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Prognostic implications of mitochondrial inheritance in myelodysplastic syndromes after stem-cell transplantation

Award Number: K01HL164972
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 04/20/2023
PERIOD OF PERFORMANCE END DATE: 03/31/2028

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Prognostic implications of mitochondrial inheritance in myelodysplastic syndromes after stem-cell transplantation - ABSTRACT Myelodysplastic syndromes (MDS) are a heterogenous group of clonal hematopoietic stem cell disorders, characterized by ineffective hematopoiesis and a tendency to progress to acute myeloid leukemia in 30% of the patients. Currently the only curative therapy for MDS is allogeneic hematopoietic stem-cell transplantation (HCT). However, the mortality after HCT is high due to relapsed disease and transplant-related complications. The commonly used MDS prognostic models for HCT only consider non-genetic factors, thus could not accurately predict the outcomes after HCT. Novel predictive markers are therefore critically needed to identify patients who are most likely to benefit from HCT. Mitochondria play a critical role in hematopoietic cell homeostasis and differentiation. Genetic and epigenetic alterations in mitochondrial DNA (mtDNA) can impair mitochondrial functions and play a pathophysiological role in MDS. This Career Development Award will provide training and research experience to Dr. Dong to support her long-term career goal of becoming an independent investigator in integrative molecular epidemiology, with a focus on applying state-of-the-art omics technologies and innovative population-based epidemiologic methods to reduce the burden of hematologic diseases. While Dr. Dong has had comprehensive training in genetics and epidemiology, she requires further training in methodologies of HCT-related outcomes and epigenetics. She has assembled a mentoring team comprised of a primary mentor, Dr. Raul Urrutia, Director in the Genomic Sciences and Precision Medicine Center and renowned leader in genomics, epigenomics and precise medicine; and two co-mentors: Dr. Wael Saber, Professor and Scientific Director in the Acute and Chronic Leukemia Working Committees in the CIBMTR specializing in HCT and MDS; Dr. Paul Auer, Professor and Cancer Center Core Director with expertise in statistics and bioinformatics. Leveraging the existing whole genome sequencing data from the “MDS Genomics and Epigenetics Study” in the CIBMTR, Dr. Dong will focus on mitochondrial genome to address the research gaps mentioned above: 1) determine mitochondrial genomic landscape associated with MDS outcomes after allo-HCT; 2) quantify mtDNA copy number and evaluate its associations with MDS outcomes after HCT; and 3) identify mtDNA methylation profiles associated with MDS outcomes after HCT. The findings will improve our understanding of MDS etiology and provide additional molecular predictors of MDS outcomes after HCT to help developing individualized risk prediction and targeted treatments.


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 = $156,600 )
2025	2025	THE MEDICAL COLLEGE OF WISCONSIN, INC.	8701 WATERTOWN PLANK RD	MILWAUKEE	WI	53226	MILWAUKEE	USA	Blood Diseases and Resources Research	000	3	3/25/2025	NON-COMPETING CONTINUATION	$156,600
														Subtotal = $156,600

Issue Date FY: 2024 ( Subtotal = $156,600 )
2024	2024	THE MEDICAL COLLEGE OF WISCONSIN, INC.	8701 WATERTOWN PLANK RD	MILWAUKEE	WI	53226	MILWAUKEE	USA	Blood Diseases and Resources Research	000	2	3/27/2024	NON-COMPETING CONTINUATION	$156,600
														Subtotal = $156,600

Issue Date FY: 2023 ( Subtotal = $156,600 )
2023	2023	THE MEDICAL COLLEGE OF WISCONSIN, INC.	8701 WATERTOWN PLANK RD	MILWAUKEE	WI	53226	MILWAUKEE	USA	Blood Diseases and Resources Research	000	1	4/19/2023	NEW	$156,600
														Subtotal = $156,600

Grand Total All Awards = $469,800

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Prognostic implications of mitochondrial inheritance in myelodysplastic syndromes after stem-cell transplantation

Award Number: K01HL164972

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 04/20/2023

PERIOD OF PERFORMANCE END DATE: 03/31/2028

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