Cancer is often diagnosed late and through invasive and painful procedures, yet current methods don’t capture the diversity of cancer cells within the same tumor, which leads to resistance to therapy and relapse. Here, we introduce an alternative method to diagnose cancer and predict drug resistance, simply by taking a blood sample. This can be done by finding rare circulating cancer cells in cancer patients’ blood and analyzing them to identify the metabolic barcode for different cancer types and subtypes. We will start with neuroblastoma, a cancer that mostly affects young children and is hard to diagnose at early stage.

Androgens are critically involved in disease processes including infertility and cancer. The hormones target a receptor protein to regulate physiological processes or to contribute to disease progression. Thus, the androgen receptor protein is a desired drug target. A prerequisite for drug development is to know the structure of this protein. This is a major challenge as the protein is highly dynamic and tends to aggregate. We address this challenge using an innovative single-molecule technology that enables structural analysis of single protein molecules in real-time. With this approach, we will study the hormone-free structure of androgen receptor protein for the first time. Inside cells, the aggregation-prone receptor interacts with molecular chaperones that via an unknown mechanism, control the receptor’s affinity for hormone. Using our single molecule assay, we will follow this chaperone-mediated receptor regulation in real-time. With the help of a pharmaceutical company, we will explore how the chaperone-stabilized dynamic receptor protein can be drugged.

Cancer spreads when a migrating cancerous seed (metastatic niche) seeds in a new soil (tissue), a phenomenon termed metastasis. The initial seed, or the metastatic niche, is extremely small and will only grow if its needs are satisfied in the new environment. The metastatic niche requires food to metabolise and generate energy for growth. Little is known about this critical process from a metabolic point of view. Here, we aim to develop and use new technologies to measure the metabolic status of a tiny metastatic niche!

The Ebola and Lassa recent epidemic in West Africa was a major health crisis of unprecedented magnitude and impact, causing thousands of deaths and destabilizing several countries. Ebola and Lassa are two virulent diseases with high mortality rates (50% and 20% respectively). Death occurs due to vascular integrity impairment caused by the viruses that leads to severe blood loss (known as hemorrhagic shock syndrome). How the viruses cause this process is not yet fully understood, therefore, no specific treatment exists to this date. This is due to the lack of in-vitro models, as well as sensitive detection tools. In this project, we aim to uncover the metabolic alterations to endothelial cells caused by these viruses, and by extension, aid in the efforts of formulating a more effective treatment. To achieve this, the organ-on-a-chip technology will be used to model the diseases, then, the metabolic alterations will be studied using sensitive mass spectrometry approaches and will be correlated with the extent of vascular integrity loss. The resulting novel biomarkers that will be discovered will give us a better understanding of the virus effect for early detection, as well as aid in developing a more effective and specific treatment.

In the tropics, 50 million people get infected every year with the deadly Dengue virus. 500,000 of them develop hemorrhagic shock syndrome, an often-deadly condition with no cure. With climate change, this disease will become a major global issue. We lack animal models for this disease and thus no treatment has been developed. In this proposal, we aim to develop the first organ on chip model for dengue fever and its accompanying hemorrhagic shock syndrome, which will serve as a platform for novel biomarker discovery, and more targeted treatments.