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

Mechanisms of STAT1 and STAT3 canonical and persistent activation in physiology and disease

Award Number: R01AI191107
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: 03/01/2025
PERIOD OF PERFORMANCE END DATE: 02/28/2030

Group Awards By:

View Award Description

Mechanisms of STAT1 and STAT3 canonical and persistent activation in physiology and disease - Summary Rapid plasma membrane-to-nucleus relocalization of Signal Transducer and Activator of Transcription (STAT) family members upon cytokines stimulation is vital for signal transduction. Countless cell processes, including immune cell’s ability to fight pathogens, depend directly on STAT signaling. Extracellular signals typically result in STAT phosphorylation, triggering a conformational change that leads to importin recruitment and nuclear translocation. In the nucleus, STATs function as transcription factors, inducing the expression of a plethora of genes involved in native immunity, survival, cell growth, proliferation, and pathogen response. Gain-of-function (GOF) mutations in STAT1 and STAT3 are associated with various immunodeficiencies characterized by over- activated immune cells, autoimmunity, and increased risk of infections. This proposal focuses on STAT1 and STAT3. Leveraging the power of cryogenic electron microscopy and biochemical, biophysical, and cellular methodologies, we aim to illuminate what constitutes a knowledge gap at the center of innate antimicrobial protection in STAT signaling. Aim 1 will decipher the mechanisms activated STAT1 and STAT3 enter the cell nucleus under physiological conditions. STATs do not have a classical Nuclear Localization Signal (NLS) yet use importin α/β and the GTPase Ran for nuclear entry. The molecular mechanisms of STAT nuclear import have not been elucidated and appear to differ in different STAT family members. Understanding STAT’s quaternary structure is crucial in deciphering how the nuclear import machinery is recruited without a classical NLS. Aim 2 will catalog GOF mutations identified in STAT1 and STAT3 and examine their impact on STAT quaternary structure, NLS exposure, and nuclear signaling, establishing a causative relationship between GOF mutations and persistent nuclear activation of STAT1 and STAT3. Our integrative approach to molecularly characterize STAT1 and STAT3 GOF mutations based on genotype- phenotype correlations will generate a comprehensive atlas of all known mutations discovered thus far.


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 = $646,763 )
2026	2026	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH STREET	BIRMINGHAM	AL	35294	JEFFERSON	USA	Allergy and Infectious Diseases Research	000	2	2/11/2026	NON-COMPETING CONTINUATION	$646,763
														Subtotal = $646,763

Issue Date FY: 2025 ( Subtotal = $639,485 )
2025	2025	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH STREET	BIRMINGHAM	AL	35294	JEFFERSON	USA	Allergy and Infectious Diseases Research	000	1	2/25/2025	NEW	$639,485
														Subtotal = $639,485

Grand Total All Awards = $1,286,248

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Mechanisms of STAT1 and STAT3 canonical and persistent activation in physiology and disease

Award Number: R01AI191107

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: 03/01/2025

PERIOD OF PERFORMANCE END DATE: 02/28/2030

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer