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The role of mitochondrial regulation in cell lineage specification and function

Award Number: R35GM147713
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/01/2022
PERIOD OF PERFORMANCE END DATE: 06/30/2027

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The role of mitochondrial regulation in cell lineage specification and function - ABSTRACT The role of mitochondrial regulation in cell lineage specification and function During cell lineage specification, metabolic reprogramming, together with transcriptional and epigenetic modifications in the progenitor cells are integral parts of cellular adaptations to the cell fate instructive cues. When this process goes awry, developmental defects as well as malignancies will occur. Common in all the cellular systems, mitochondria are bioenergetic, biosynthetic and signaling organelles central to metabolic remodeling. Understanding mechanisms of mitochondrial function during lineage specification will be critical for therapeutic normalization of derailed cellular metabolism and functions in pathogenesis. Though mitochondrial regulation is still unclear, our published and preliminary work revealed critical roles of mitochondrial metabolism and mitochondrial dynamics during cell lineage specification. Furthermore, differentiated cells continue to receive low-level, constitutive signaling in the basal state (“tonic signals”), important for cell survival or functions. Our research suggested that mitochondrial regulation is actively maintained in mature differentiated cells downstream of tonic signals and revealed potential new regulators for this process. The overarching theme of our research is to unravel the diverse mitochondria mediated mechanisms regulating cell lineage differentiation and homeostatic functions. In Project 1, we will use high resolution imaging to characterize distinct mitochondrial morphology, and dynamic events in live cells. Using genetic tools, and an organ culture system to model cell lineage specification, we will decipher the role of mitochondrial dynamics in metabolic remodeling during differentiation. In Project 2, using a sophisticated system of transferring cells into environments with defined levels of tonic signals, we will assess the alterations in mitochondrial dynamics and functions in the presence and absence of tonic signals. Through pharmacological means or genetic modifications such as CRISPR/Ca9 in differentiated cells, we will determine the causal relationship between mitochondrial regulation and maintenance of cellular functions. Upon completion of our work, we will have uncovered the versatile mechanisms by which mitochondria influence lineage specification and homeostatic functions.


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 = $426,250 )
2025	2025	OKLAHOMA MEDICAL RESEARCH FOUNDATION	825 NE 13TH ST	OKLAHOMA CITY	OK	73104	OKLAHOMA	USA	Biomedical Research and Research Training	000	4	6/17/2025	NON-COMPETING CONTINUATION	$426,250
														Subtotal = $426,250

Issue Date FY: 2024 ( Subtotal = $432,107 )
2024	2024	OKLAHOMA MEDICAL RESEARCH FOUNDATION	825 NE 13TH ST	OKLAHOMA CITY	OK	73104	OKLAHOMA	USA	Biomedical Research and Research Training	000	3	6/21/2024	NON-COMPETING CONTINUATION	$426,250
2024	2024	OKLAHOMA MEDICAL RESEARCH FOUNDATION	825 NE 13TH ST	OKLAHOMA CITY	OK	73104	OKLAHOMA	USA	Biomedical Research and Research Training	001	3	6/22/2024	SUPPLEMENT FOR EXPANSION	$5,857
														Subtotal = $432,107

Issue Date FY: 2023 ( Subtotal = $558,568 )
2023	2023	OKLAHOMA MEDICAL RESEARCH FOUNDATION	825 NE 13TH ST	OKLAHOMA CITY	OK	73104	OKLAHOMA	USA	Biomedical Research and Research Training	001	2	5/31/2023	NON-COMPETING CONTINUATION	$426,250
2023	2023	OKLAHOMA MEDICAL RESEARCH FOUNDATION	825 NE 13TH ST	OKLAHOMA CITY	OK	73104	OKLAHOMA	USA	Biomedical Research and Research Training	000	1	5/24/2023	SUPPLEMENT FOR EXPANSION	$67,895
2023	2023	OKLAHOMA MEDICAL RESEARCH FOUNDATION	825 NE 13TH ST	OKLAHOMA CITY	OK	73104	OKLAHOMA	USA	Biomedical Research and Research Training	002	2	8/7/2023	SUPPLEMENT FOR EXPANSION	$64,423
														Subtotal = $558,568

Issue Date FY: 2022 ( Subtotal = $426,250 )
2022	2022	OKLAHOMA MEDICAL RESEARCH FOUNDATION	825 NE 13TH ST	OKLAHOMA CITY	OK	73104	OKLAHOMA	USA	Biomedical Research and Research Training	000	1	8/26/2022	NEW	$426,250
														Subtotal = $426,250

Grand Total All Awards = $1,843,175

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The role of mitochondrial regulation in cell lineage specification and function

Award Number: R35GM147713

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/01/2022

PERIOD OF PERFORMANCE END DATE: 06/30/2027

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