The rewiring of transcriptional networks following oncogenic mutations is a poorly understood phenomenon. By integrating the two most commonly deregulated signaling pathways found in colon cancer, I have created mouse models to study the transcriptional programs that initiate and promote oncogenesis. The goal of the proposed project is to understand transcriptional regulation of tumor initiation and progression in vivo. The project is based on the hypothesis that the transcriptional program that regulate cellular plasticity drive and the maintain oncogenesis in vivo. Results from the proposed project will greatly impact the efforts to understand the mechanism of cellular plasticity that drive and maintain oncogenic plasticity. The proposal seeks to address two specific aims: 1) Determine the transcriptional program that regulates cellular plasticity in an inducible Smad4 knockout-?-catenin gain of function mutant mouse model, and 2) Determine the extent to which Smad4 functions as a gatekeeper of Wnt signaling, which drive tumor progression. The proposal will reveal the molecular function of Smad4 in suppressing cellular plasticity, thus enabling better understanding of oncogenesis and elucidate the transcriptional mechanism regulating colon tumor progression. The project is innovative in employing inducible mouse models to study cellular plasticity and tumor progression. It relies on the notion that ?Stemness? whether it is inherent, or is acquired by the cell drive oncogenesis. Results from the project will impact our understandings on cellular plasticity that drive oncogenesis, and inform decisions on devising therapeutic strategies.

Public Health Relevance

Cellular determinants of oncogenic plasticity remain largely unknown. The proposed work is based on using in vivo mouse models to study cellular plasticity that initiate oncogenesis, and drive tumor progression. Results from the proposed work will inform decisions on devising strategies for therapeutic interventions.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Career Transition Award (K22)
Project #
5K22CA218462-03
Application #
9996519
Study Section
Subcommittee I - Transistion to Independence (NCI)
Program Officer
Jakowlew, Sonia B
Project Start
2018-09-14
Project End
2021-08-31
Budget Start
2020-09-01
Budget End
2021-08-31
Support Year
3
Fiscal Year
2020
Total Cost
Indirect Cost
Name
Stevens Institute of Technology
Department
Chemistry
Type
Biomed Engr/Col Engr/Engr Sta
DUNS #
064271570
City
Hoboken
State
NJ
Country
United States
Zip Code
07030