriptomics and organoid technology.
Dissecting Multiple Myeloma and its microenvironment with state-of-the-art technology
Multiple Myeloma is the most common cancer of the bone marrow (BM). Despite significant improvement in overall survival, most patients develop refractory disease and myeloma remains largely incurable. Myeloma is the paradigm of a tumor in its microenvironment. Similar to healthy plasma cells, myeloma cell survival is dependent on specific cell-cell interactions with non-malignant cells in the BM. This interplay takes place in the plasma cell survival niche, a poorly characterized micro-anatomical structure along the BM capillaries. In this niche, oxygen supply and nutrients are restricted, which creates a unique metabolic environment. Our group explores this multicellular ecosystem using state of the art technology with the aim to develop novel treatments for myeloma.
Stromal reprogramming of tumour draining lymph nodes in metastatic dissemination and tumour immune evasion
Metastatic disease and tumour immune evasion are two major hurdles in cancer therapy. Tumour-draining lymph nodes (TDLNs) are immunological hubs and often the first site where metastatic tumour cells are detected. We are interested in the cells of the metastatic TDLN niche, the so called stroma, and how these influence metastatic spread and anti-tumour immune responses. A main goal is to characterize the cellular cross-talk between tumour cells, cells of the immune system and the LN stroma. To do so we use an interdisciplinary approach by combining complex in vitro models, mouse models and patient samples with single-cell profiling techniques, metabolomics and proteomics.