"Toasting" our genomes: how alcohol and aldehydes cause us damage

A two tier protection system consisting of the enzyme  that removes acetaldehyde-Aldh2 or Adh5 that removes formaldehyde in combination with DNA crosslink repair pathway are essential for the production of blood in mice and humans. Without this protection these endogenous as well as well alcohol derived aldehydes produced through metabolism damage blood stem cells causing their loss.

In my talk I will review our research where we discovered this two tier protection system. I shall present some new data that show that the loss of these stem cells occurs through a p53 dependent mechanism. Using single stem cell reconstituted mice I describe how we can uncover the genomic sequence of two tier deficient stem cells damaged by aldehydes. I will reveal the mutational landscape that aldehydes cause in blood stem cells, and discuss how this may lead to their dysfunction and death.

Bio: KJ Patel is working on the molecular basis of inherited genomic instability and the role it plays in the biology of stem cells. His research has led to new insights into how toxins released from metabolism can damage the DNA of stem cells, particularly in those that produce blood. Studies carried out by his laboratory have uncovered how the body defends itself against these toxic metabolites through a dual protection mechanism that involves degradation of these metabolites and a specific form of DNA repair, the Fanconi anaemia DNA repair pathway. His work has also shown how the toxic by-product of alcohol metabolism, acetaldehyde, damages DNA and may contribute to diseases associated with ethanol abuse, such as fetal alcohol syndrome and certain common cancers.

KJ Patel, who is medically qualified, has had a long career in Cambridge's Laboratory of Molecular Biology, having done his PhD with Michael Neuberger. He returned for postdoctoral training, then became a tenure track group leader (MRC Senior Clinical Fellow) and has been a tenured group leader since 2007. He was elected as a Fellow of the Royal Society in 2015.