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tRNA modification reprogramming and translational remodeling in cancer

Award Number: U01CA305187
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: COOPERATIVE AGREEMENT
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/28/2025
PERIOD OF PERFORMANCE END DATE: 07/31/2030

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tRNA modification reprogramming and translational remodeling in cancer - Project summary Over 300 different chemical modifications on RNA have been identified and this ‘epitranscriptome’ plays important roles in the posttranscriptional control of gene expression. Dysregulation of certain RNA-modifying enzymes including RNA methyltransferases (MTases) is linked to cancer initiation and progression, and new evidence suggests these may provide a new class of druggable targets for treating various cancer types. Transfer RNA (tRNA) functions in deciphering the genetic code in mRNAs via codon-anticodon interactions and is one of the most heavily modified RNA species in cells. The diverse and numerous chemical modifications of the anticodon and main body of tRNAs are critical for tRNA integrity and function, thereby affecting protein synthesis. This project will provide major new insight into the role of tRNA modification reprograming and translational remodeling in cancer and cellular stress responses. RNA mass spectrometry and sequencing approaches will be used to comprehensively catalogue tRNA modification and expression dynamics during melanoma progression and metastasis using both human patient-derived xenografts and clinical samples. An innovative new methodology for enhanced Ribosome profiling will be deployed to correlate RNA modification changes with cancer-associated translational remodeling at codon resolution. Functional screening of all >600 human tRNA genes will be performed to identify individual tRNA genes involved in various stress response pathways in cancer cells, as well as tumorigenesis and metastasis in vivo. The role of several tRNA-modifying enzymes and individual tRNAs in melanoma progression and stress response pathways will be investigated, and RNA mass spectrometry, tRNA sequencing, Ribo-seq, and proteomic studies will be used to reveal the underlying molecular and cellular mechanisms linked to cancer initiation, progression, and metastasis.


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 = $871,685 )
2026	2026	UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL	55 LAKE AVE N	WORCESTER	MA	01655	WORCESTER	USA	Cancer Biology Research	000	2	6/11/2026	NON-COMPETING CONTINUATION	$871,685
														Subtotal = $871,685

Issue Date FY: 2025 ( Subtotal = $922,755 )
2025	2025	UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL	55 LAKE AVE N	WORCESTER	MA	01655	WORCESTER	USA	Cancer Biology Research	000	1	8/27/2025	NEW	$922,755
														Subtotal = $922,755

Grand Total All Awards = $1,794,440

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tRNA modification reprogramming and translational remodeling in cancer

Award Number: U01CA305187

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: COOPERATIVE AGREEMENT

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 08/28/2025

PERIOD OF PERFORMANCE END DATE: 07/31/2030

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