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Molecular Regulators of Mitochondrial Dynamics in the Progression of Secondary Injury Following Trauma

Award Number: F31NS147419
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 03/01/2026
PERIOD OF PERFORMANCE END DATE: 02/28/2029

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Molecular Regulators of Mitochondrial Dynamics in the Progression of Secondary Injury Following Trauma - PROJECT SUMMARY Traumatic brain injury (TBI) affects 1.7 million Americans each year and is the leading cause of disability worldwide. TBI is defined as having two distinct pathophysiological phases: the primary injury, or initial impact, leads to a secondary injury cascade that lasts minutes to years later defined by an energy deficit and ionic imbalance in cells that contribute to neuronal death. Mitochondria play a large role in maintaining cellular homeostasis and meeting energetic requirements of neurons, making their dysfunction integral to the pathophysiology of secondary injury. Central to the health of the mitochondria, and therefore to the cell, is the tight regulation of coordinated cycles of fission and fusion, known as dynamics. Imbalance between these states leads to an altered electrochemical gradient and membrane potential, which reduces energetic efficiency, and resembles the hallmarks of the TBI secondary cascade. My hypothesis is that the disruption of key molecular regulators of mitochondrial dynamics plays a causal role in the progression of secondary injury following trauma. To test this, I will 1: establish the extent and timing of mitochondrial morphologic disruption after in vitro primary neuron axon stretch injury (ASI) using super-resolution live-cell microscopy with Ca2+, ROS, and ΔΨm fluorescent probes paired with the machine learning mitochondrial morphology classifier developed in the Sanderson lab. I will then gain insight into the activation and influence of fission and fusion regulatory proteins after ASI using novel gain- and loss- of function primary neurons from the lab’s transgenic conditional knockouts of Drp1 and Oma1, which mediate fission and inhibit fusion, respectively. Furthermore, I will 2: interrogate the role of mitochondrial dynamic regulatory proteins in the progression of secondary injury using the controlled cortical impact (CCI) mouse model paired with the Drp1 and Oma1 conditional knockout transgenic mice. Behavioral deficits and lesion size will be measured to confirm injury, and cutting-edge biochemical and imaging techniques, including whole slice immunofluorescence and mitochondrial segmentation of key brain regions, will be used to measure changes in pathology. Collectively, this research will provide crucial insight into the molecular underpinnings of mitochondrial dysfunction after brain trauma, potentially providing a route of therapeutic development to reduce cell death during the progression of the secondary injury.


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: 2026 ( Subtotal = $43,714 )
2026	2026	REGENTS OF THE UNIVERSITY OF MICHIGAN	1109 GEDDES AVE STE 3300	ANN ARBOR	MI	48109	WASHTENAW	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	2/13/2026	NEW	$43,138
2026	2026	REGENTS OF THE UNIVERSITY OF MICHIGAN	1109 GEDDES AVE STE 3300	ANN ARBOR	MI	48109	WASHTENAW	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	1	2/13/2026	NEW	$0
2026	2026	REGENTS OF THE UNIVERSITY OF MICHIGAN	1109 GEDDES AVE STE 3300	ANN ARBOR	MI	48109	WASHTENAW	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	1	4/15/2026	NEW	$576
														Subtotal = $43,714

Grand Total All Awards = $43,714

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Molecular Regulators of Mitochondrial Dynamics in the Progression of Secondary Injury Following Trauma

Award Number: F31NS147419

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 03/01/2026

PERIOD OF PERFORMANCE END DATE: 02/28/2029

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