HKDC1 and its role in intestinal inflammation and carcinogenesis

Background and current state of research
Hexokinases catalyze the first and pace-making reaction of glycolysis. HKDC1 is a novel “fifth” hexokinase isoform (Ludvik et al. 2016 Endocrinology) and strongly expressed in the epithelium of the intestinal tract (Sommer et al. 2015 Genome Biology). HKDC1 expression is dysregulated in chronic inflammatory disease (Häsler et al. 2012 Genome Research) and modulated by the intestinal microbiota (Sommer et al. 2015 Genome Biology). As HKDC1 expression is highly specific for intestinal epithelial cells and microbial effects as well as metabolic changes are tightly linked to the pathogenesis of inflammatory bowel disease or colorectal cancer, HKDC1 comes into our focus as a factor that possibly modulates susceptibility for inflammatory bowel disease and cancer in a microbiota-dependent manner.

Our goals
Our goal is to understand the interactions between the intestinal microbiome and HKDC1 along with its role for disease susceptibility. Simultaneously, we aim to identify microbial factors that regulate HKDC1 expression as candidates for microbiome-targeted disease therapies.

How to get there
We will investigate the phenotype and disease susceptibility of mice lacking HKDC1 in the intestinal epithelium. Additionally, we will screen for microbial factors regulating HKDC1 expression using in vitro assays.

References
Häsler et al. „A functional methylome map of ulcerative colitis”. Genome Research. 2012 Nov;22(11):2130-7. doi: 10.1101/gr.138347.112.
Ludvik et al. „HKDC1 is a novel hexokinase involved in whole body glucose utilization”. Endocrinology. 2016 Sep;157(9):3452-61. doi: 10.1210/en.2016-1288.
Sommer et al. „Site-specific Programming of the Host Epithelial Transcriptome by the Gut Microbiota”. Genome Biology. 2015 Mar 28;16:62. doi: 10.1186/s13059-015-0614-4.