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HuR’s role in pancreatic cancer metastasis

Award Number: F30CA306284
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 07/16/2025
PERIOD OF PERFORMANCE END DATE: 07/15/2029

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HuR’s role in pancreatic cancer metastasis - PROJECT SUMMARY Pancreatic ductal adenocarcinoma (PDAC), the most common pancreatic cancer pathologic subtype, has a 5- year survival rate of only 13%, largely due to its metastatic propensity. Most patients present with metastatic disease, rendering them ineligible for curative intent surgery. Among those that undergo a successful resection, 78% will have metastatic recurrence within 2-years. Despite significant efforts to identify metastasis-specific driver mutations, few targetable pathways have been identified, underscoring the need to explore alternative mechanisms, such as post-transcriptional regulation. Human antigen R (HuR, ELAVL1) is an RNA-binding protein implicated in post-transcriptional regulation of stress-adaptive networks. We propose HuR is essential for PDAC cells to overcome challenges associated with the metastatic cascade. Under stress conditions, HuR stabilizes and enhances translation of mRNAs required for cellular adaptation. Preliminary data from our lab reveal that HuR knockout (KO) in PDAC cells via CRISPR-Cas9 reduces liver metastatic burden in our orthotopic murine metastatic model, highlighting HuR activity as a potential therapeutic vulnerability in metastasis. My central hypothesis is that HuR is a key regulator of PDAC metastasis by selectively stabilizing pro-metastasis mRNA targets. In Aim 1, I will investigate the functional role of HuR in supporting PDAC metastasis. I hypothesize that HuR is most critical for metastasis during the outgrowth phase in the secondary site, when PDAC cells must adapt to unique secondary site microenvironments. To test this, I will rescue HuR activity at distinct stages of metastasis in our HuR KO murine model and monitor metastatic burden. Additionally, I will assess HuR expression levels and activity in matched primary and metastatic tumors from human PDAC patients to determine whether metastatic lesions have a greater reliance on HuR. In Aim 2, I will identify HuR-bound mRNAs that mediate metastatic adaptation. I hypothesize that HuR modulates distinct mRNA targets and pathways depending on site-specific stress conditions. To test this, I will perform RNA immunoprecipitation sequencing (RIP-seq) on primary, liver, and lung metastatic PDAC tumors to comprehensively map HuR mRNA binding targets specific to metastasis biology. These targets will be prioritized using PDAC patient RNA-seq datasets and clinical data from the Brenden-Colson Center for Pancreatic Care (BCCPC) at Oregon Health and Science University (OHSU). I will validate identified HuR-bound mRNA PDAC metastatic drivers as bona fide HuR targets through various molecular techniques, such as independent RIP-qPCR, western blot analysis, and actinomycin D decay assays. Lastly, I will assess the functional relevance of top targets using target site blockers (TSBs) to disrupt HuR–mRNA target interactions and measure the effects on metastasis. Importantly, integrating preclinical and clinical data will enhance the translational impact of these findings. Completion of this proposal will elucidate a novel mechanism by which PDAC cells utilize HuR to successfully metastasize, identifying specific HuR-dependent pathways as potential therapeutic vulnerabilities in PDAC.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $55,114 )
2026	2026	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	Cancer Research Manpower	000	2	7/28/2026	NON-COMPETING CONTINUATION	$55,114
														Subtotal = $55,114

Issue Date FY: 2025 ( Subtotal = $54,538 )
2025	2025	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	Cancer Research Manpower	001	1	7/16/2025	NEW	$0
2025	2025	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	Cancer Research Manpower	000	1	7/16/2025	NEW	$54,538
														Subtotal = $54,538

Grand Total All Awards = $109,652

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HuR’s role in pancreatic cancer metastasis

Award Number: F30CA306284

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 07/16/2025

PERIOD OF PERFORMANCE END DATE: 07/15/2029

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