2020 Grantee: Daria Esterházy, PhD
University of Chicago
Research Project: Duodenal Control of Pancreatic Ductal Adenocarcinoma
Award: 2020 Pancreatic Cancer Action Network Career Development Award
Award Period: Sept. 1, 2020 – Aug. 31, 2022
Dr. Daria Esterházy received her BA (2005) and MSci (2006) in natural sciences from Gonville and Caius College, University of Cambridge in the United Kingdom. She obtained her PhD in 2010 with Dr. Markus Stoffel at ETH Zurich, Switzerland, studying the control of hormone-producing beta cells within the pancreas.
For her postdoctoral studies, Dr. Esterházy joined the laboratory of Drs. David Mangelsdorf and Stephen Kliewer at UT Southwestern Medical Center at Dallas in 2012, where she investigated intestinal hormones released after meals. In 2013, Dr. Esterházy moved to the laboratory of mucosal immunology of Dr. Daniel Mucida at The Rockefeller University. There she studied how immune cells called peripheral regulatory T-cells, which can prevent adverse reactions to food or gut bacteria, are generated in lymph nodes.
In 2018, Dr. Esterházy joined the University of Chicago as an assistant professor. The Esterházy lab is interested in how immune balance is kept in the digestive system and how its failure can lead to severe disorders and diseases. In particular, the lab explores how the intestine may influence the pancreatic immune system.
Pancreatic tumors are considered immunologically “cold,” which means that cancer-killing immune cells are not present in the tumor’s surrounding microenvironment, and immunotherapy approaches have been historically unsuccessful for most pancreatic cancer patients. Part of this is due to immunosuppression, which refers to cells or other factors that prevent immune activation and attack.
It is also appreciated that inflammation of the pancreas (pancreatitis) may precede pancreatic cancer (pancreatic ductal adenocarcinoma) development. However, the anatomical and environmental inflammatory origins are poorly understood.
Adaptive immunity is initiated in lymph nodes, but how pancreatic lymph nodes respond to this organ’s antigens (proteins that may be recognized by the immune system) in healthy and tumor settings – and therefore may contribute to the inappropriate balance between immunosuppression and inflammation – has not been investigated.
The pancreas has multiple unique connections to the duodenum, the uppermost part of the small intestine, a fact rarely considered in the context of pancreatic cancer. Dr. Esterházy and her colleagues thus postulate that a major origin of early inflammatory triggers in pancreatic cancer is the duodenum.
Dr. Esterházy’s Career Development Award project will focus on the role of the duodenum’s contents in pancreatic inflammation and early pancreatic cancer development as well as the power of shared lymph node drainage in shaping pancreatic immunity.
This project addresses both the initiating events and the adaptive immune failure in pancreatic cancer development through the lens of the duodenum. Understanding the consequences of intestinal changes on the pancreatic tumor environment may inform radically new treatment options that harness the unique connection of these organs.