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Title: Investigating the Role of SMAD4 in Serrated Colorectal Cancer Using an Inducible Organoid System

Name: Manisha Bandari

Major: Genetics

School affiliation: School of Arts and Sciences

Programs: Human Genetics Institute of New Jersey MacMillan Cancer Genetics Summer Undergraduate Research Fellowship (HGI-SURF)

Other contributors: Jillian Carrick, Katherine Haro, Kevin Tong, Michael Verzi

Abstract: Colorectal cancer (CRC) is one of the most common cancers in the United States. A small portion of CRCs progress though the more aggressive serrated tumor pathway, as opposed to the canonical “adenoma” pathway. While the SMAD4/TGFβ pathway is mutated in 57% of CRCs (Cancer Genome Atlas Network, 2012), the role of SMAD4 in the serrated pathway has not yet been established. The use of an organoid system provides the capability to re-express SMAD4 and directly test how SMAD4 re-expression impacts serrated tumors using a Doxycycline construct. My studies seek to address if re-expression of SMAD4 in tumor organoids will reduce the invasive phenotype normally seen in tumor organoids and decrease expression of genes involved in invasion. We indeed did see a reduction of the metastatic phenotype in SMAD4KO; BRAFV600E/+ tumor organoids and a downregulation in genes associated with colorectal cancer invasion.