Advisor(s)
David Macar and Tarek Mahfouz
Confirmation
1
Document Type
Poster
Location
ONU McIntosh Center; Activities Room
Start Date
11-4-2025 10:00 AM
End Date
11-4-2025 10:50 AM
Abstract
Due to an increased production of TNFα, IL 6, and IL-1β by Tumor Associated Macrophages, patients suffering from inflammatory bowel disease have an increased risk for tumorigenesis. Pro-inflammatory cytokines, such as IL-1β, promote chronic inflammation and cancer in diseases like hepatocellular carcinoma and lung cancer. The targeting of IL-1β has led to different therapeutic approaches, including protein neutralization and the inhibition of receptor binding. On the other hand, directly inhibiting gene transcription allows for higher effectiveness and specificity. Recent research revealed possible targets for low molecular weight inhibitors, specifically targeting protein-protein interactions that involve transcription factors, which provides a new approach for anti-inflammatory and anti-cancer treatments. Pharmacophore modeling using MAESTRO followed by docking of selected hits using VINA has revealed potential low-molecular weight inhibitors targeting an interaction between the C-terminal tail of the C/EBPβ dimer and a pocket of the DBD of SPI11/PU.1. Selected hits were tested in two types of myeloid leukemia cell lines. Results from our gene expression quantification via qRTPCR, chromatin immunoprecipitation co-occupancy studies, and co-immunoprecipitation followed by western blotting indicate that our inhibitor decreases IL1B/Il1b gene expression in LPS + inhibitor treated myeloid cells relative to controls and decreases Spi1:C/EBPβ interaction at the IL1B/Il1b promoter. Suggesting effectiveness of this SPI1:C/EBPβ inhibitor.
Recommended Citation
Messner, Katelyn, "Modulating Myeloid Gene Expression with a Novel Inhibitor of SPI1 and C/EBPβ Interaction" (2025). ONU Student Research Colloquium. 9.
https://digitalcommons.onu.edu/student_research_colloquium/2025/Posters/9
Restricted
Available to ONU community via local IP address and ONU login.
Modulating Myeloid Gene Expression with a Novel Inhibitor of SPI1 and C/EBPβ Interaction
ONU McIntosh Center; Activities Room
Due to an increased production of TNFα, IL 6, and IL-1β by Tumor Associated Macrophages, patients suffering from inflammatory bowel disease have an increased risk for tumorigenesis. Pro-inflammatory cytokines, such as IL-1β, promote chronic inflammation and cancer in diseases like hepatocellular carcinoma and lung cancer. The targeting of IL-1β has led to different therapeutic approaches, including protein neutralization and the inhibition of receptor binding. On the other hand, directly inhibiting gene transcription allows for higher effectiveness and specificity. Recent research revealed possible targets for low molecular weight inhibitors, specifically targeting protein-protein interactions that involve transcription factors, which provides a new approach for anti-inflammatory and anti-cancer treatments. Pharmacophore modeling using MAESTRO followed by docking of selected hits using VINA has revealed potential low-molecular weight inhibitors targeting an interaction between the C-terminal tail of the C/EBPβ dimer and a pocket of the DBD of SPI11/PU.1. Selected hits were tested in two types of myeloid leukemia cell lines. Results from our gene expression quantification via qRTPCR, chromatin immunoprecipitation co-occupancy studies, and co-immunoprecipitation followed by western blotting indicate that our inhibitor decreases IL1B/Il1b gene expression in LPS + inhibitor treated myeloid cells relative to controls and decreases Spi1:C/EBPβ interaction at the IL1B/Il1b promoter. Suggesting effectiveness of this SPI1:C/EBPβ inhibitor.