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Integrative analysis to identify genomic biomarkers in HPV positive oral cancer

Award Number: R03DE030580
ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 05/01/2023
PERIOD OF PERFORMANCE END DATE: 04/30/2025

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Integrative analysis to identify genomic biomarkers in HPV positive oral cancer - PROJECT SUMMARY/ABSTRACT Human papillomavirus positive (HPV+) oral cancer (OC), accounting for over 70% of oropharyngeal cancer cases in North America and Europe, was found to be more aggressive with a higher tendency of metastasis compared to HPV negative OC. It is believed that such aggressiveness is associated to the nature of its oncogenic mechanisms triggered by HPV infection. HPV encodes two potent oncogenes E6 and E7 that inactivate key tumor suppressors pRb and p53 and subsequently alter the expression spectrum of genes in oral epithelial cells. To identify the molecular mechanisms of HPV oncogenesis, numerous studies have compared the (epi)genomic profiles of HPV+ OC to normal oral epithelium, HPV negative OC, or other cancer types. These studies have generated high-throughput sequencing datasets using different methods (transcriptomic, genomic and epigenomic) and cellular conditions (normal, viral-infected and cancerous). However, these datasets were not fully explored due to lack of comparable analysis platform to efficiently interrogate them, especially when heterogeneity and batch effects are high across studies. We propose to leverage our data science experience as well as close wet-lab collaborations to perform integrative analysis to identify HPV-specific biomarkers in HPV+ OC. We propose to integrate (epi)genomic next generation sequencing datasets from 11 selected studies (with addition if more availability in the future), involving 3 data types, 13 cell lines, 3 viral infection stages and 2 anatomically similar sites. At the core of the analysis is to remove potential batch effects and biases of the integrated datasets and to set proper controls to nominate oncogenic biomarkers. To validate the findings, we propose both dry and wet-lab experiments to evaluate candidate biomarkers. Insights from the proposed study could advance our understanding of oral biology and potentially translate to novel therapeutics for HPV+ OC.


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 = -$2,090 )
2025	2024	H. LEE MOFFITT CANCER CENTER AND RESEARCH INSTITUTE HOSPITAL, INC.	12902 USF MAGNOLIA DR	TAMPA	FL	33612	HILLSBOROUGH	USA	Oral Diseases and Disorders Research	000	2	8/28/2025	NON-COMPETING CONTINUATION	-$2,090
														Subtotal = -$2,090

Issue Date FY: 2024 ( Subtotal = $168,500 )
2024	2024	H. LEE MOFFITT CANCER CENTER AND RESEARCH INSTITUTE HOSPITAL, INC.	12902 USF MAGNOLIA DR	TAMPA	FL	33612	HILLSBOROUGH	USA	Oral Diseases and Disorders Research	000	2	4/8/2024	NON-COMPETING CONTINUATION	$151,650
2024	2024	H. LEE MOFFITT CANCER CENTER AND RESEARCH INSTITUTE HOSPITAL, INC.	12902 USF MAGNOLIA DR	TAMPA	FL	33612	HILLSBOROUGH	USA	Oral Diseases and Disorders Research	001	2	6/6/2024	NON-COMPETING CONTINUATION	$16,850
														Subtotal = $168,500

Issue Date FY: 2023 ( Subtotal = $168,500 )
2023	2023	H. LEE MOFFITT CANCER CENTER AND RESEARCH INSTITUTE HOSPITAL, INC.	12902 MAGNOLIA DR	TAMPA	FL	33612	HILLSBOROUGH	USA	Oral Diseases and Disorders Research	000	1	4/10/2023	NEW	$168,500
														Subtotal = $168,500

Grand Total All Awards = $334,911

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Integrative analysis to identify genomic biomarkers in HPV positive oral cancer

Award Number: R03DE030580

ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 05/01/2023

PERIOD OF PERFORMANCE END DATE: 04/30/2025

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