Recent and ongoing research projects:
Advanced age is the main risk factor for most chronic diseases in humans, but the basic machinery that drives ageing remains largely unknown. With the exception of pluripotent embryonic stem cells, primary cells in vitro and in vivo gradually lose the ability to divide. One of the key effectors of this process is p16, a master regulator of the cell cycle whose expression results in cellular senescence. The gradual accumulation of p16 expression during physiological ageing and several ageing-associated diseases promotes p16 as a robust biomarker of human ageing. Its locus, the INK/ARF locus, is intimately involved in the susceptibility to a broad range of ageing-associated diseases, including coronary artery disease and type 2 diabetes. Targeting cellular senescence represents an exciting strategy for promoting healthy ageing.
The regulated cell proliferation that is essential for human longevity contrasts with the uncontrolled growth of cancer cells. During early tumourigenesis, cells harbouring precancerous lesions often respond by activating tumour suppressors, such as p16, and entering a premature cell cycle arrest called oncogene-induced senescence. The establishment of this growth arrest relies on the timely activation of p16, a virtual hallmark of early stage neoplasia, and acts as a vital barrier to cancer progression. By illuminating the fundamental mechanisms that regulate senescence programmes we will further our understanding of how cells sense early carcinogenic events, and the interplay between cancer progression, healthy ageing and cellular rejuvenation.
Cellular senescence, oncogene-induced senescence, cancer, ageing, cellular rejuvenation,pro-senescence therapy for cancer, p16, INK/ARF, miRNAs, exosomes.