Changyu Zhu, PhD

Hans Popper Memorial Postdoctoral Research Fellowship Award
$25,000 over one year

Sloan Kettering Institute for Cancer Research

The crosstalk between fatty liver disease and liver metastasis
Mentor: Scott W. Lowe, PhD

Nonalcoholic fatty liver disease (NAFLD) is defined by abnormal accumulation of lipids within the liver. Due to the high prevalence of obesity, it is the most common chronic liver disease worldwide and affects over 80 million people in the United States alone. As such, NAFLD is becoming an important factor that influences liver metastasis, which occurs frequently in various types of cancer including pancreatic cancer. However, the links between fatty liver and metastasis remain largely unknown.

In cancer patients, I found that the majority of patients with liver metastases exhibited liver fat accumulation. An obesogenic high-fat diet strongly promoted liver metastasis in mouse models of pancreatic cancer, a process that is mostly due to fat transfer from the fatty liver into the cancer cells. My results pinpoint the causal relationship between NAFLD and liver metastasis, and my research focuses on the molecular and cellular interactions between the two. Specifically, I will study how cancer cells trigger the release of lipids from nearby liver cells, and determine the impact of lipid uptake into metastasis on the surrounding immune cells.

These studies will improve our understanding of the vulnerabilities of liver metastasis arising in a lipid-rich environment of NAFLD. In contrast to most approaches that focus on cancer cells alone, my research will test a conceptually new type of therapeutic strategy that blocks the crosstalk between cancer cells and liver cells, with the ultimate goal of uncovering new targets to effectively treat metastasis in an increasingly common subset of cancer patients.