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 Joao Paulo  Costa Pinho

Joao Paulo Costa Pinho

Joao Paulo Costa Pinho

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Advisor : Charles Chalfant

Program

Ph.D.

My project focuses on mechanisms of tumorigenesis of non-small cell lung cancer involving caspases. Broadly speaking, caspases are a family of proteases whose most well-known role is initiation and execution of apoptosis. Caspase 9, specifically, is an initiator caspase of the intrinsic pathway (triggered by release of cytochrome c from mitochondria). In its “normal” form, it has roles in development (such as pruning of neuronal connections) and behaves as a tumor suppressor. My project investigates an isoform known as caspase 9b (C9b), produced by alternative splicing of the Casp9 gene. C9b acts as an inhibitor of C9a, promoting cell survival and proliferation, which makes it pro-oncogenic. Our group has demonstrated that this phenotype occurs due to activation of the canonical NF-?B pathway. We now aim to elucidate whether, both in vitro and in vivo, this C9b/ NF-?B system collaborates with other oncogenic drivers, such as certain K-ras mutants and MYC.