Tag Archives: Dominick Burton

Dominick Burton: Cellular Senescence Research Overview

My research is focused on understanding the interaction between senescent cells and cells of the immune system, with particular emphasis on cardiovascular disease.  Senescent cells are not “old” or “aged” cells as the name confusingly suggests, but rather represent a change in cell state, much in the same way the cancer cells are not “young” cells because they can proliferate indefinitely.

The senescent state is commonly induced by persistent DNA damage within cells, consequently leading to permanent proliferative arrest.  When cells activate this senescent state, they also become immunogenic-meaning they can signal, activate, and be recognised by immune cells.  As such, it  appears that the senescent state functions to eliminate damaged cells via immunogenic cell death.

Despite the ability of the immune system to destroy senescent cells, they appear to accumulate with age.  This accumulation is thought to be due to an age-related decline in immune function leading to inefficient elimination of senescent cells.  This means that senescent cells persist in our bodies, constantly secreting proteins that try to communicate with an impaired immune system.  However, some of these secreted proteins include pro-inflammatory factors that can damage the surrounding tissues.  As such, the accumulation of senescent cells with ageing is thought to promote many age-related pro-inflammatory diseases, including cardiovascular disease.  Therefore, the ability to target and eliminate senescent cells through therapeutic strategies (similar to targeting cancer cells) has the potential to alleviate age-related disease and increase health-span- the period of healthy life.

Whilst one way of targeting senescent cells (senotherapeutics) is through the use of drugs,  another approach could involve directed elimination of senescent cells by boosting an immune response or preventing its decline.  However, very little is known about how senescent cells and immune cells interact with each other, an understanding of which would be greatly beneficial for future research focused on targeting senescent cells.

As such, part of my Marie Curie Fellowship involves investigating the mechanisms by which senescent cells and immune cells interact with each to facilitate immune clearance of senescent cells.  My initial focus is on monocytes/macrophages, but as I learn more about immunology and as new findings present themselves, I will likely investigate other immune cells types such as T-cells and Neutrophils.  I will keep you updated on my progress.

To learn more about my research subject, check out my review article HERE

Dominick Burton: Introduction

My research interests for the past twelve years have been focused on various aspects of cellular senescence, with particular emphasis on ageing and age-related disease.  I undertook my PhD at the University of Brighton (UK) where I published the first data suggesting that senescent vascular smooth muscle cells adopt a pro-calcificatory phenotype that could play a role in cardiovascular disease.  During this time I developed an interest in the possible role of the immune system in eliminating senescent cells, an area of research that is now beginning to emerge.  After my PhD I undertook a Postdoctoral position at the University of Miami (USA) to investigate the potential role of cellular senescence in prostate cancer progression following therapy.  Following this two year position I got the opportunity to move to the Weizmann Institute of Science (Israel) to not only attempt to identify potential molecular targets for specifically killing senescent cells, but also to pursue my long-term interests concerning the interaction of senescent cells with components of the immune system.

Since my scientific background is mainly focused on molecular cell biology, I wanted to expand my skill set into the field of immunology so that I would be more effective at bridging the divide between research on cellular senescence and that of immunology.  To this end, I contacted Prof Helen Griffiths at the Aston University (Birmingham, UK) to co-write a Marie Curie Fellowship grant based on various ideas I have accumulated over the years.  What made the Marie Curie Fellowship particular pertinent to myself was the emphasis on developing new skills in other research areas, immunology in my case, in addition to providing training that would enable me to become a more effective independent research leader in the future.  I was confident that if I was awarded the Marie Curie Fellowship, Aston University would be more than capable of helping me achieve my end goals.

So of course I was ecstatic when I found out earlier this year that I was awarded a Marie Curie Research Fellowship for my project entitled “The interaction and clearance of senescent vascular cells by the innate immune system” (more on this in a later blog) which I have now started as of 1st June 2015.  It is now coming up to three months at the Aston University, so what are my thoughts so far?  You will have to wait for my next blog.

Aston University profile page: http://www.aston.ac.uk/lhs/staff/az-index/dr-dominick-burton/