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MINING OF REVERSE TRANSCRIPTASE INHIBITOR TREATED PATIENT DATA TO IDENTIFY LINE-1 RETROTRANSPOSON ROLE IN HUMAN DISEASES

Award Number: R03CA310697
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/03/2026
PERIOD OF PERFORMANCE END DATE: 06/30/2028

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MINING OF REVERSE TRANSCRIPTASE INHIBITOR TREATED PATIENT DATA TO IDENTIFY LINE-1 RETROTRANSPOSON ROLE IN HUMAN DISEASES - Abstract The proposed research aims to investigate the role of LINE-1 (L1) retrotransposons in human diseases by mining patient data from the NYU Langone database, which includes approximately 4.8 million patients. L1 retrotransposons are genetic elements capable of moving within the human genome and normally repressed by the host. When de-repressed as for most of human cancers, L1 elements have been shown to activate an innate antiviral response, which have been shown to play a role in aging, neurodegenerative diseases, autoimmune diseases, and various cancers such as mammary, prostate, colon, and pancreatic cancers. Reverse Transcriptase (RT) inhibitors, originally developed for HIV treatment, have been shown to also repress L1 activity and few studies have associated their use with lower incidences of certain diseases in treated patients. Moreover, the recent introduction and large-scale use of Pre-Exposure Prophylaxis (PrEP) treatments created a pool of non-infected individuals treated with RT inhibitors; these patients are highly represented in our database and constitute an invaluable resource for the identification of novel physiological and disease processes in which L1 plays a role. Research Design and Methods: We propose to mine the NYU Langone patient database and integrate these analyses with molecular data from CPTAC and TCGA databases. The study will conduct comparative analyses to identify differences in disease incidence between RT inhibitor-treated and control cohorts. Statistical methods will be employed to analyze these differences, initially focusing on features previously linked in in vitro or in vivo studies to L1 activity such as anemia development during pregnancy, prostate, mammary and pancreatic cancers. Effect of RT inhibitors on autoimmune and neurodegenerative diseases, wound healing and potential sex-specific effects will also be considered. Unbiased comparisons will also be applied to identify additional differences between RT treated and control cohorts. The goal is to generate hypotheses about L1's role in human diseases and explore the therapeutic potential of RT inhibitors for non-HIV related conditions. Significance: The research design and methods are structured to identify unexplored roles of L1 retrotransposons in human diseases and the potential therapeutic benefits of RT inhibitors. The findings could lead to novel insights into disease mechanisms and inform the development of new treatment strategies leveraging RT inhibitors for non- HIV related conditions.


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 = $169,500 )
2026	2026	NEW YORK UNIVERSITY	550 1ST AVE	NEW YORK	NY	10016	NEW YORK	USA	Cancer Treatment Research	000	1	7/7/2026	NEW	$169,500
														Subtotal = $169,500

Grand Total All Awards = $169,500

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MINING OF REVERSE TRANSCRIPTASE INHIBITOR TREATED PATIENT DATA TO IDENTIFY LINE-1 RETROTRANSPOSON ROLE IN HUMAN DISEASES

Award Number: R03CA310697

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 07/03/2026

PERIOD OF PERFORMANCE END DATE: 06/30/2028

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