Yee, AmyBogis, Ahlam Mukhtar2023-05-232023-05-232023-04-03https://hdl.handle.net/20.500.14154/68131There is a lack of clinical biomarkers and genetic models of ulcerative colitis (UC). Current clinical treatments are focused mainly on symptomatic relief through the use of anti-inflammatory therapy. There is unmet need to find clinical biomarker and therapeutic intervention targeting the etiology of the disease. The data from patients with colitis showed there is a decreased in HBP1 expression. Also, our analysis shows that 50% of HBP1-/- mice spontaneously develop moderate to severe colitis, and 25% of HBP1-/- mice develop CAC or dysplasia in conjunction with colitis. Furthermore, HBP1-/- mice are more susceptible to DSS-induced colitis and have decreased survival in compared to the wild type. We found a significant increase in the formation of organoids from HBP1-/- mice relative to WT, which suggest increased colonic stem-cell response to Wnt ligands in HBP1-/- mice. HBP1 is a negative regulator of HBP1 and our RNA seq analysis revealed activation of miR-155 gene set in the HBP1-/- colon. Most importantly, the immune component in the colon is altered by HBP1 deletion. Together, our data that HBP1-/- mouse could be used as a potential preclinical model for colitis. Given the role of HBP1 in altering the colonic resident immune cells, we thought to study the role of HBP1 in tumor microenvironment. We found loss of HBP1 helps in TNBC result metabolic reprogramming of the tumor microenvironment and Warburg like effect and increased in lactate production and consequently altered the tumor associated immune cells in tumor microenvironment into more immune suppressive environment. Both of my projects proposed immune system alteration in TNBC resulting from HBP1 dysfunction and also immune cell infiltration in the colonic epithelium of HBP1-/- mice.95en-USBreast cancerColitisHBP1Warburg effectThesis