Mechanistic understanding of how obesity causes cancer – Research project #3: How does physiological stressors affect somatic fully differentiated cells of the body?

Obesity increases the risk of developing thirteen types of cancer that normal weight individuals may not develop despite of harbouring the same cancer risk loci. Globally, overweight/obesity may account for 544 300 cancer cases every year and is currently implicated in 15-20% of cancer-related mortalities. This places obesity second only to smoking as the most prevalent preventable cause of cancer.

This project address two areas that we believe are currently severely understudied: 1) How does the obese phenotype affect male and female germ cells and thereby the intergenerational metabolic health and 2) How does a history of obesity affect future possibilities of cancer risk (epigenetic memory).

AIM

The aims are to:

• Uncover the relationship between systemic metabolic challenge the epigenetic landscape of both male and female germ cells.
• Demonstrate how efficiently the obese phenotype is transferred between generations in mice.
• Conduct generational cancer studies.

APPROACH

Key methodologies for this project are single cell transcriptomics and epigenomics, metabolomics, mouse in vitro fertilization and advanced mouse cancer models (genetic and viral based).