Identify the Molecular Effectors and Regulators of Myc-nick Function
The central hypothesis of this project is that Myc-nick regulates the function of a specific subset of cytoplasmic proteins that in turn promote cell survival and migration.
The first goal of this project is to test this hypothesis by identifying and characterizing proteins that are acetylated in a Myc-nick-dependent manner and mediate Myc-nick’s biological functions.
Because blocking Myc cleavage accelerates death of cancer cells, the second goal of this project is to identify inhibitors of Myc cleavage that function as synthetic lethal with hyper-activated Myc and test their therapeutic potential.
Elucidate the Role of Myc-nick in Cell Motility
The hypothesis of this project is that Myc-nick promotes cell motility by regulating the acetylation of cytoplasmic proteins that in turn control key components of the actin cytoskeleton such as fascin expression and Rho GTPase activity.
The first goal of this project is to characterize the cellular aspects involved in Myc-nick-induced cell motility and to dissect the pathways that regulate this process, including determining how fascin and GTPases are regulated by Myc-nick.
The second goal of this project is to identify pathways and inhibitors of the migratory behavior induced by Myc-nick.
Determine the Involvement of Myc-nick in Tumor Initiation and Progression
The hypothesis of this project is that Myc-nick promotes tumor cell survival during stress and facilitates the ability of tumor cells to escape the primary tumor site as the initial step towards a metastatic state.
The goal of this project is to characterize the presence and function of Myc-nick in colon in vivo, using human biopsy samples and mouse models, and to determine the relationship between Myc-nick activity with tumor stage, patient outcome, and response to chemotherapy.
Determine the Role of Myc Cleavage During Embryonic Development
The hypothesis of this project is that Myc cleavage is essential for embryonic development and cancer progression. We found that endogenous Myc-nick is expressed in the cytoplasm of many primary cell types and in adult mouse tissues. To study the in vivo relevance of Myc cleavage, we plan generate mouse models expressing a cleavage-resistant form of Myc.