The liver is responsible for various tasks aimed at maintaining bodily homeostasis (energy metabolism, systemic iron homeostasis, hormone production, bile metabolism etc.)
Many of these functions are regulated by dynamic regulation of hepatic gene expression
We study how liver cells regulate gene expression, thereby responding to extracellular signals and perform hepatic functions to maintain homeostasis.
Most mammals encounter frequent and prolonged bouts of fasting. Intricate mechanisms evolved to maintain homeostasis during fasting. The liver plays a central role in the response to fasting by producing fuels to supply the energetic needs of the body. Hepatocytes produce glucose and ketone bodies that are secreted to circulation to supply extra-hepatic tissues during fasting. Our lab investigates how chromatin and transcription factors regulate the fasting response.
Using genomic, metabolic and molecular biology approaches, we study the gene regulatory networks that mediate the liver’s response to fasting. We aim to better understand these transcriptional networks and how their dysregulation can contribute to obesity, diabetes and non alcoholic fatty liver disease (NAFLD).
From Korenfeld et al., 2021 Cell Mol Gastroenterol Hepatol (CMGH). PMID: 33957303
Refeeding following fasting
The re-introduction of food after a fasting period is characterized by a complex transcriptional response driving hepatic synthesis of fatty acids, triglycerides and cholesterol. We study the crosstalk between transcription factors, chromatin dynamics and enhancer activity in the refeeding phase.
Iron is an essential mineral to various physiological processes (oxygen transport, host defense etc.). Plasma iron levels are tightly regulated by secreted hepatic proteins. Both iron overload and iron deficiency have detrimental outcomes. Iron overload can lead to cirrhosis, diabetes and hepatocellular carcinoma. Iron deficiency may cause immune dysfunction and neurocognitive damage. Evidence show that iron levels are regulated by altering hepatic gene transcription. However, the scope of transcriptional regulation on iron homeostasis and its importance are largely unknown.
We adopt an unbiased approach to explore hepatic gene and chromatin regulation as mediators of iron homeostasis maintenance.
Transcription Factor Cooperation
The liver is constantly bombarded by endocrine, cytokine, metabolite and neuronal signals; many of which affect gene expression. Still, the healthy liver is able to produce a coherent response to these signals and maintain homeostasis. Cooperation between transcription factors at the chromatin template is an efficient way to integrate and converge different signals and to produce a relevant context-dependent outcome. There are various mechanisms of transcription factor cooperation and such cooperation is a prevalent mechanism to integrate extracellular and intrinsic signals in liver cells. We study mechanisms of transcription factor cooperation in regulating hepatic functions.
From Goldberg et al., 2022 Nucleic Acids Res. PMID: 35556130