Wednesday, February 18, 2026 2/18/2026

Role of FGF23 in Bone, Kidney, Blood, Crosstalk in Sickle Cell Disease Mice

Award Number: R01DK129431
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/01/2022
PERIOD OF PERFORMANCE END DATE: 01/31/2027

Group Awards By:

View Award Description

Role of FGF23 in Bone, Kidney, Blood, Crosstalk in Sickle Cell Disease Mice - Summary Sickle cell disease (SCD) is a hemoglobinopathy associated with severe bone abnormalities including osteoporosis. Eighty percent of SCD adults have low bone mineral density (BMD) that is independent of risk factors such as age, gender, and menopausal status, suggesting the etiology of osteoporosis in SCD differs from the general population. Proposed contributing factors to bone loss in SCD include marrow hyperplasia secondary to chronic anemia, inflammation, ischemia, and vitamin D deficiency. However, the mechanisms of bone loss in SCD subjects has not been fully investigated, and there are no targeted therapies. Hormonal fibroblast growth factor 23 (FGF23), which controls phosphate homeostasis and has direct and indirect effects on bone mineralization, is reported to be increased in human anemia. Based on our exciting preliminary data showing that increased serum FGF23 and hypophosphatemia in humanized Townes SCD mice, which are anemic but not in renal failure, and that in vitro and in vivo FGF23 blockade partially rescues impaired mineralization and improved reduced BMD in SCD mice, we posit that cross-talk involving bone marrow erythropoiesis, kidney, and bone contributes to osteoporosis in SCD mice. Specifically, we posit that 1) sickling of red blood cells and the resulting anemia causes increased erythropoietin production by the kidney, which increases bone FGF23 production that impairs phosphate reabsorption; and 2) anemia-induced FGF23 results in impaired osteoblast differentiation, mineralization, and bone strength in SCD mice due to hypophosphatemia and pyrophosphate abnormalities via impaired sodium phosphate transporters PIT1 and PIT2 signaling in bone. Furthermore, increased FGF23 reduces PIT1 signaling that can interfere with erythrocyte differentiation, further perpetuating the anemic state. To test our hypotheses, we propose the following Specific Aims: Aim 1: Examine the molecular mechanisms by which FGF23 contributes to phosphate wasting in SCD Mice; Aim 2: Assess the molecular mechanism by which FGF23 contributes to impaired bone mineralization in SCD mice; and Aim 3: Determine whether FGF23 neutralizing antibody modulates the anemia phenotype of SCD mice. Our proposed studies may identify FGF23 as a novel contributor to the pathogenesis of bone loss and anemia in SCD mice. Since the FGF23Ab is now FDA approved for the treatment of X-linked hypophosphatemia, it may also be a useful therapy to prevent bone loss and improve anemia in human SCD in the future.


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 = $0 )
2026	2025	UNIVERSITY OF CONNECTICUT HEALTH CENTER	263 FARMINGTON AVE	FARMINGTON	CT	06030	CAPITOL	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	4	1/12/2026	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2025 ( Subtotal = $498,828 )
2025	2025	UNIVERSITY OF CONNECTICUT HEALTH CENTER	263 FARMINGTON AVE	FARMINGTON	CT	06030	CAPITOL	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	4	1/22/2025	NON-COMPETING CONTINUATION	$498,828
														Subtotal = $498,828

Issue Date FY: 2024 ( Subtotal = $532,082 )
2024	2024	UNIVERSITY OF CONNECTICUT HEALTH CENTER	263 FARMINGTON AVE	FARMINGTON	CT	06030	CAPITOL	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	1/26/2024	NON-COMPETING CONTINUATION	$498,828
2024	2024	UNIVERSITY OF CONNECTICUT HEALTH CENTER	263 FARMINGTON AVE	FARMINGTON	CT	06030	CAPITOL	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	3	5/6/2024	NON-COMPETING CONTINUATION	$33,254
														Subtotal = $532,082

Issue Date FY: 2023 ( Subtotal = $554,253 )
2023	2023	UNIVERSITY OF CONNECTICUT	263 FARMINGTON AVE, ASB #3	FARMINGTON	CT	06032	CAPITOL	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	2/7/2023	NON-COMPETING CONTINUATION	$554,253
														Subtotal = $554,253

Issue Date FY: 2022 ( Subtotal = $548,480 )
2022	2022	UNIVERSITY OF CONNECTICUT	263 FARMINGTON AVE, ASB #3	FARMINGTON	CT	06032	CAPITOL	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	3/25/2022	NEW	$548,480
														Subtotal = $548,480

Grand Total All Awards = $2,133,643

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Role of FGF23 in Bone, Kidney, Blood, Crosstalk in Sickle Cell Disease Mice

Award Number: R01DK129431

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 04/01/2022

PERIOD OF PERFORMANCE END DATE: 01/31/2027

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer