Bomi Lee, PhD

Overview

Aim: Biology

Pancreatic cancer is the 4th leading cause of cancer-related mortality in the US, representing an extremely lethal disease. Current treatment options are limited to conventional cytotoxic chemotherapy, and more effective treatment options are urgently needed. Chronic inflammatory condition is a prerequisite to all cancers, including pancreatic cancer. Chronic pancreatitis (CP) increases the risk of pancreatic cancer. However, it is unclear how chronic inflammatory conditions in the tissue microenvironment initiate and promote pancreatic cancer development. Our previous multi-omics analyses study with human CP tissues identified significantly elevated expression of chemokine ligand 20 (CCL20) and chemokine receptor 6 (CCR6), suggesting a potential pathogenic role of the axis in CP. Recently, our analysis of serum samples from acute pancreatitis (AP) and CP patients using the high dimensional proteomic analysis revealed a gradual increase in the level of CCL20 over the disease continuum from AP to CP, suggesting a correlation of CCL20 in pancreatitis disease progression. In addition, our pilot analysis of The Cancer Genome Atlas (TCGA) data from PDAC subjects revealed significantly increased CCL20/CCR6 mRNA expression levels in PDAC patients compared with healthy controls and an inverse correlation between CCL20 expression and PDAC patient survival rate, demonstrating that increased expression of the CCL20/CCR6 axis may be linked to PDAC disease progression. Based on our preliminary data, we hypothesize that the CCL20/CCR6 axis promotes a pro-inflammatory microenvironment in the pancreas that cooperates with oncogenic mutations and events to drive neoplastic transformation, PDAC development. We propose to 1) characterize CCL20/CCR6-associated tissue microenvironments in human CP and PDAC and 2) determine the role of the CCL20/CCR6 axis in PDAC development in vivo. Our proposed studies will significantly advance our knowledge of how the CCL20/CCR6 axis shapes a pro-tumor, inflammatory immune microenvironment to drive PDAC and unveil a novel, therapeutic approach for PDAC by targeting CCL20/CCR6.