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The impact of inflammation on hematopoietic stem cell specification

Award Number: K01DK115661
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 09/08/2017
PERIOD OF PERFORMANCE END DATE: 02/28/2023

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The impact of inflammation on hematopoietic stem cell specification - Hematopoietic stem cells (HSCs) are rare cells within human bone marrow that are responsible both for the life-long replenishment of all blood cell lineages and for the curative effects of bone marrow transplantation. The creation of human induced pluripotent stem cells holds great promise for cellular regeneration therapies, but it is not currently possible to instruct these cells to generate HSCs in vitro. The goal of this application is to determine how pro-inflammatory signaling via NF-kB instructs HSC fate in the vertebrate embryo, and how this process is regulated by Progranulin a (Pgrna), with the ultimate goal of replicating HSC generation in vitro for clinical utility. My working hypothesis is that early pro-inflammatory inputs converge to activate NF-kB, which in turn activates key signaling events in the specification of HSC fate. These pro-inflammatory signals need to be downregulated soon after HSC specification; my preliminary results suggest that Pgrna functions in this manner. To test these hypotheses, this proposal consists of 2 aims: (1) Characterize the role of NF-kB in HSC specification; and (2) identify the role of Pgrna in HSC emergence. This study will be conducted in zebrafish, which are an ideal system for direct visualization of HSCs and have served as a model organism to study human disease. To achieve this application’s goals, novel transgenic and mutant lines will be generated, and qPCR, FACS-sorting, RNA-seq and confocal microscopy techniques will be utilized. Dr. Espin Palazon is a postdoctoral fellow in David Traver’s laboratory at UCSD whose ultimate career goal is to lead an independent research group focused on stem cells at a major research institution. Her short- term goals are (1) to determine the spatiotemporal requirements of NF-kB within hemogenic endothelium, and the downstream genes regulated to specify HSCs; and (2) to elucidate how Pgrna governs HSC emergence. She was recruited to join Dr. Traver’s group because of her strong background in immunology and the zebrafish animal model. The project outlined in this proposal will allow Dr. Espin Palazon to transition from a mentored scientific position to an independent research career, helping her gain expertise in FACS sorting, RNA-seq, genome editing techniques, and HSC biology, all of which are fundamental to establish her independent lab. Dr. Espin Palazon will meet and present her work to experts in development, immunology and hematology, in addition to presenting her data to a formal mentorship committee comprised of senior experts that will aid her transition to an independent researcher. UCSD offers numerous courses that Dr. Espin Palazon will attend, as well as seminars on career development and laboratory management. The vibrant, collaborative scientific atmosphere at UCSD is an ideal environment for Dr. Espin Palazon to develop during the mentored phase of her award, and will be instrumental in forming the foundation for the future success of these studies. She is well poised to execute the proposed work, achieve her career development and training goals and to contribute high impact research to the scientific community.


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 = -$5,238 )
2024	2021	IOWA STATE UNIVERSITY OF SCIENCE AND TECHNOLOGY	1350 BEARDSHEAR HALL	AMES	IA	50011	STORY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	5	11/2/2023	SUPPLEMENT FOR EXPANSION	-$1,746
2024	2021	IOWA STATE UNIVERSITY OF SCIENCE AND TECHNOLOGY	1350 BEARDSHEAR HALL	AMES	IA	50011	STORY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	5	11/2/2023	NON-COMPETING CONTINUATION	-$3,492
														Subtotal = -$5,238

Issue Date FY: 2021 ( Subtotal = $226,395 )
2021	2021	IOWA STATE UNIVERSITY OF SCIENCE AND TECHNOLOGY	515 MORRILL RD, 1350 BEARDSHEAR HALL	AMES	IA	50011	STORY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	5	9/1/2021	NON-COMPETING CONTINUATION	$150,930
2021	2021	IOWA STATE UNIVERSITY OF SCIENCE AND TECHNOLOGY	515 MORRILL RD, 1350 BEARDSHEAR HALL	AMES	IA	50011	STORY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	5	9/2/2021	SUPPLEMENT FOR EXPANSION	$75,465
														Subtotal = $226,395

Issue Date FY: 2020 ( Subtotal = $150,930 )
2020	2020	IOWA STATE UNIVERSITY OF SCIENCE AND TECHNOLOGY	515 MORRILL RD, 1350 BEARDSHEAR HALL	AMES	IA	50011	STORY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	002	4	8/19/2020	NON-COMPETING CONTINUATION	$150,930
2020	2019	IOWA STATE UNIVERSITY OF SCIENCE AND TECHNOLOGY	515 MORRILL RD, 1350 BEARDSHEAR HALL	AMES	IA	50011	STORY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	3	2/13/2020	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$5,223
2020	2018	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	2/13/2020	NON-COMPETING CONTINUATION	-$5,223
														Subtotal = $150,930

Issue Date FY: 2019 ( Subtotal = $150,930 )
2019	2019	IOWA STATE UNIVERSITY OF SCIENCE AND TECHNOLOGY	515 MORRILL RD, 1350 BEARDSHEAR HALL	AMES	IA	50011	STORY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	3	9/11/2019	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$150,930
2019	2018	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR DEPT 621	LA JOLLA	CA	92093	SAN DIEGO	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	9/10/2019	NON-COMPETING CONTINUATION	$0
														Subtotal = $150,930

Issue Date FY: 2018 ( Subtotal = $159,555 )
2018	2018	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR DEPT 621	LA JOLLA	CA	92093	SAN DIEGO	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	2	9/19/2018	NON-COMPETING CONTINUATION	$11,819
2018	2018	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR DEPT 621	LA JOLLA	CA	92093	SAN DIEGO	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	9/6/2018	NON-COMPETING CONTINUATION	$147,736
														Subtotal = $159,555

Issue Date FY: 2017 ( Subtotal = $146,490 )
2017	2017	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR DEPT 621	LA JOLLA	CA	92093	SAN DIEGO	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	9/8/2017	NEW	$146,490
														Subtotal = $146,490

Grand Total All Awards = $829,062

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The impact of inflammation on hematopoietic stem cell specification

Award Number: K01DK115661

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 09/08/2017

PERIOD OF PERFORMANCE END DATE: 02/28/2023

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