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Characterizing Myeloid Nuclear Differentiation Antigen (MNDA) in Alzheimer's Disease

Award Number: F31AG099446
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 09/01/2026
PERIOD OF PERFORMANCE END DATE: 08/31/2029

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Characterizing Myeloid Nuclear Differentiation Antigen (MNDA) in Alzheimer's Disease - PROJECT SUMMARY Alzheimer’s Disease (AD) is a chronic, progressive neurodegenerative disorder of the central nervous system (CNS) that leads to cognitive impairment and remains a significant global health challenge among the aging population. Despite advancements in therapeutics, the cellular mechanisms underlying AD—particularly the neuronal phenotypes of the CNS and their complex intracellular functions—are not fully understood. Our lab specializes in characterizing tRNA-derived RNA fragments (tRFs), a recently discovered class of small non- coding RNAs (sncRNAs), and their roles in neurodegenerative diseases. We previously reported that tRFs represent the most abundant sncRNA population in the hippocampus of AD patients. These AD-affected tRFs originate from a limited subset of mature tRNAs, with some showing functional correlations to disease severity. Among these, a tRF derived from the 5’-end of the tRNA encoding GlyCCC (tRF5-GlyCCC) has emerged as a key molecule of interest. Of surveyed AD patients by our lab, human serum samples provided a differentially expressed gene candidate that possibly contributes to dysregulated neuron function in AD. Preliminary data show that AD patients exhibit significantly elevated myeloid nuclear differentiation antigen (MNDA) levels in their serum, hippocampal tissues, and iPSC-derived neurons. Furthermore, our computational target prediction algorithms and experimental data suggest that MNDA is a potential target of tRF5-GlyCCC. The long-term goal of this project is to investigate the biological and health consequences of AD-affected tRFs to deepen our understanding of disease mechanisms. The objective of this grant is to determine how dysregulated MNDA impacts neuronal function and how this gene is regulated by AD-specific tRFs. We hypothesize that MNDA is a disease-associated gene in AD and that tRF5-GlyCCC contributes to its expression and regulation. In Aim 1, the effects of MNDA on neuronal cell phenotypes in AD will be investigated. In Aim 2, the regulatory interaction between tRF5-GlyCCC and MNDA will be characterized. Through this F31 fellowship, the conclusion of MNDA’s function and regulation by tRFs would provide novel mechanistic insights into AD progression, particularly in diverse patient populations with sporadic forms of the disease. Additionally, I will acquire advanced skills in cell culture and molecular biology, including iPSC culture, cell differentiation/maturation, CRISPR/Cas9 gene editing, and various assays to evaluate neuronal phenotypes specific to AD. These methodologies will be standardized into protocols, contributing to both our lab and the broader fields of AD research and sncRNA biology. These experiences will prepare me for my long-term career goal of becoming an independent molecular and neuroinflammatory research scientist.


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 = $39,532 )
2026	2026	UNIVERSITY OF TEXAS MEDICAL BRANCH AT GALVESTON	301 UNIVERSITY BLVD	GALVESTON	TX	77555	GALVESTON	USA	Aging Research	001	1	6/16/2026	NEW	$0
2026	2026	UNIVERSITY OF TEXAS MEDICAL BRANCH AT GALVESTON	301 UNIVERSITY BLVD	GALVESTON	TX	77555	GALVESTON	USA	Aging Research	000	1	6/16/2026	NEW	$39,532
														Subtotal = $39,532

Grand Total All Awards = $39,532

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Characterizing Myeloid Nuclear Differentiation Antigen (MNDA) in Alzheimer's Disease

Award Number: F31AG099446

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 09/01/2026

PERIOD OF PERFORMANCE END DATE: 08/31/2029

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