Monday, June 30, 2025 6/30/2025

Understanding the variability in nonsense-mediated RNA decay

Award Number: R35GM133433
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/01/2019
PERIOD OF PERFORMANCE END DATE: 12/31/2029

Group Awards By:

View Award Description

Understanding the variability in nonsense-mediated RNA decay - PROJECT SUMMARY Predicting functional consequences of genomic variation remains the biggest barrier to precision medicine. While nonsense variants are considered the best understood of all genetic variants, our work has revealed significant gaps in our knowledge base for their functional interpretation. My group studies how variability in mRNA surveillance impacts the functional consequence of human genetic variants. Protein-truncating genetic variants often cause loss of gene function because their encoding transcripts are subject to degradation by an RNA quality control process called nonsense-mediated RNA decay (NMD). NMD senses transcripts with a premature stop codon and triggers their degradation to prevent the production of truncated proteins. However, the efficiency with which NMD acts on a target transcript is variable across genes, tissues, and even individuals. We have shown that non-canonical translation events such as stop codon readthrough and translation reinitiation can cause NMD evasion by a nonsense-containing transcript, though the rules governing such events are unknown. My research program builds on these discoveries to systematically investigate factors that cause variable NMD efficiency. Specifically, we combine massively parallel reporter assays with targeted gene editing to identify and validate sequence features that permit NMD escape. Through this work, we aspire to build new rules for the functional classification of variants and use such rubrics to build more accurate and predictive models for phenotypic consequence of nonsense variants. Such a model will allow us to identify variants that are likely to cause disease and to develop novel therapeutic approaches to counter genetic disorders.


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 = $417,177 )
2025	2025	THE REGENTS OF THE UNIV. OF COLORADO	13001 E 17TH PL STE F428	AURORA	CO	80045	ADAMS	USA	Biomedical Research and Research Training	005	6	5/27/2025	COMPETING CONTINUATION	$0
2025	2025	THE REGENTS OF THE UNIV. OF COLORADO	13001 E 17TH PL STE F428	AURORA	CO	80045	ADAMS	USA	Biomedical Research and Research Training	004	6	5/15/2025	COMPETING CONTINUATION	$92
2025	2025	THE REGENTS OF THE UNIV. OF COLORADO	13001 E 17TH PL STE F428	AURORA	CO	80045	ADAMS	USA	Biomedical Research and Research Training	001	6	1/31/2025	COMPETING CONTINUATION	$417,177
2025	2023	THE REGENTS OF THE UNIV. OF COLORADO	13001 E 17TH PL STE F428	AURORA	CO	80045	ADAMS	USA	Biomedical Research and Research Training	002	5	5/15/2025	NON-COMPETING CONTINUATION	-$61
2025	2023	THE REGENTS OF THE UNIV. OF COLORADO	13001 E 17TH PL STE F428	AURORA	CO	80045	ADAMS	USA	Biomedical Research and Research Training	003	5	5/15/2025	SUPPLEMENT FOR EXPANSION	-$31
2025	2023	THE REGENTS OF THE UNIV. OF COLORADO	13001 E 17TH PL STE F428	AURORA	CO	80045	ADAMS	USA	Biomedical Research and Research Training	000	5	1/27/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $417,177

Issue Date FY: 2023 ( Subtotal = $579,182 )
2023	2023	REGENTS OF THE UNIVERSITY OF COLORADO, THE	13001 E 17TH PLACE F428	AURORA	CO	80045	ADAMS	USA	Biomedical Research and Research Training	000	5	7/11/2023	NON-COMPETING CONTINUATION	$382,091
2023	2023	REGENTS OF THE UNIVERSITY OF COLORADO, THE	13001 E 17TH PLACE F428	AURORA	CO	80045	ADAMS	USA	Biomedical Research and Research Training	001	5	7/28/2023	SUPPLEMENT FOR EXPANSION	$197,091
														Subtotal = $579,182

Issue Date FY: 2022 ( Subtotal = $382,091 )
2022	2022	REGENTS OF THE UNIVERSITY OF COLORADO, THE	13001 E 17TH PLACE F428	AURORA	CO	80045	ADAMS	USA	Biomedical Research and Research Training	000	4	7/19/2022	NON-COMPETING CONTINUATION	$382,091
														Subtotal = $382,091

Issue Date FY: 2021 ( Subtotal = $382,091 )
2021	2021	REGENTS OF THE UNIVERSITY OF COLORADO, THE	13001 E 17TH PLACE F428	AURORA	CO	80045	ADAMS	USA	Biomedical Research and Research Training	000	3	7/7/2021	NON-COMPETING CONTINUATION	$382,091
														Subtotal = $382,091

Issue Date FY: 2020 ( Subtotal = $582,867 )
2020	2020	REGENTS OF THE UNIVERSITY OF COLORADO, THE	13001 E 17TH PLACE F428	AURORA	CO	80045	ADAMS	USA	Biomedical Research and Research Training	000	1	1/22/2020	SUPPLEMENT FOR EXPANSION	$41,209
2020	2020	REGENTS OF THE UNIVERSITY OF COLORADO, THE	13001 E 17TH PLACE F428	AURORA	CO	80045	ADAMS	USA	Biomedical Research and Research Training	002	2	8/21/2020	SUPPLEMENT FOR EXPANSION	$77,150
2020	2020	REGENTS OF THE UNIVERSITY OF COLORADO, THE	13001 E 17TH PLACE F428	AURORA	CO	80045	ADAMS	USA	Biomedical Research and Research Training	001	2	7/27/2020	NON-COMPETING CONTINUATION	$464,508
														Subtotal = $582,867

Issue Date FY: 2019 ( Subtotal = $382,091 )
2019	2019	REGENTS OF THE UNIVERSITY OF COLORADO, THE	13001 E 17TH PLACE F428	AURORA	CO	80045	ADAMS	USA	Biomedical Research and Research Training	000	1	7/24/2019	NEW	$382,091
														Subtotal = $382,091

Grand Total All Awards = $2,725,499

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Understanding the variability in nonsense-mediated RNA decay

Award Number: R35GM133433

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 08/01/2019

PERIOD OF PERFORMANCE END DATE: 12/31/2029

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer