The development of new medicines is dependent on the identification of novel drug targets. Chemical Biology combines chemistry and biology to generate small molecule called chemical probes, used to study the role of proteins as potential targets. Dr Kilian Huber uses different approaches to develop chemical probes that may provide leads for drug discovery.
In the search for new medicines for cancer or inflammatory disorders, small molecules are invaluable tools for testing the activity of possible target proteins. Those small chemical compounds can also affect the morphology and phenotype of cell samples collected from patients, opening the possibility to develop new therapeutics.
Ultimately, medical research must translate into improved treatments for patients. At the Nuffield Department of Medicine, our researchers collaborate to develop better health care, improved quality of life, and enhanced preventative measures for all patients. Our findings in the laboratory are translated into changes in clinical practice, from bench to bedside.
Q: What is your approach to helping develop new drugs?
Kilian Huber: If you want to develop a new drug, it is important that you have a good target whose activity you would want to modulate with that drug. Then of course the question is how do you come up with a good target and that is what our lab is mainly interested in. We try to develop new approaches that can help to identify new targets that are relevant for the treatment of human disease.
Q: How do you go about identifying a new drug target?
KH: We are pursuing two different strategies. In one of them, we try to develop small molecule tools: small chemical compounds that people can use to test the activity of a given protein which is most likely to be the kind of target you are looking for within a cellular system or a tissue.
In the other approach, we take patient samples or human tissue and we incubate these samples with small molecules. Then we see how the small molecules affect the morphology and the phenotype of these cells. In, most cases we will not know how these compounds work, which is why we then take them and try to understand the mode of action, using a technology that we call chemical proteomics.
Q: Are there particular diseases that you are interested in?
KH: We are very much interested in human cancers and we study a broad variety of leukaemias and solid tumours. We are also interested in inflammatory disorders such as rheumatoid arthritis and viral infections.
Q: What are the most important lines of research that have emerged in the last 5-10 years?
KH: I think nowadays people appreciate much more the complexity of human biology and thus of human disease. People understand that it is very unlikely that you will be able to make a drug that interacts only with one protein and then will cure a disease. Diseases are very complex: often it is not just one protein that is acting weirdly within the cell, it will be several of them and if you alter the activity of one of them, the other will then compensate for it. It is important to use good model systems that are representative of the disease and we try to identify the molecules that are hitting all the right nodes in that network.
Q: Why does your line of research matter and why should be fund it?
KH: Our aim is to accelerate drug discovery by providing new targets to the community. We offer our reagents and tool compounds for free: everything is open access and anyone who wants to use it can get it for free from us. We do this to enable other researchers to further investigate these new targets, and also pharmaceutical companies, so that they can start drug discovery programmes. I think considering the burden of disease like cancer and inflammatory disorders, people will appreciate that it is important to have new therapeutics to be able to treat these disorders.
Q: How does your research fit into translational medicine within the department?
KH: For us it is very important that our results are relevant for the treatment of human disease. We want to see if our molecules really work in patient tissue. We collaborate with clinicians and we ask them to provide us with samples from patients. We then treat the samples with small molecules and then see if they give an interesting phenotype. Then we give these molecules back to the clinicians so they can then study the effects in patients.