KJ_Patel

K J Patel

Chromosome breakage and repair in stem cells
kjp@mrc-lmb.cam.ac.uk

We study endogenous DNA damage and its impact on the function of vertebrate stem cells and the ageing process. Our recent work has shown that metabolism releases reactive aldehydes that are a potent source of such endogenous DNA damage. Mammals are protected against these genotoxic metabolites by first eliminating them through oxidising enzymes, and secondly by repairing the DNA damage they cause.




Kaplan-Meier graph showing survival of mice lacking two-tier protection against acetaldehyde (red) or formaldehyde (green) compared to allelic controls

 

This two-tier protection mechanism has a fundamental role in ensuring intact embryonic development, the renewal of blood and the function of vital metabolic organs. When the 2nd tier protection fails in humans, it causes the genetic illness Fanconi anaemia - such individuals accumulate endogenous DNA damage that causes defective development, loss of blood production and an enormous life-time risk of cancer.

Our current research aims to define the origins and identity of genotoxic metabolites, how cells remove them, the nature of the DNA damage they cause and how this damage is repaired. We are also want to understand how certain stem cells and organ systems are damaged by these sources of endogenous DNA damage, and the consequences of this to an organism.

Selected Papers

Group Members

  • Frederic Langevin
  • Michael Hodskinson
  • Juan Garaycoechea
  • Felix Dingler
  • Lucas Pontel
  • Lee Mulderrig
  • Guillermo Burgos Barragan
  • Niek Wit
  • Ashley Kamimae Lanning
  • Alex Frick
  • Daphne Huberts