Mads Gyrd-Hansen: Cancer and innate immunity
Ubiquitin signalling is an important part of the inflammatory response. However when inappropriately regulated e.g. as a result of hereditary or somatic gene mutations or infection by pathogens, this may result in serious pathologies, including immunodeficiency, chronic inflammation and cancer.
Q: What is the link between innate immunity and cancer?
MGH: Innate immunity is the part of our immune system that is the first line of defence against bacterial and viral infections, and it is a critical part of our well-being as humans. Without it we wouldn't be able to fend off micro-organisms. However, many of the processes that get activated during a normal immune response can also lead to cancer development if not properly controlled. In some cases it can also be utilised by cancer cells to promote their growth and spread within our body.
Q: How does inflammation influence tumour growth?
MGH: Inflammation promotes tumour growth by generating a lot of signalling chemicals in our body, which in normal instances is a response to a bacterial infection. These chemicals can also promote the growth of tumour cells so that they start proliferating faster and also promote the spread of tumour cells throughout the body to create metastasis. In fact a lot of cancers actually utilise this normal part of our innate immune system to promote their own growth. They can educate other cells to start producing these factors locally and promote the spread of the cancer.
Q: What is ubiquitin and how does it work?
MGH: Ubiquitin is a small protein that is encoded in our genome and it gets attached on to other proteins in our cells to change their function or where they are in the cell, or even the fate of these proteins. It regulates or controls many of the key processes in our cells, such as a cell's ability to divide or repair its DNA. In the immune system ubiquitin is absolutely critical to mount an immune response and create inflammation – it's a key signalling molecule similar to phosphorylation in our cells.
Q: What are the most important lines of research that have developed in the last 5 to 10 years?
MGH: Within my area of research I would say that it is our increased understanding of the ubiquitin molecule – all the different things that it does within the cell, all the different signals that it constitutes. We now understand that the modification of proteins by ubiquitin constitutes a complete code that can change the function of proteins in various ways and that it can affect very different cellular processes e.g. DNA repair, cell division and immune responses. We only now are starting to unravel this ubiquitin code and there are many questions that we still need to address in the future. The second line of research is our increased understanding of the relationship between us, as complex organisms, and bacteria, viruses and fungi that we interact with all the time throughout our lives. In fact most adults have about 3lb of bacteria in their intestinal system at any given time. These are very beneficial and keep us healthy but we also need to be able to deal with them and keep them at bay so that they don't colonise our body. This very close relationship between our microbial environment and understanding when this relationship breaks down and the effect that it has on human health is a very interesting relationship.
Q: Why does your line of research important and why should we put money in to it?
MGH: My lab mainly focuses on the fundamental principles about how signalling in the immune system works. Because we know that defects in this system can lead to very serious diseases (immune-related and also malignant/cancer-related), better understanding of how the principles of how we control our immune system and how it efficiently fends off invading bacteria but still keeps us healthy, is really critical. I strongly believe that if we are to develop new drugs in the future to better treat human diseases that we need to know the basic principles of how these processes work. Otherwise we won't know how to design drugs.
Q: How does your research fit into translational medicine within the department?
MGH: In addition to our basic research we also collaborate with clinicians in hospitals. An example is our current work with the clinicians in Freiburg, Germany who have primary care for patients who have an immune deficiency. We have then been able to bring together their genetic information about the mutations and actually understand how they affect the proteins that they are working with and how in this case it affects a certain part of the immune system. We can actually now start linking an inherited immune deficiency that affects these individuals with a very clear biological problem that they have in their cells, in their immune system. We really utilise our very detailed molecular understanding of cell biology and can link that in to what is happening in the clinic.