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

Inflammatory Bowel Disease Susceptibility Gene Regulation of Anemia

Award Number: R21AI152017
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: 03/03/2021
PERIOD OF PERFORMANCE END DATE: 02/28/2023

Group Awards By:

View Award Description

Inflammatory Bowel Disease Susceptibility Gene Regulation of Anemia - SUMMARY Anemia resulting from iron deficiency is the most frequent extraintestinal manifestation of inflammatory bowel disease (IBD) and can significantly impact patient health and quality of life. However, the mechanisms of iron deficiency associated with IBD are poorly understood. Moreover, the contributions of susceptibility genes associated with increased risk of IBD to the development of anemia are virtually unknown. Protein tyrosine phosphatase non-receptor type 2 (PTPN2) loss-of-function mutations are genetic markers of increased IBD risk. This proposal builds on our novel preliminary data identifying that in a proteomic screen of serum from PTPN2- genotyped IBD patients, altered expression of iron-handling proteins was the #1 pathway modified in IBD patients harboring the rs1893217 PTPN2 loss-of-function risk allele, independent of disease severity. We also show that Ptpn2-deficient mice have anemia. We hypothesize that PTPN2 is a critical regulator of iron handling mechanisms and that loss of PTPN2 activity disrupts iron homeostasis and metabolism. The goal of this study is to translate patient biomarker findings into experimental models to mechanistically explore PTPN2 regulation of iron transport, and understand how PTPN2 loss of function may contribute to iron deficiency in IBD. To dissect the mechanisms by which PTPN2 regulates iron homeostasis, we will focus on PTPN2 regulation of two essential cell types that are critically important for iron homeostasis. Intestinal epithelial cells are responsible for the only entry route for iron into the body: absorption by intestinal epithelial cells, while macrophages are responsible for capturing and recycling iron from the breakdown of erythrocytes. In Aim 1, we will identify the role of PTPN2 in regulating intestinal epithelial iron uptake by measuring iron absorption and exit in vivo and in vitro using enteroids from constitutive and inducible intestinal epithelial-specific Ptpn2 knockout mice. We will also determine how PTPN2 regulates molecular pathways involved in iron transport and metabolism. In Aim 2, we will identify the mechanisms of PTPN2 regulation of macrophage iron handling by determining how PTPN2 deficiency alters iron recycling and regulation of essential iron- handling proteins using macrophage-specific PTPN2 knockout mice and CRISPR-modified human macrophages expressing the clinical PTPN2 loss-of-function rs1893217 risk allele. Expected Outcomes & Impact: These studies will translate findings in PTPN2-genotyped patients to complementary in vivo and in vitro model systems. We will not only generate fundamental and highly novel insights into PTPN2 regulation of iron homeostasis and its potential role as a complicating factor in anemia associated with IBD, but will also identify novel targets for intervention.


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: 2024 ( Subtotal = $0 )
2024	2022	REGENTS OF THE UNIVERSITY OF CALIFORNIA AT RIVERSIDE	200 UNIVERSTY OFC BUILDING	RIVERSIDE	CA	92521	RIVERSIDE	USA	Allergy and Infectious Diseases Research	000	2	1/22/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $194,375 )
2022	2022	REGENTS OF THE UNIVERSITY OF CALIFORNIA AT RIVERSIDE	900 UNIVERSITY AVE	RIVERSIDE	CA	92521	RIVERSIDE	USA	Allergy and Infectious Diseases Research	000	2	2/28/2022	NON-COMPETING CONTINUATION	$194,375
														Subtotal = $194,375

Issue Date FY: 2021 ( Subtotal = $233,250 )
2021	2021	REGENTS OF THE UNIVERSITY OF CALIFORNIA AT RIVERSIDE	200 UNIVERSTY OFFICE BLDG	RIVERSIDE	CA	92521	RIVERSIDE	USA	Allergy and Infectious Diseases Research	000	1	3/3/2021	NEW	$233,250
														Subtotal = $233,250

Grand Total All Awards = $427,625

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Inflammatory Bowel Disease Susceptibility Gene Regulation of Anemia

Award Number: R21AI152017

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: 03/03/2021

PERIOD OF PERFORMANCE END DATE: 02/28/2023

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer