Projects
Nanobody-based approach to inhibit RAS activity by modultating its interactome KU Leuven
Our proposal represents a novel approach to block RAS activity. We will utilize the Nanobody platform to isolate high-affinity Nanobodies that facilitate or inhibit the complex of RAS with its upstream regulators. We will screen for Nanobodies that suppress the RAS pathway in melanoma cells with different mutational status of BRAF and NRAS. We will assess the mechanisme of RAS inhibition. We will next elucidate the potency of the generated ...
The role of RAS ubiquitination in cancer development and progression. KU Leuven
The RAS GTPases are among the most commonly mutated oncoproteins in human cancers. We and others recently demonstrated a crucial role of reversible ubiquitination in regulation of the RAS GTPases. The primary objective of the proposed study is to understand the contribution of RAS ubiquitination in RAS-mediated tumorigenesis. Using a quantitative proteomic analysis of the ubiquitinated RAS interactome, we will assess how ubiquitination ...
The role of PTK2B kinase in the RalA signaling pathway and cancer development. KU Leuven
The role of the actin cytoskeleton in the regulation of the Hippo pathway KU Leuven
The Hippo pathway effectors YAP (Yes-associated protein) and TAZ (Transcriptional coactivator with PDZ-binding motif) promote organ growth and tumorigenesis and are indicated as promising targets for cancer therapy. This is because they are hyperactivated with high frequency in different types of human cancer, because their knockout or knockdown suppressed tumor development and maintenance in various preclinical cancer models, and because ...
The role of LZTR1 in cancer development and progression KU Leuven
The RAS pathway is one of the most commonly activated signaling nodes in human disease. Despite more than three decades of intensive effort, the task of developing effective therapeutic strategies for RAS-driven disease remains daunting. About one-third of human cancers have somatic mutations in one of the RAS genes (HRAS, NRAS, KRAS4A, and KRAS4B). KRAS mutations are present in 20% to 25% of patient with lung cancer. Lung cancer is the ...
Identification of flow-inducible BMP signalling pathways and characterization of their role during embryonic vascular remodelling KU Leuven
The circulatory system is the first organ system to become functional during embryonic development and is required for survival of the embryo. As such, the vasculature must grow with the embryo, be efficient, and perfuse all tissues and organs. In the mouse embryonic yolk sac, the initial vasculature consists of a randomly organized, honeycomb-like network of capillaries. As the heart begins to beat and red blood cells enter circulation, this ...
Role of NRas ubiquitination in control of melanoma development and progression. KU Leuven
Melanoma is one of the most aggressive skin cancers. The 15–20% of all melanomas harbors activating NRas mutations. At present, little progress has been made in developing targeted therapy strategies for NRas mutant melanoma, thus a better understanding of the Ras pathway is an urgent need for establishing new treatment strategies. We and others have recently demonstrated that ubiquitination of the Ras family members dramatically affects ...
Unraveling the sugar metabolism of Candida albicans to find new antifungal drugs KU Leuven
Candida albicans is an opportunistic fungal pathogen which infection rate became more frequent over the last years. Another problem is their rising resistance against the available antifungal drugs on the market, like fluconazole. Therefore, C. albicans is a relevant health problem and there is an urgent need for new antifungal drugs with a complete novel mode of action to counteract the spread of this fungus. To colonize the human body this ...
Cognition and Behavior in Neurofibromatosis Type 1 and Legius Syndrome KU Leuven
Neurofibromatosis Type 1 (NF1)
is a frequent autosomal dominant genetic disorder (1/2700 newborns). It is known as a RASopathy, caused by a mutation in the NF1 gene encoding neurofibromin, which is a negative regulator of the RAS (Rat sarcoma) / MAPK (Mitogen Activated Protein Kinase) pathway. This pathway has an important role in the process of cell proliferation and differentiation. However in recent years, ...