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

Mechanistic insights into a novel cell cycle regulator complex for cancer therapy

Award Number: R01AI198900
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 05/07/2026
PERIOD OF PERFORMANCE END DATE: 04/30/2031

Group Awards By:

View Award Description

Mechanistic insights into a novel cell cycle regulator complex for cancer therapy - PROJECT SUMMARY Ribosomes are essential molecular machines that translate genetic information into proteins—a process especially critical in the immune system, where rapid cell proliferation, differentiation, and effector functions are necessary to maintain immune homeostasis and respond to pathogenic threats. Although ribosome biogenesis is central to immune cell function, the mechanisms regulating this process—and the consequences of their disruption—remain poorly defined. This gap in knowledge is clinically significant: enhanced ribosome production can drive malignancy and autoimmunity, while impaired biogenesis can lead to immune deficiency and cytopenia. Using unbiased germline mutagenesis and biochemical approaches, we have identified a novel nuclear complex composed of two previously uncharacterized zinc finger transcription factors, ZFP574 and THAP12. Loss of either factor destabilizes the other and leads to severe immune dysfunction, including pan-cytopenia and G1–S phase cell cycle arrest. Remarkably, neither ZFP574 nor THAP12 was previously known to regulate transcription. Our preliminary data reveal that this complex acts as a transcriptional activator of Polr1h, a core subunit of RNA Polymerase I (Pol I), which is predicted to contribute to the proofreading of rDNA–rRNA hybrids. Loss of either protein selectively downregulates Polr1h expression in lymphocytes—without affecting other Pol I subunits— suggesting a targeted mechanism that sustains rRNA synthesis and ribosome biogenesis. We hypothesize that ZFP574–THAP12–mediated regulation of Polr1h is essential for RNA Pol I function and immune cell competence. To test this, we will: (1) define the mechanisms by which the ZFP574–THAP12 complex supports immune development and function; and (2) evaluate the therapeutic potential of targeting this pathway in models of leukemia and autoimmunity. Relevance to public health: Signaling pathways that sustain lymphocyte survival are often hijacked in leukemia and autoimmune disease. There is a critical need for therapies that selectively disrupt these pro-survival programs. This project investigates a newly identified transcriptional complex essential for immune cell function and ribosome production, offering a novel therapeutic target in diseases marked by immune overactivation or malignant transformation.


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 = $415,000 )
2026	2026	THE UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Allergy and Infectious Diseases Research	000	1	5/11/2026	NEW	$415,000
														Subtotal = $415,000

Grand Total All Awards = $415,000

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Mechanistic insights into a novel cell cycle regulator complex for cancer therapy

Award Number: R01AI198900

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 05/07/2026

PERIOD OF PERFORMANCE END DATE: 04/30/2031

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer