Assistant Professor, Department of Molecular Biology and Biochemistry
University of California, Irvine (UCI)
Defining UHRF1 as a Key Factor in Pancreatic Cancer Development and Treatment
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Overview
Aim: Tumor Biology
Even though pancreatic ductal adenocarcinoma (PDAC) is now the 3rd leading cause of cancer-related death in the United States, it has a relatively low incidence and the lifetime risk of developing PDAC is less than 5%. Given that ~90% of PDACs harbor a mutation in the KRAS oncogene, KRAS mutations are widely thought to be one of the key drivers of PDAC development. It is also becoming more apparent that pancreatic lesions, called PanINs, are more common in the general population than once previously believed and most of these lesions contain mutant KRAS protein. However, most of these lesions will not develop into PDAC despite the presence of mutant KRAS. This highlights that additional genetic events are required to promote progression of these lesions into pancreatic cancer and that more research is needed to identify the key factors, along with KRAS mutations, driving PDAC development.
A Hirshberg Foundation Seed Grant Recipient for 2026, Christopher Halbrook, PhD, Assistant Professor of Molecular Biology and Biochemistry at UCI, is studying a process called epigenetic remodeling as having a key role during this early stage of PDAC development. Epigenetic remodeling refers to the changes that occur in the chromatin that controls gene expression. Preliminary data from Dr. Halbrook’s lab has demonstrated a role for a protein involved in this process, UHRF1, in the initiation and progress of PDAC in preclinical tumor models. Dr. Halbrook’s project, Defining UHRF1 as a Key Factor in Pancreatic Cancer Development and Treatment, will evaluate how UHRF1 cooperates with mutant KRAS signaling to promote tumor development using preclinical models and patient-derived organoids. Deletion of UHRF1 in these models will allow the group to evaluate how loss affects progression of PanINs to PDAC tumors, PDAC tumor growth, and PDAC tumor response to therapy. This project will define UHRF1’s role in PDAC initiation and progression and potentially identify novel therapeutic targets for pancreatic cancer patients.
The Hirshberg Foundation is excited to support Dr. Halbrook’s research into UHRF1 and defining the earliest steps of PDAC development with a 2026 Hirshberg Foundation Seed Grant Award.
