Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

Characterization of eye pathology associated with the understudied protein TDRD7 linked to a human syndrome

Award Number: R03TR006304
ORGANIZATION: NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 06/01/2026
PERIOD OF PERFORMANCE END DATE: 05/31/2027

Group Awards By:

View Award Description

Characterization of eye pathology associated with the understudied protein TDRD7 linked to a human syndrome - SUMMARY We discovered mutations in Tudor family RNA-binding protein (RBP) TDRD7 (OMIM: 611258) cause congenital birth defect cataract–loss of eye lens transparency–in humans. We linked TDRD7 to defects in sperm formation, leading to the recognition of a rare novel human syndrome that includes congenital cataract and azoopermia as symptoms. Cataract occurs in neonates as a rare condition, but causes permanent vision damage, with surgery being the only treatment. Even after surgery, patients face eye complications throughout life. Thus, new therapies are urgently needed. Yet, knowledge on TDRD7, especially on its function in the eye, is limited. Thus, we will address this critical knowledge-gap by identifying potential new druggable pathways linked to TDRD7. Lens differentiation upregulates select RNAs/proteins while they undergo dramatic cell-shape changes–involving ~1000-fold length-wise increase–and migration toward lens core. A long-standing question is, what mechanisms control these complex cellular differentiation events? Our data suggests the involvement of TDRD7. TDRD7 protein has OST-HTH/LOTUS and Tudor domains that may allow it to associate with RNA and methylated arginine/lysine, respectively. Our data shows Tdrd7 knockout mice (Tdrd7KO) exhibit cataract and reduced expression of genes linked to human/animal lens defects. Further, Tdrd7 loss causes severe cellular morphology defects in mature lens fibers. Our data shows that in addition to abundant Tdrd7 protein in the fiber cytoplasm, where it participates in protein-RNA complexes, Tdrd7 protein also enters fiber nucleus beginning at midembryonic stages. These exciting findings lead to a paradigm-shifting hypothesis: TDRD7 may participate in both (1) post-transcriptional control and (2) chromatin control, to facilitate proper gene expression regulation in the lens. This will be tested by pursuing the following goals: Characterize spatiotemporal chromatin and transcriptome changes in Tdrd7KO mouse lens at the single-nucleus level and use AI-based approaches to derive regulatory networks (Aim 1). Characterize the impact of Tdrd7-loss on lens proteome and identify its protein interactions in normal lens (Aim 2). This innovative proposal will fundamentally advance knowledge on TDRD7 by: (1) defining, on single nucleus level, spatiotemporal changes in lens transcriptome and (2) changes in lens chromatin, upon Tdrd7 loss, (3) defining proteins impacting Tdrd7 function and those altered in Tdrd7KO, and (4) making this regulatory information publicly available via a web-based, user-friendly resource iSyTE for continued eye gene discovery. We will collaborate with Dr. Shinichiro Chuma (Kyoto University, Japan) who is an expert on TDRD-proteins and has developed a Tdrd7 knockout (KO) mouse model that we will investigate. While the facilities in US and Japan are similar, the targeted Tdrd7KO mouse model is not commercially available in the US and Dr. Chuma’s 20 years expertise on TDRD-proteins (e.g. advise on Tdrd7 biochemical protocols) is necessary for success of the aims. This translational research will advance knowledge on an understudied protein, TDRD7, and identify potential new drug targets/pathways for novel therapies/treatments for cataract birth defect.


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 = $158,430 )
2026	2026	UNIVERSITY OF DELAWARE	550 S COLLEGE AVE	NEWARK	DE	19713	NEW CASTLE	USA	National Center for Advancing Translational Sciences	000	1	5/8/2026	NEW	$158,430
														Subtotal = $158,430

Grand Total All Awards = $158,430

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Characterization of eye pathology associated with the understudied protein TDRD7 linked to a human syndrome

Award Number: R03TR006304

ORGANIZATION: NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 06/01/2026

PERIOD OF PERFORMANCE END DATE: 05/31/2027

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer