Impact of Obesity and Diabetes-induced Metabolic Stresses on Cancer Cells

A. Hyperglycemic memory in cancer cells

DM-NRG1

The levels of Neuregulin-1 in tumor tissues is significantly augmented in breast cancer patient who suffer diabetes (hyperglycemic stress).

H&E and Neuregulin-1 immunostaining for tumor tissues from non-diabetic (Left, C2 and C9) vs diabetec (Right, D9 and D13) breast cancer patient.
PNAS-FARIE

Hyperglycemia epigenetically modify the enhancer region of Neuregulin-1 gene which is a potent growth factor for tumor growth.

Identify the molecular mechanisms how hyperglycemic memory occurs in oncogenic pathways of cancer cells.

B. Interplay between metabolism and DNA damage responses

Model1
Various metabolic stresses faced upon obesity and diabetes would contribute to genomic integrity of cancer cells, ie DNA damage response, which affect cancer cell behaviors.
We’re interested in the molecular mechanisms how metabolic stresses contribute to cancer cell growth and metastasis through genetic alterations in DNA damage response machinary.
Model2

Investigate the regulatory mechanisms of DNA damage response in adipocytes and its pathophysiological roles in systemic metabolism.