John Maciejowski, Ph.D.

Vintner Grant funded by the 2018 V Foundation Wine Celebration in honor of Lauren Ackerman

Cancer is considered a disease of the genome because the acquisition of genomic alterations can spur disease progression by disrupting natural checks and balances on cell growth and behavior. These alterations are often a result from exposure to environmental factors, such as UV light or tobacco carcinogens. They also arise as a byproduct of normal physiological processes. One of the most common alterations detected in cancer genomes are mutations that have been linked with our endogenous APOBEC enzymes. The APOBECs normally protect against viral infection by inducing mutations in viral genomes. It is not clear why this potent mutagenic activity turns against our own genomes in the context of cancer. We seek to understand how the anti-viral APOBECs become activated to attack our own genomes and to determine how this activation leads to mutation and cancer growth. We will draw on conceptual parallels between viral infection and cancer-intrinsic processes to gain insights into the mechanisms that drive APOBEC activity in the cancer setting. Our work will set the stage for the development of therapeutic interventions to blunt or leverage this mysterious mutational process.

Location: Memorial Sloan Kettering Cancer Center - New York
Proposal: Induction and mechanism of the prevalent APOBEC-associated mutational signatures in cancer
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