GRANTEE: Kian-Huat Lim, MD, PhD
Washington University in St. Louis
Research Project: Deactivating the Innate Immune Defense Mechanism of Pancreatic Cancer
Award: 2016 Laurie MacCaskill – Pancreatic Cancer Action Network – AACR Career Development Award
Award Period: July 1, 2016 – June 30, 2018
Dr. Lim earned his MD degree from National Taiwan University College of Medicine in 1999 and a PhD in molecular cancer biology from Duke University in 2006. His graduate work focused on dissecting the effector pathways downstream of oncogenic RAS, a protein alteration that is present in 95 percent of pancreatic cancer cases. This means that he studied cellular and signaling changes induced by the presence of mutant RAS within cancer cells. Dr. Lim subsequently completed residency training in internal medicine at Washington University in St. Louis, Mo., and an oncology fellowship at the National Cancer Institute in Bethesda, Md., where he studied the role of Toll-like receptor signaling in malignant lymphoma. He joined the division of oncology at Washington University in St. Louis in 2013 and initiated his scientific research in gastrointestinal malignancies, focusing specifically on pancreatic and colon cancers. Clinically, Dr. Lim treats patients with gastrointestinal malignancies, placing a particular focus on testing novel therapeutics with the hope of improving the outcome of patients with advanced-stage disease.
Kinases are types of proteins that physically alter other proteins to affect their activity and function. Often, kinases are abnormally active within cancer cells. Dr. Lim’s project focuses on a kind of kinase called interleukin-1 receptor associated kinase 4 (IRAK4).
Dr. Lim’s work to date has shown that the presence of activated IRAK4 in pancreatic cancer cells is significantly associated with a poor prognosis – meaning that patients whose tumors express activated IRAK4 have worse outcomes. Moreover, Dr. Lim and his colleagues’ studies suggest that IRAK4 is present in pancreatic cancer cells as well as cells of the complex microenvironment that surrounds and infiltrates pancreatic tumors. Specifically, he hypothesizes that activated IRAK4 serves as a defense mechanism for pancreatic cancer cells by promoting their survival, building a densely fibrotic stromal environment that impedes drug delivery to the tumor and likely helping pancreatic cancer cells evade the immune system to allow the cells’ growth and metastatic spread.
Using a mouse model that is genetically engineered to develop pancreatic cancer, Dr. Lim and his team will scrutinize the effects of the absence of IRAK4 in cells of the pancreas or cells of the pancreatic tumor microenvironment. He will also perform experiments using a drug inhibitor that potently blocks IRAK4 activity. These experiments should determine whether blocking IRAK4 could be a feasible strategy to prevent pancreatic cancer progression or make the cancer cells more susceptible to immune attack.