Thursday, July 3, 2025 7/3/2025

Single-cell multi-region dissection of AD-pathogen interactions for HSV-1 and CMV

Award Number: R01AG081017
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 02/01/2023
PERIOD OF PERFORMANCE END DATE: 01/31/2028

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Single-cell multi-region dissection of AD-pathogen interactions for HSV-1 and CMV - Abstract Alzheimer’s disease (AD) is a neurodegenerative disorder that leads to dramatic effects on the affected individuals and their families. While the characterization of the genetic contribution to AD and underlying molecular mechanisms has advanced the understanding of the disease in recent years, studies have failed to find definitive mechanisms that account for disease progression. The influence of pathogens on AD potentially mediates an environmental impact on the established genetic contributions to AD. Here, we directly dissect the contribution of pathogen-related effects down to the cell-type-specific molecular basis by systematic profiling, computational integration, and experimental validation of the transcriptional signatures across individuals, brain regions, and cell types. In Aim 1, we use scRNA-seq in human, mouse, and human iPSC brain organoid samples of AD that are infected with Herpes Simplex Virus 1 or Cytomegalovirus (HSV-1/CMV) to generate millions of single- cell (sc) level maps with the end goal of a transcriptional atlas. In Aim 2, we analyze the resulting datasets and underlying molecular mechanisms, enabling us to discover and converge genes, pathways, cell types, and brain regions to functional and causal mechanisms that drive pathogen-related alterations. In Aim 3, we use our well-established iPSC model to test our predicted mechanisms with both high-throughput and cell-type specific assays. The resulting datasets, computational predictions, and experimentally-supported mechanisms will shed light on the pathogen-related influences on AD pathology and will help deepen our understanding of the disease in general as we develop more personalized therapeutic approaches to treating AD.


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 = $727,847 )
2025	2025	MASSACHUSETTS INSTITUTE OF TECHNOLOGY	77 MASSACHUSETTS AVE	CAMBRIDGE	MA	02139	MIDDLESEX	USA	Aging Research	001	3	6/13/2025	NON-COMPETING CONTINUATION	$59,417
2025	2025	MASSACHUSETTS INSTITUTE OF TECHNOLOGY	77 MASSACHUSETTS AVE	CAMBRIDGE	MA	02139	MIDDLESEX	USA	Aging Research	000	3	3/4/2025	NON-COMPETING CONTINUATION	$668,430
														Subtotal = $727,847

Issue Date FY: 2024 ( Subtotal = $752,834 )
2024	2024	MASSACHUSETTS INSTITUTE OF TECHNOLOGY	77 MASSACHUSETTS AVE	CAMBRIDGE	MA	02139	MIDDLESEX	USA	Aging Research	001	2	6/10/2024	NON-COMPETING CONTINUATION	$75,283
2024	2024	MASSACHUSETTS INSTITUTE OF TECHNOLOGY	77 MASSACHUSETTS AVE	CAMBRIDGE	MA	02139	MIDDLESEX	USA	Aging Research	000	2	1/19/2024	NON-COMPETING CONTINUATION	$677,551
														Subtotal = $752,834

Issue Date FY: 2023 ( Subtotal = $786,088 )
2023	2023	MASSACHUSETTS INSTITUTE OF TECHNOLOGY	77 MASSACHUSETTS AVE	CAMBRIDGE	MA	02139	MIDDLESEX	USA	Aging Research	000	1	1/31/2023	NEW	$786,088
														Subtotal = $786,088

Grand Total All Awards = $2,266,769

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Single-cell multi-region dissection of AD-pathogen interactions for HSV-1 and CMV

Award Number: R01AG081017

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 02/01/2023

PERIOD OF PERFORMANCE END DATE: 01/31/2028

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