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Welcome to the D'Andrea Lab
The D'Andrea lab investigates chromosome instability and susceptibility to cancer. Our laboratory examines the molecular signaling pathways which regulate the DNA damage response in mammalian cells. Disruption of these pathways, by germline or somatic mutation, leads to genomic instability, cellular sensitivity to ionizing radiation, and defective cell cycle checkpoints and DNA repair. These pathways are often disrupted in cancer cells, accounting for the chromosome instability and increased mutation frequency in human tumors. Our primary focus is the molecular pathogenesis of the human chromosome instability syndromes: Fanconi anemia (FA), ataxia-telangiectasia (AT), and Bloom syndrome (BS). FA is an autosomal-recessive cancer susceptibility disorder characterized by developmental defects and increased cellular sensitivity to DNA crosslinking agents. Twenty three FA gene have been identified to date, and the encoded FA proteins cooperate in a common cellular pathway regulating DNA interstrand crosslink repair and replication fork stability. Acquired mutations in genes in this pathway account for the chromosome instability and replication fork instability of many common cancers.
Our laboratory is also interested in identifying new targets, and new small molecule inhibitors for cancers which function via the mechanism of synthetic lethality (SL). We have identified the new SL targets, Polymerase Q(POLQ) and USP1, as well as the corresponding small molecule inhibitors of their targets. Importantly, POLQi and USP1i can overcome the resistance of BRCA1/2 deficient tumors to the PARP inhibitors.
The D'Andrea lab investigates chromosome instability and susceptibility to cancer. Our laboratory examines the molecular signaling pathways which regulate the DNA damage response in mammalian cells. Disruption of these pathways, by germline or somatic mutation, leads to genomic instability, cellular sensitivity to ionizing radiation, and defective cell cycle checkpoints and DNA repair. These pathways are often disrupted in cancer cells, accounting for the chromosome instability and increased mutation frequency in human tumors. Our primary focus is the molecular pathogenesis of the human chromosome instability syndromes: Fanconi anemia (FA), ataxia-telangiectasia (AT), and Bloom syndrome (BS). FA is an autosomal-recessive cancer susceptibility disorder characterized by developmental defects and increased cellular sensitivity to DNA crosslinking agents. Twenty three FA gene have been identified to date, and the encoded FA proteins cooperate in a common cellular pathway regulating DNA interstrand crosslink repair and replication fork stability. Acquired mutations in genes in this pathway account for the chromosome instability and replication fork instability of many common cancers.
Our laboratory is also interested in identifying new targets, and new small molecule inhibitors for cancers which function via the mechanism of synthetic lethality (SL). We have identified the new SL targets, Polymerase Q(POLQ) and USP1, as well as the corresponding small molecule inhibitors of their targets. Importantly, POLQi and USP1i can overcome the resistance of BRCA1/2 deficient tumors to the PARP inhibitors.
