top of page

Lab of Nutrigenomics, Liver Biology and Gene Expression

1/1

RESEARCH

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.

fasting

Fasting

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).

AA graphical abstract.jpeg

From Korenfeld et al., 2021 Cell Mol Gastroenterol Hepatol (CMGH). PMID: 33957303

refeeding

Refeeding following fasting

Goldstein Lab icon-03.png

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.

intermittent fasting

Intermittent
Fasting

Goldstein Lab icon-04.png

A multitude of studies in mammals, especially rodents and humans, examined the effects of nutritional regimens that involve recurring fasting events (i.e. intermittent fasting). Far-reaching health benefits were reported in rodents and humans experiencing intermittent fasting. These benefits include improvements in glucose tolerance, insulin sensitivity and lipid profiles as well as weight loss. Also, amelioration of obesity, diabetes, steatosis, hypertension, inflammation, certain cancers and neurodegenerative diseases were observed.

We found that mice undergoing alternate-day fasting (ADF) respond profoundly differently to a following fasting bout compared to mice first experiencing fasting. Hundreds of genes enabling ketogenesis are ‘sensitized’ (induced more strongly by fasting following ADF). Liver enhancers regulating these genes are also sensitized and harbour increased binding of PPARα, the main ketogenic transcription factor. ADF leads to augmented ketogenesis compared to a single fasting bout in wild-type, but not hepatocyte-specific PPARα-deficient mice. Thus, we found that past fasting events are ‘remembered’ in hepatocytes, sensitizing their enhancers to the next fasting bout and augment ketogenesis. Our findings shed light on transcriptional regulation mediating adaptation to repeated signals.

graphical abstract new-rectangle.png

From Korenfeld et al., 2024 Nucleic Acids Res. PMID: 39673515

transcription factor

Transcription Factor Cooperation

Goldstein Lab icon-01.png

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

tel aviv4.jpg

bottom of page