Patel’s research is mainly concerned with how living cells repair DNA crosslinks. These lesions cause the two opposing strands of DNA to be covalently bound together. Such crosslinks are lethal to cells since they would prevent DNA from being copied (DNA replication) or for the genes it carries to be read (DNA transcription). DNA crosslinks are caused by numerous anti-cancer drugs (such as cisplatin), but they also must arise naturally since individuals carrying a genetic defect in crosslink repair suffer from the illness Fanconi anemia. This devastating inherited illness leads to congenital defects, progressive loss of blood production and an enormous lifetime risk of certain cancers.

Patel’s research on the Fanconi pathway has provided key molecular insights into how cells remove DNA crosslinks and, most recently, his lab discovered that reactive aldehydes are the likely natural agents that produce them. Aldehydes are ubiquitous metabolites, arising not only from many metabolic pathways but also when cells process alcohol. His lab showed that mammals utilize a two-tier protection mechanism to counteract aldehydes, consisting of (1) enzymatic clearance of aldehydes by aldehyde dehydrogenases and (2) the Fanconi DNA repair pathway (see Figure). Although Fanconi anemia is a very rare condition, genetic deficiency of this two-tier protection mechanism is actually very common in man: up to 500 million Asians are deficient in first tier protection due to mutations in the gene ALDH2.