[R01] Modeling and Characterizing the Genomic Consequences of MED12 Mutations in Uterine Fibroids
Ente: Eunice Kennedy Shriver National Institute of Child Health and Human Development
Scadenza: 2030-05-31
Importo max: 678.013 EUR
Paese: US
Descrizione
ABSTRACT
Uterine fibroids (leiomyomas) are the most widely observed tumors in women. By age 50, more than ~70% of
white and more than 80% of black women develop at least one UF tumor. Although non-malignant, they disrupt
normal uterine function and cause severe health problems ~25% of reproductive-age women. The most common
subtype, representing ~70% of all fibroids, is caused by recurrent somatic mutations in the MED12 gene that
encodes the mediator of transcription subunit 12 (MED12) protein. The lack of proper model systems hampered
our mechanistic understanding of UF development and identifying effective treatment strategies. Our long-term
goal is to interrogate the functional role of driver genetic mutations in fibroid tumors and identify potential
targetable mechanisms downstream of these mutations. Our objective in this proposal, a critical step toward our
long-term goal, is to create and exploit disease-relevant human cellular models of UF by CRISPR engineering
specific MED12 mutations, decipher their functional role in driving UF tumorigenesis and identify druggable
mechanisms to target mutant cells selectively.
Istituzione: NORTHWESTERN UNIVERSITY
PI: Mazhar Adli
Progetto: 5R01HD117479-02
Settori: Eunice Kennedy Shriver National Institute of Child Health and Human Development
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