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microRNA-22 and the microRNA-22/TET2 Network as Regulators of the Cell Fate Decision in Hematopoietic Stem Cells and in the Development of Myelodysplastic Syndrome.

Award Number: F30DK108532
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

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¿ DESCRIPTION (provided by applicant): At the root of the hematopoietic system are long-term hematopoietic stem cells (LT-HSCs), an exceedingly rare population of multi-potent cells capable of self-renewal. Hematopoietic differentiation is accomplished through stably propagated changes to gene expression that are mediated by epigenetic factors, such as DNA methylation and chromatin remodeling, and the expression of microRNAs. Mutation and dysregulation of epigenetic effector genes, such as TET2 and DNMT3a, and aberrant microRNA expression have been implicated in hematological malignancies. Myelodysplastic syndrome (MDS) is an incurable stem cell disorder that is characterized by ineffective hematopoiesis and a risk of transformation to myeloid leukemia, and is frequently associated with abnormal DNA methylation. TET2, or tet methylcytosine dioxygenase 2, oxidizes the repressive 5-methylcytosine (5-mC) mark to 5-hydroxymethylcytosine (5-hmC), the first step in removing DNA methylation. microRNA-22 (miR-22) is highly expressed in MDS and is associated with poor survival rates. In mice, miR-22 over-expression reduces global 5-hmC through repression of its target, Tet2, increases the self-renewal capacity of HSCs, and results in the development of an MDS-like disease. Using recent advances in the ability to profile genome-wide cytosine hydroxymethylation, we seek to identify specific targets of the miR-22/TET2 regulatory network in HSCs that contribute to the development of MDS. We also aim to describe miR-22's role as a mediator of normal hematopoiesis using a novel reporter of miR-22 expression. Finally, we aim to identify the potential for the inhibition of miR-22 in the treatment of MDS using recently acquired miR-22 knockout mice. The successful completion of this work will provide essential insights into the roles of microRNAs and epigenetic changes in the regulation of hematopoietic stem cell fate and the pathogenesis of hematological diseases, and may ultimately impact the treatment of poor-prognosis MDS.


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: 2022 ( Subtotal = -$1,898 )
2022	2019	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	002	5	4/22/2022	NON-COMPETING CONTINUATION	-$1,898
2022	2018	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	4	4/22/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
2022	2018	ALBERT EINSTEIN COLLEGE OF MEDICINE, INC.	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	4/22/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = -$1,898

Issue Date FY: 2021 ( Subtotal = -$2,827 )
2021	2019	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	5	12/22/2020	NON-COMPETING CONTINUATION	-$2,827
														Subtotal = -$2,827

Issue Date FY: 2019 ( Subtotal = $50,016 )
2019	2019	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	002	5	7/3/2019	NON-COMPETING CONTINUATION	$50,016
2019	2018	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	4	2/7/2019	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$24,331
2019	2018	ALBERT EINSTEIN COLLEGE OF MEDICINE, INC.	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	2/7/2019	NON-COMPETING CONTINUATION	-$24,331
														Subtotal = $50,016

Issue Date FY: 2018 ( Subtotal = $49,524 )
2018	2018	ALBERT EINSTEIN COLLEGE OF MEDICINE, INC.	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	7/2/2018	NON-COMPETING CONTINUATION	$49,524
														Subtotal = $49,524

Issue Date FY: 2017 ( Subtotal = $49,044 )
2017	2017	ALBERT EINSTEIN COLLEGE OF MEDICINE, INC.	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	7/3/2017	NON-COMPETING CONTINUATION	$49,044
														Subtotal = $49,044

Issue Date FY: 2016 ( Subtotal = $48,576 )
2016	2016	ALBERT EINSTEIN COLLEGE OF MEDICINE INC	111 E 210TH ST	BRONX	NY	10467	BRONX	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	7/19/2016	NEW	$48,576
2016	2016	ALBERT EINSTEIN COLLEGE OF MEDICINE INC	111 E 210TH ST	BRONX	NY	10467	BRONX	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	1	7/19/2016	NEW	$0
														Subtotal = $48,576

Grand Total All Awards = $192,435

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microRNA-22 and the microRNA-22/TET2 Network as Regulators of the Cell Fate Decision in Hematopoietic Stem Cells and in the Development of Myelodysplastic Syndrome.

Award Number: F30DK108532

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

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