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GRANTEE: MATTHIAS HEBROK, PHD
Institution: University of California, San Francisco
Research Project: Role of miRNAs in Pancreatic Adenocarcinoma
Award: Abby Sobrato – Pancreatic Cancer Action Network – AACR Innovative Grant
Award Period: July 1, 2011 – June 30, 2013
Amount: $200,000
Click here to download Dr. Hebrok’s 2011 Grant Snapshot (pdf)
Institution: University of California, San Francisco
Research Project: NF-kB Signaling in PanIN Formation
Award: Michael C. Sandler – Pancreatic Cancer Action Network – AACR Pilot Grant
Award Period: July 1, 2008 – June 30, 2010
Amount: $100,000
Click here to download Dr. Hebrok’s 2008 Grant Snapshot (pdf)
Biographical Highlights
Prior to this award, Dr. Hebrok was also the recipient of the 2008 Michael C. Sandler – Pancreatic Cancer Action Network – AACR Pilot Grant. The Pilot Award mechanism has been renamed to Innovative Awards, providing funding to novel and creative projects focused on pancreatic cancer.
Dr. Hebrok is the Hurlbut-Johnson Distinguished Professor in Diabetes Research and Director of the UCSF Diabetes Center. He performed his PhD studies at the Max-Planck-Institute for Immunobiology in Freiburg, Germany. His postdoctoral work was completed at the Howard Hughes Medical Institute at Harvard University. Dr. Hebrok has been at UCSF since 1999. His laboratory uses cell, molecular, and developmental biology approaches to understand normal pancreatic development, as well as pancreatic diseases, including diabetes and cancer.
2011 Project Overview
General function of RNA is to serve as an intermediary between genes (DNA) and proteins. However, a recently discovered class of RNAs, called microRNA or miRNA, is made up of small sequences of nucleic acid that do not code for proteins. Instead, miRNAs positively or negatively regulate the process by which coding RNAs lead to the expression of certain proteins. In cancer, miRNAs lead to aberrant expression of proteins that affect growth, survival, and other cellular features that transform normal cells into cancer cells.
Dr. Hebrok’s work aims to better understand the role of miRNAs in pancreatic cancer initiation and progression, as well as decipher which miRNAs become activated throughout each step of the development of the disease. Additionally, there has been a great deal of recent attention to the tissue surrounding a tumor, or stroma. The stroma is thought to support and nourish the tumor, and potentially impede drug delivery. Dr. Hebrok will analyze how stroma-epithelial interactions change the expression of miRNAs in pancreatic cancer cells. Subsequently, he will manipulate miRNA levels in pancreatic cancer cells themselves. In addition, he will eliminate critical miRNAs in a mouse model of pancreatic cancer. These studies will shed light on the expression and function of miRNAs throughout the progression of pancreatic cancer, potentially leading to improved drug targets or markers to detect earlier disease.
2008 Project Overview
Pancreatic ductal adenocarcinoma (PDAC) develops through a sequence of precancerous lesions called “pancreatic intraepithelial neoplasias” or PanINs. Recently, mouse models of PDAC have been created that recapitulate (repeat in its development) human PanIN progression. However, because lesion formation in these mice occurs gradually and the onset of specific stages is variable, the molecular requirements for the different stages have been difficult to interpret. A rapid and synchronized mouse model of PDAC precancerous lesions has been developed using chemical induction of pancreatitis (inflammation of the pancreas), which is frequently correlated with PDAC in humans. The use of this model allows the role of specific pathways to be efficiently determined in the earliest disease stages. Preliminary data using this model show that NF-kB signaling, a pathway that is involved in inflammation and cell proliferation and is highly active in human pancreatitis and PDAC, plays a significant role in lesion formation.
The funded project involves genetic experiments that explore the role of NF-kB signaling in the progression of healthy pancreatic epithelium (the cellular covering of the pancreas) to pre-cancerous lesions. This study aims to better understand the mechanisms by which this pathway guides the progression from normal pancreatic cells to PanINs. Plans are to characterize the effects of disrupting NF-kB signaling in PanIN progression and to determine which cells, in the transition from normal to disease state, possess active NF-kB signaling. Results are expected to provide the field with important indications of the therapeutic and diagnostic possibilities involving the NF-kB pathway.
