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Investigating the functional roles of CTSH and PGM1 in beta-cells during autoimmune diabetes development

Award Number: K01DK131329
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 02/01/2022
PERIOD OF PERFORMANCE END DATE: 01/31/2027

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Investigating the functional roles of CTSH and PGM1 in beta-cells during autoimmune diabetes development - Project Summary / Abstract This K01 award will allow Dr. Yi (Jody) Ye-Miller to advance her independent research career in the field of type 1 diabetes (T1D). Dr. Ye’s overarching career goal is to understand the pathogenic mechanisms behind the genetic and environmental influence of pancreatic beta-cells in T1D and to identify targeted pathways to improve beta-cell function. The proposed project is carefully conceived, based on Dr.Ye’s previous work and trains her to use novel models as well as cutting-edge technologies to study the mechanisms underlying T1D. It is a timely opportunity and excellent training vehicle to enable an extremely talented young scientist to achieve her career independence. The Albert Einstein College of Medicine is a national leader in medical education, research, and health care. The institution and Dr. Ye’s mentors will provide a supportive environment with all the necessary equipment and facilities, as well as many learning opportunities and guidance for her professional development. T1D affects 5% of the U.S. population with increasing prevalence in recent decades, especially among young children. Current therapies are unable to provide long-lasting effects to improve beta cell function. The etiology of T1D has both genetic and environmental components, but our understanding of the underlying mechanisms is incomplete, hindering the development of novel therapies. In Dr. Ye’s previous postdoctoral trainings, she identified two T1D loci, CTSH and PGM1, which showed evidence of genetic and environmental influence. Both CTSH and PGM1 are expressed in pancreatic beta-cells. Her observations led to the hypothesis that genetic and/or environment factors influence CTSH and PGM1 transcription and translation, which alter the function and stress-response of beta-cells that consequently trigger T1D. In this project, Dr. Ye will use CRISPR-Cas9 technology to modify the expression of CTSH and PGM1 in human embryonic stem cells. Edited stem cells will subsequently be differentiated into pancreatic beta-cells in vitro. Dr. Ye will investigate the effect of CTSH and PGM1 on beta-cell function with and without an environmental stimulus such as viral infection. In addition, Dr. Ye will use a transgenic mouse model to investigate whether CTSH or its related pathways can be targeted to prevent or slow autoimmune diabetes development. CTSH and PGM1 are T1D associated genes, but their beta-cells specific effects have not been thoroughly studied. The proposed experiments are innovative and original. In a short term, funding will allow Dr. Ye to establish her career independence in the field of T1D. In a long run, these studies will unravel the pathogenic mechanisms associated with CTSH and PGM1 loci, allowing the development of new therapies to treat T1D in humans.


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 = $153,360 )
2025	2025	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	4	2/14/2025	NON-COMPETING CONTINUATION	$153,360
														Subtotal = $153,360

Issue Date FY: 2024 ( Subtotal = $153,360 )
2024	2024	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	1/19/2024	NON-COMPETING CONTINUATION	$153,360
														Subtotal = $153,360

Issue Date FY: 2023 ( Subtotal = $153,360 )
2023	2023	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	1/6/2023	NON-COMPETING CONTINUATION	$153,360
														Subtotal = $153,360

Issue Date FY: 2022 ( Subtotal = $154,860 )
2022	2022	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	2/1/2022	NEW	$154,860
														Subtotal = $154,860

Grand Total All Awards = $614,940

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Investigating the functional roles of CTSH and PGM1 in beta-cells during autoimmune diabetes development

Award Number: K01DK131329

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 02/01/2022

PERIOD OF PERFORMANCE END DATE: 01/31/2027

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