R35CA253119
Project Grant
Overview
Grant Description
The Role and Mechanism of Alternative RNA Splice Variants and Gene Fusions as Drivers of Cancer - Abstract
My lab has been the leader in the field of mouse modeling for brain tumors over the past 15 years. We have developed a suite of genetically engineered mouse models that are demonstrably representative of human gliomas and other tumor types. These models have been used to inform treatment options for clinical agents, and this now enables us to propose these models are suitable testbeds for testing potential major improvements to how these diseases are treated.
We have three projects:
1) We are understanding the central role of specific splice variants of TRKB in embryonic development and oncogenesis throughout the body. The RCAS modeling system has been used here to show that forced expression of the embryonic splice variant in adult tissues leads to cancer formation broadly. In this project, we will investigate the mechanisms of oncogenesis for this splice variant and determine if it could be a good diagnostic or therapeutic target.
2) We are now using the modeling system developed for glioma to address the biology of rare tumors driven by gene fusions. In this grant, we propose to understand the mechanisms of oncogenesis for YAP1 gene fusions in the rare tumors ependymoma, porocarcinoma, and aggressive meningioma (all for which we have YAP1 gene fusion-driven models currently).
3) And, we will use these mouse models to study therapeutic response and identify therapeutic strategies for these fusion-driven tumors, including identification of FDA-approved drugs that would intervene downstream of the action of the gene fusion.
My lab has been the leader in the field of mouse modeling for brain tumors over the past 15 years. We have developed a suite of genetically engineered mouse models that are demonstrably representative of human gliomas and other tumor types. These models have been used to inform treatment options for clinical agents, and this now enables us to propose these models are suitable testbeds for testing potential major improvements to how these diseases are treated.
We have three projects:
1) We are understanding the central role of specific splice variants of TRKB in embryonic development and oncogenesis throughout the body. The RCAS modeling system has been used here to show that forced expression of the embryonic splice variant in adult tissues leads to cancer formation broadly. In this project, we will investigate the mechanisms of oncogenesis for this splice variant and determine if it could be a good diagnostic or therapeutic target.
2) We are now using the modeling system developed for glioma to address the biology of rare tumors driven by gene fusions. In this grant, we propose to understand the mechanisms of oncogenesis for YAP1 gene fusions in the rare tumors ependymoma, porocarcinoma, and aggressive meningioma (all for which we have YAP1 gene fusion-driven models currently).
3) And, we will use these mouse models to study therapeutic response and identify therapeutic strategies for these fusion-driven tumors, including identification of FDA-approved drugs that would intervene downstream of the action of the gene fusion.
Awardee
Funding Goals
TO PROVIDE FUNDAMENTAL INFORMATION ON THE CAUSE AND NATURE OF CANCER IN PEOPLE, WITH THE EXPECTATION THAT THIS WILL RESULT IN BETTER METHODS OF PREVENTION, DETECTION AND DIAGNOSIS, AND TREATMENT OF NEOPLASTIC DISEASES. CANCER BIOLOGY RESEARCH INCLUDES THE FOLLOWING RESEARCH PROGRAMS: CANCER CELL BIOLOGY, CANCER IMMUNOLOGY, HEMATOLOGY AND ETIOLOGY, DNA AND CHROMOSOMAL ABERRATIONS, TUMOR BIOLOGY AND METASTASIS, AND STRUCTURAL BIOLOGY AND MOLECULAR APPLICATIONS.
Grant Program (CFDA)
Awarding / Funding Agency
Place of Performance
Washington
United States
Geographic Scope
State-Wide
Related Opportunity
Analysis Notes
Amendment Since initial award the total obligations have increased 416% from $1,056,000 to $5,450,329.
Fred Hutchinson Cancer Center was awarded
Alternative RNA Splice Variants & Gene Fusions in Cancer
Project Grant R35CA253119
worth $5,450,329
from National Cancer Institute in September 2021 with work to be completed primarily in Washington United States.
The grant
has a duration of 7 years and
was awarded through assistance program 93.396 Cancer Biology Research.
The Project Grant was awarded through grant opportunity NCI Outstanding Investigator Award (R35 Clinical Trial Not Allowed).
Status
(Ongoing)
Last Modified 8/20/25
Period of Performance
9/21/21
Start Date
8/31/28
End Date
Funding Split
$5.5M
Federal Obligation
$0.0
Non-Federal Obligation
$5.5M
Total Obligated
Activity Timeline
Transaction History
Modifications to R35CA253119
Additional Detail
Award ID FAIN
R35CA253119
SAI Number
R35CA253119-3944785985
Award ID URI
SAI UNAVAILABLE
Awardee Classifications
Nonprofit With 501(c)(3) IRS Status (Other Than An Institution Of Higher Education)
Awarding Office
75NC00 NIH National Cancer Institute
Funding Office
75NC00 NIH National Cancer Institute
Awardee UEI
TJFZLPP6NYL6
Awardee CAGE
50WB4
Performance District
WA-90
Senators
Maria Cantwell
Patty Murray
Patty Murray
Budget Funding
| Federal Account | Budget Subfunction | Object Class | Total | Percentage |
|---|---|---|---|---|
| National Cancer Institute, National Institutes of Health, Health and Human Services (075-0849) | Health research and training | Grants, subsidies, and contributions (41.0) | $2,063,793 | 100% |
Modified: 8/20/25