Tuesday, July 22, 2025 7/22/2025

Role of the tRNA methyltransferase AlkBH8 in Colorectal Cancer

Award Number: R21CA286898
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 03/01/2024
PERIOD OF PERFORMANCE END DATE: 02/28/2026

Group Awards By:

View Award Description

Role of the tRNA methyltransferase AlkBH8 in Colorectal Cancer - Project Summary: Reactive Oxygen Species (ROS) are produced as byproducts of oxidative phosphorylation and are found to be elevated in most cancers. In order to prevent ROS mediated cellular toxicity, cancer cells upregulate production of ROS detoxifying enzymes such as Glutathione Peroxidase 4 (GPx4). Essential to the catalytic activity of GPx4 is a catalytic selenocysteine residue, incorporated through specific reprogramming of the UGA-STOP codon by tRNA-selenocysteine (tRNASec). tRNASec requires chemical modification of its anticodon by the tRNA methyltransferase AlkBH8 for proper recognition and decoding ability of the UGA codon. Our preliminary data indicate that high levels of AlkBH8 are correlated with worse prognostic outcomes in colorectal cancer and that loss of AlkBH8 induces a growth arrest and reduces tumor forming ability in several colorectal cancer cell lines. However, at present almost nothing is known regarding the role of AlkBH8 and its tRNA modification in cancer cell growth and survival. Therefore, the studies proposed here are intended to fill a critical void in our understanding of tRNA modifications in cancer. First, we will use an inducible knockdown model of AlkBH8 to investigate the mechanisms following loss of AlkBH8 that lead to growth arrest and investigate whether this mechanism is conserved in in-vivo xenograft models. Second, we will utilize in-vitro analysis of recombinant AlkBH8 in order to deconvolute the contributions of each of its domains on its catalytic activity. The information generated through these studies will seek to establish a novel therapeutic target in one of the most frequently diagnosed and deadliest cancers across the world.


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: 2025 ( Subtotal = $174,483 )
2025	2025	REGENTS OF THE UNIVERSITY OF MICHIGAN	1109 GEDDES AVE STE 3300	ANN ARBOR	MI	48109	WASHTENAW	USA	Cancer Biology Research	001	2	5/22/2025	NON-COMPETING CONTINUATION	$17,448
2025	2025	REGENTS OF THE UNIVERSITY OF MICHIGAN	1109 GEDDES AVE STE 3300	ANN ARBOR	MI	48109	WASHTENAW	USA	Cancer Biology Research	000	2	3/3/2025	NON-COMPETING CONTINUATION	$157,035
														Subtotal = $174,483

Issue Date FY: 2024 ( Subtotal = $211,249 )
2024	2024	REGENTS OF THE UNIVERSITY OF MICHIGAN	1109 GEDDES AVE, SUITE 3300	ANN ARBOR	MI	48109	WASHTENAW	USA	Cancer Biology Research	000	1	2/28/2024	NEW	$211,249
														Subtotal = $211,249

Grand Total All Awards = $385,732

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Role of the tRNA methyltransferase AlkBH8 in Colorectal Cancer

Award Number: R21CA286898

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 03/01/2024

PERIOD OF PERFORMANCE END DATE: 02/28/2026

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer