HKDC1 and its role in intestinal inflammation and carcinogenesis

Doctoral Researcher

Principal Investigator

Associated Principal Investigator

Background and current state of research

Hexokinases catalyse the first and pace-making reaction of glycolysis.  HKDC1 is a novel “fifth” hexokinase isoform and strongly expressed in the epithelium of the intestinal tract1. HKDC1 expression is dysregulated in chronic inflammatory disease2 and modulated by the intestinal microbiota3.

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 and 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.

 

1Sommer et al. „Site-specific Programming of the Host Epithelial Transcriptome by the Gut Microbiota” Genome Biology, published online, March 30, 2015 and Ludvik et al. HKDC1 is a novel hexokinase involved in whole body glucose utilization” Endocrinology, published online, July 30, 2016

2Häsler et al. „A functional methylome map of ulcerative colitis” Genom Research, published online, July 23, 2012

3Sommer et al. „Site-specific Programming of the Host Epithelial Transcriptome by the Gut Microbiota” Genome Biology, published online, March 30, 2015

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.