Our scientific expertise spans the network of metabolic pathways that control the production of nucleic acids as well as the signal transduction pathways that allow cells to adapt to replication stress and DNA damage repair
Certain cancers are characterized by high levels of DNA replication stress due to increased signaling from oncogenic cells. This phenomenon renders such cancers significantly more susceptible than normal cells to therapies that constrain nucleotide biosynthesis. However, these therapies are often ineffective because of three mechanisms:
Intrinsic mechanisms that protect the genome against replication stress and damage
The ability of cancer cells to switch their nucleotide production to alternate biosynthetic pathways
Biological controls that rapidly adjust consumption to compensate for insufficient production
Rapid cell division is necessary for productive T cell activation in select autoimmune diseases. The deoxyribonucleoside salvage pathway, for which deoxycytidine kinase (dCK) is the rate-limiting enzyme, is required to maintain adequate deoxycytidine triphosphate pools for DNA synthesis in the T lymphoid lineage during rapid cell division in development.