The cellular biology group conducts cutting-edge biological research to understand how human health is affected by factors external to the body, such as radiation, chemicals and viruses, as well as to understand how health deterioration also occurs independently of external influences.
Motivation of the groups activities and interest is based on the fact that preservation of health, which is much preferred and effective than cures for ailments, is best achieved through in-depth understanding of cellular and molecular mechanisms necessary for maintenance of healthy cells and tissues.
Towards this end, the Cellular Biology Group carries out research in, but not limited to, the following major areas: Epigenetic Ageing, Non-mutational Biological Effects of X-rays and Gamma Rays, Potential Health Benefits and Detriments of Sunlight and Ultraviolet Radiation
Almost all ill-health is caused by diseases that are associated with old age. There is increasing realisation that in wealthy societies, age-associated chronic diseases are fast becoming the greatest health burden. While ageing is inevitable, healthy ageing is achievable. To this end, the Cellular Biology group is actively investigating the mechanisms of epigenetic ageing, which is a form of ageing that is not caused by wear-and-tear of the body or accumulation of senescent cells, but is an innate process that occurs from birth. It was observed that many diseases and disorders are associated with the increased rate by which this process of epigenetic ageing occurs and vice versa. Our research is aimed at elucidating how this natural ageing occurs and what determines its rate. While the aim is not to put more years in our lives, it is aimed at putting more life in our years.
Much is already known about how radiation such as X-rays change DNA and contribute to the formation of cancer. Less known however, are the effects of radiation that do not involve changing the cell's DNA. This is the focus of the Cellular Biology Group which studies how radiation causes non-cancer diseases such as cardiovascular disease. We have uncovered radiation's ability to (i) change the chemical composition of DNA without altering its sequence, (ii) change the way by which DNA is packaged in the cell and (iii) change the level of calcium in the cell. These cause cells of the inner lining of blood vessels to become sticky and porous, allowing white blood cells and cholesterol to embed in the vessel wall, which is the first step in forming atherosclerotic plaques. We continue to elucidate other effects of radiation and how they impact on the behaviour of cells and how these may be detrimental to health.
Another type of radiation that we receive from nature is that which comes from the sun; in particular, ultraviolet radiation. While dangers of over-exposure are at the forefront of health protection advice in regards to sunlight, there are potential health benefits of sunlight that have yet to be understood. Our research confirmed that ultraviolet A (UVA) radiation triggers skin cells to produce nitric oxide, which is the most powerful blood vessel-relaxing compound known to date. This raises the possibility that controlled sunlight exposure may reduce blood pressure, which becomes elevated when blood vessels are constricted. The potential use of light therapy during winter months when sunlight is in short supply is an interesting prospect which requires further safety, efficacy and optimal conditions testing and research, which the Cellular Biology group is currently undertaking.
National Institute for Health Research, Health Protection Research Unit:
We are continuously seeking potential collaborations with all research establishments (universities, institutes and government organisations) to study the effects of environmental agents on brain functions, epigenetics, and behaviour.
Contact us if you would like to find out more detail or stay informed about a particular field of research. We are always interested in collaborating and are open to partnerships, to drive forward innovation for the benefit of the public.
Horvath S, Lu AT, Cohen H and Raj K Rapamycin retards epigenetic ageing in keratinocytes independently of its effect on cellular senescence, proliferation and differentiation. Aging (2019) May 26; 11(10) p3238-49. doi: 10.18632/aging.101976.
Lu AT, Quach A, Wilson JG, Reiner AP, Aviv A, Raj K, Hou L, Baccarelli AA, Li Y, Stewart JD, Whitsel EA, Assimes TL, Ferrucci L, Horvath S. DNA methylation GrimAge strongly predicts lifespan and healthspan. Aging (2019) Jan 21;11(2):303-327. doi: 10.18632/aging.101684
Kabacik S, Horvath S, Cohen H, Raj K. Epigenetic ageing is distinct from senescence-mediated ageing and is not prevented by telomerase expression. Aging (2018) Oct 17;10(10):2800-2815. doi: 10.18632/aging.101588.
Horvath S, Oshima J, Martin GM, Lu AT, Quach A, Cohen H, Felton S, Matsuyama M, Lowe D, Kabacik S, Wilson JG, Reiner AP, Maierhofer A, Flunkert J, Aviv A, Hou L, Baccarelli AA, Li Y, Stewart JD, Whitsel EA, Ferrucci L, Matsuyama S, Raj K. Epigenetic clock for skin and blood cells applied to Hutchinson Gilford Progeria Syndrome and ex vivo studies. Aging (2018) Jul 26;10(7):1758-1775. doi: 10.18632/aging.101508
Horvath and Raj DNA methylation-based biomarkers and the epigenetic clock theory of ageing Nature Reviews Genetics (2018) Jun;19(6):371-384.
Lu AT, GWAS of epigenetic aging rates in blood reveals a critical role for TERT. Nature Commun. 2018; 9: 387.
Raj K, The Epigenetic clock and ageing. Epigenetics of Ageing and Longevity. Translational Epigenetics Vol4: 1st Ed. (2017)
Holliman G, Lowe D, Cohen H, Felton S and Raj K. Ultraviolet Radiation-Induced Production of Nitric Oxide:A multi-cell and multi-donor analysis Sci Rep. 2017 Sep 11;7(1):11105. doi: 10.1038/s41598-017-11567-5
Sylwia Kabacik and Ken Raj Ionising radiation increases permeability of endothelium through ADAM10-mediated cleavage of VE-cadherin: Oncotarget 2017 https://doi.org/10.18632/oncotarget.18282
Philipp J, Azimzadeh O, Subramanian V, Merl-Pham J, Lowe D, Hladik D, Erbeldinger N, Ktitareva S, Fournier C, Atkinson MJ, Raj K, Tapio S. Radiation-Induced Endothelial Inflammation Is Transferred via the Secretome to Recipient Cells in a STAT-Mediated Process: J Proteome Res. 2017 Sep 14. doi: 10.1021/acs.jproteome.7b00536.
Azimzadeh O, Subramanian V, Ständer S, Merl-Pham J, Lowe D, Barjaktarovic Z, Moertl S, Raj K, Atkinson MJ, Tapio S. Proteome analysis of irradiated endothelial cells reveals persistent alteration in protein degradation and the RhoGDI and NO signalling pathways: Int J Radiat Biol. 2017 Sep;93(9):920-928.
Baselet B, Belmans N, Coninx E, Lowe D, Janssen A, Michaux A, Tabury K, Raj K, Quintens R, Benotmane MA, Baatout S, Sonveaux P, Aerts A Functional Gene Analysis Reveals Cell Cycle Changes and Inflammation in Endothelial Cells Irradiated with a Single X-ray Dose. Front Pharmacol. 2017 Apr 25;8:213.
Baselet B, Belmans N, Azimzadeh O, Erbeldinger N, Bakshi MV, Dettmering T, Lowe D, Janssen A, Michaux A, , Raj K, , Benotmane MA, Baatout S, Sonveaux P, Aerts, Soile Tapio and Quintens R Differential impact of single-dose Fe ion and X-ray irradiation on endothelial cell transcriptomic and proteomic responses Front Pharmacol. 2017 Sept 25 doi:10.3389/phar2017.00570.
Donna Lowe, Steve Horvath and Kenneth Raj Epigenetic clock analyses of cellular senescence and ageing: Oncotarget (2016) 7(8): 8524-31