Leader: Jiha Kim
Project Title: Perivascular Remodeling to Enhance Drug Delivery in Pancreatic Cancer
Pancreatic cancer field is suffering from the lack of effective treatment options largely due to the limited deliver efficacy of the drugs. Pancreatic ductal adenocarcinoma (PDAC) presents a hostile tumor microenvironment (TME) that is stroma-rich, hypoxic, hypovascular, and with poor perfusion efficiency which can largely contribute to tumor progression/metastasis and the limited delivery efficacy of treatment drugs. Previously we have shown that perivascular landscape can be modified upon changes of TME and have a profound effect on vascular function.
Our research is focused on investigating the perivascular plasticity in the various tumor microenvironment and novel ways to re-invest them into tumor vasculature which will lead to the significantly increased vascular stability and perfusion efficacy. We will utilize both orthotopic and spontaneous mouse models of pancreatic cancer and perform comprehensive pericyte phenotyping at different stages of angiogenic remodeling by employing multispectral imaging of immunolabeled tumors. We will determine the molecular conversion mechanism that influences pericyte phenotypes using in-vitro co-culture system. Finally, we will evaluate the therapeutic efficacy of pericytes re-investment in combination with chemotherapeutic agents using mouse model systems for pancreatic cancer.
Properly structured vasculature will substantially enhance the drug delivery efficacy and provide an opportunity to repurpose previously failed cytotoxic agents. This study will contribute to our current understanding of the importance of proper perivascular investment and identify efficient combinatorial treatment for Pancreatic cancer patients.