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Investigating the mechanisms of erythroid lineage commitment in hematopoietic stem and multipotent progenitor populations

Award Number: K01DK120780
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

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Investigating the mechanisms of erythroid lineage commitment in hematopoietic stem and multipotent progenitor populations - PROJECT SUMMARY/ABSTRACT Elucidating the underlying mechanisms of lineage specification is not only a fundamental question of biology but also has a critical implication in therapeutic purpose. How initial erythroid lineage specification occurs in adult hematopoietic stem and multipotent progenitor populations has been largely unappreciated despite of its potential clinical significance to efficiently modulate erythroid cell production. Recent discoveries of lineage bias in hematopoietic stem cells (HSCs) and multipotent progenitors (MPPs) raises an intriguing possibility that early erythroid lineage priming occurs in HSC and MPP levels. This proposal aims to uncover the earliest erythroid lineage commitment events and their underlying mechanisms in HSCs and MPPs by investigating key extrinsic and intrinsic factors. First, I will identify the signaling pathways that are activated during the generation of erythroid cells in HSCs and MPPs using various in vitro and in vivo methods. Second, the role of endoplasmic reticulum (ER) stress signaling in erythroid lineage priming of MPP3 will be tested by molecular, cellular, and pharmacological approaches. Third, epigenetic regulation of erythroid priming in MPP2 will be investigated using omics analysis. This work will be conducted in the laboratory of Dr. Emmanuelle Passegue, internationally renowned HSC biologist and the director of the Columbia Stem Cell Initiative at Columbia University. My long- term career goal is to establish my independent research program constructing lineage specification networks of the blood system. To achieve this goal, as a first step, I will broaden my intellectual knowledge base and increase my technical skill repertoire through additional coursework/workshop/meetings and hands-on training. To aid in this process, I have assembled a mentoring and scientific advisory committee consisting of internationally renowned scientists with expertise in different areas relevant to my research and career goals. Collectively, the proposed studies will provide significant insight into the mechanisms of early erythroid lineage commitment and offer potential new strategies to control erythroid cell production. Moreover, this work will provide me with a solid foundation to establish my unique research program.


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: 2025 ( Subtotal = $0 )
2025	2023	WASHINGTON UNIVERSITY, THE	1 BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	11/13/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $226,452 )
2023	2023	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	003	3	8/15/2023	NON-COMPETING CONTINUATION	$0
2023	2023	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	004	3	8/19/2023	SUPPLEMENT FOR EXPANSION	$66,604
2023	2023	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	002	3	2/1/2023	NON-COMPETING CONTINUATION	$159,848
2023	2022	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63110	SAINT LOUIS CITY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	2	11/29/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$27,749
2023	2021	THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	11/29/2022	NEW	-$27,749
														Subtotal = $226,452

Issue Date FY: 2022 ( Subtotal = $159,848 )
2022	2022	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	2	9/15/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$159,848
2022	2021	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK, THE	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	9/15/2022	NEW	$0
														Subtotal = $159,848

Issue Date FY: 2021 ( Subtotal = $121,235 )
2021	2021	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK, THE	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	1/22/2021	NEW	$121,235
														Subtotal = $121,235

Grand Total All Awards = $507,535

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Investigating the mechanisms of erythroid lineage commitment in hematopoietic stem and multipotent progenitor populations

Award Number: K01DK120780

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

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