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WIPI2B/ATG-18 phosphorylation regulates neuronal autophagosome biogenesis in vivo

Award Number: F31AG086033
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 01/08/2025
PERIOD OF PERFORMANCE END DATE: 01/07/2028

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WIPI2B/ATG-18 phosphorylation regulates neuronal autophagosome biogenesis in vivo - PROJECT SUMMARY Autophagy is a homeostatic mechanism that cells utilize to clear waste. Autophagy is especially important for neurons because they cannot dilute waste through cell division. However, the rate of neuronal autophagy decreases during aging, and the misregulation of autophagy has been implicated in many age-related neurodegenerative diseases (NDDs) including Alzheimer’s Disease and Related Dementias (ADRD). We previously found that the decrease in autophagy seen in aged primary neurons can be rescued through the overexpression of WIPI2B, a key autophagy component. Moreover, the phosphorylation state of WIPI2B dictates its ability to restore autophagy in aged neurons. Based on these data, I hypothesize that the phosphorylation state of WIPI2B regulates its function in neuronal autophagy and that increasing levels of dephosphorylated WIPI2B upregulates neuronal autophagy. Overall, this proposal aims to investigate the mechanisms of neuronal autophagy regulation in vivo (Aims 1 and 2) and apply this in a NDD context using a C. elegans model of AD (Aim 3). A better understanding of how neurons utilize and regulate autophagy will uncover novel therapeutic targets for treating NDDs. The Stavoe lab at UTHealth Houston is the ideal environment for me to conduct this research and complete my graduate training. In addition to performing the experiments outlined in the research plan, I will develop my technical, critical thinking, and communication skills through in-class instruction, mentorship in the lab, and attendance of seminars and conferences. As my graduate institution is located in the largest medical center in the world, I have access to classes, workshops, and seminars held by the different institutions, and I have the opportunity to network and discuss science with experts across a broad range of topics. Altogether, the proposed project and my training plan will impact our understanding of neuronal autophagy regulation and prepare me for my future research career in neurobiology.


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 = $38,100 )
2026	2026	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON	7000 FANNIN ST FL 9	HOUSTON	TX	77030	HARRIS	USA	Aging Research	001	2	3/24/2026	NON-COMPETING CONTINUATION	$576
2026	2026	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON	7000 FANNIN ST FL 9	HOUSTON	TX	77030	HARRIS	USA	Aging Research	000	2	1/21/2026	NON-COMPETING CONTINUATION	$37,524
														Subtotal = $38,100

Issue Date FY: 2024 ( Subtotal = $36,960 )
2024	2024	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON	7000 FANNIN ST FL 9	HOUSTON	TX	77030	HARRIS	USA	Aging Research	000	1	7/8/2024	NEW	$36,960
														Subtotal = $36,960

Grand Total All Awards = $75,060

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WIPI2B/ATG-18 phosphorylation regulates neuronal autophagosome biogenesis in vivo

Award Number: F31AG086033

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 01/08/2025

PERIOD OF PERFORMANCE END DATE: 01/07/2028

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