Friday, November 21, 2025 11/21/2025

Control of CNS Myelination by the E3 Ligase Component Fbxw7

Award Number: F31NS122433
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: 12/01/2021
PERIOD OF PERFORMANCE END DATE: 11/30/2024

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Control of CNS Myelination by the E3 Ligase Component Fbxw7 - PROJECT SUMMARY Myelination in the vertebrate central nervous system (CNS) is an evolutionarily conserved process where oligodendrocytes (OLs), a glial cell type within the CNS, wrap surrounding axons in membrane sheaths providing vital trophic support and insulation. This incredibly complex and dynamic process of myelination occurs throughout life, both in response to injury and as a continuous refinement of circuit dynamics. A previous forward genetic screen in zebrafish, aimed at identifying novel regulators of myelination, identified Fbwx7 as a negative regulator of CNS myelination. Fbxw7 is a recognition subunit of the SKP1-Cullin-Fbox (SCF) ubiquitin ligase complex. Loss of Fbxw7 resulted in a significant increase in myelin basic protein (mbp) expression, the number of OL lineage cells, and an increase in the number of myelinated axons and myelin wraps in the dorsal spinal cord of zebrafish. Additionally, loss of Fbxw7 in mature myelinating OLs in the mouse optic nerve resulted in a significant increase in the density of abnormally thick myelinated axons, myelin outfoldings, and degenerating axons, showing for the first time a role for Fbxw7 in regulating myelin homeostasis in the mammalian CNS. To determine the substrates that Fbxw7 might be regulating to control CNS myelination, I silenced Fbxw7 in primary OL cultures, and found a significant increase in the levels of the transcription factor Myelin Regulator Factor (Myrf), a key protein essential for myelination, and many novel proteins. I hypothesize that Fbxw7 controls CNS myelination by degrading protein substrates that regulate OPC proliferation, differentiation, and/or OL sheath length and myelin thickness. To investigate this, I will 1) examine OL development and dynamics in Fbxw7 loss of function zebrafish mutants and in OL lineage specific Cre mouse models, and 2) determine Fbxw7 substrates that regulate OL development and myelination using zebrafish genetics and rodent culture models. By combining these approaches, I will receive training in a diverse array of experimental methods and model systems, providing me with skills and options to pursue a successful career in science. Additionally, my co-appointment in Dr. Ben Emery’s (Jungers Center for Neuroscience Research) and Dr. Kelly Monk’s (Vollum institute) laboratories will provide me with institutional support from two exemplary departments and access to a large group of diverse PIs and trainees to aid in my scientific growth and training.


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 = $0 )
2025	2024	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	9/26/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $48,974 )
2024	2024	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	3	5/9/2024	NON-COMPETING CONTINUATION	$1,280
2024	2024	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	11/9/2023	NON-COMPETING CONTINUATION	$47,694
														Subtotal = $48,974

Issue Date FY: 2023 ( Subtotal = $47,694 )
2023	2023	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	2	2/9/2023	NON-COMPETING CONTINUATION	$942
2023	2023	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	12/1/2022	NON-COMPETING CONTINUATION	$46,752
														Subtotal = $47,694

Issue Date FY: 2022 ( Subtotal = $46,752 )
2022	2022	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	11/22/2021	NEW	$46,036
2022	2022	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	1	11/22/2021	NEW	$0
2022	2022	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	1	6/23/2022	NEW	$716
														Subtotal = $46,752

Grand Total All Awards = $143,420

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Control of CNS Myelination by the E3 Ligase Component Fbxw7

Award Number: F31NS122433

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: 12/01/2021

PERIOD OF PERFORMANCE END DATE: 11/30/2024

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