Tuesday, April 23, 2024 4/23/2024

Loss of nuclear integrity is sufficient to induce age-associated changes and Alzheimer's pathology in hPSC-derived cortical neurons.

Award Number: F31AG067709
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

Group Awards By Issue Date FY or Funding FY:

View Award Abstract

Project Abstract: Alzheimer’s Disease (AD) is the most common neurodegenerative disease in the United States affecting an estimated 5.4 million patients 48. To date, there are no effective cures and limited therapies available for patients 49. While a small number of AD cases are linked to genetic mutations in Amyloid Precursor Protein processing, the genetic basis of most AD cases remains poorly understood 50. Induce Pluripotent Stem Cells (iPSCs) provide a unique opportunity to study the genetics of AD, by providing an unlimited supply of disease- relevant tissue while retaining the genetic background of their somatic cell donor 51. Studies have shown the process of iPSC reprogramming resets the age of patient iPSCs 5. Consequently, cells derived from iPSCs tend to yield immature and prenatal cell types, presenting a major hurdle for late-onset disease modelling 5, 6. Induced aging protocols are a novel strategy for accelerating age in iPSC-derived cells for modelling late-stage degenerative disease phenotypes 5,6. While these protocols have been established for generating iPSC-based models of Parkinson’s Disease, they have yet to be applied to AD. There are numerous studies which describe a decline in multiple aspects of nuclear homeostasis that occur with age and in AD patient brains, including differential expression of lamin proteins, a shift in nuclear-cytoplasmic transport activity, and a decline in nucleoporin and transport proteins 8-10, 22, 24, 25, 35-38. It is therefore plausible that a loss of nuclear integrity is sufficient to induce age-related and pathological changes associated with AD in hPSC-derived cortical neurons. The proposed research project aims to use genetic strategies to mimic age-associated changes within the nucleus to determine if nuclear perturbation is sufficient to drive other aspects of cellular age and potentiate AD pathology. These studies could create an innovative age-implicated model of AD, develop novel methods for modelling late-onset diseases in other cell types, and provide new insights into drivers of cellular and nuclear aging.


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: 2024 ( Subtotal = $0 )
2024	2022	WEILL MEDICAL COLLEGE OF CORNELL UNIVERSITY	575 LEXINGTON AVE FL 9	NEW YORK	NY	10022	NEW YORK	USA	Aging Research	000	3	3/22/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $46,752 )
2022	2022	WEILL MEDICAL COLLEGE OF CORNELL UNIVERSITY	1300 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Aging Research	000	3	5/11/2022	NON-COMPETING CONTINUATION	$46,753
2022	2022	WEILL MEDICAL COLLEGE OF CORNELL UNIVERSITY	1300 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Aging Research	001	3	7/1/2022	NON-COMPETING CONTINUATION	-$1
														Subtotal = $46,752

Issue Date FY: 2021 ( Subtotal = $46,036 )
2021	2021	WEILL MEDICAL COLLEGE OF CORNELL UNIVERSITY	1300 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Aging Research	000	2	5/13/2021	NON-COMPETING CONTINUATION	$46,036
														Subtotal = $46,036

Issue Date FY: 2020 ( Subtotal = $45,520 )
2020	2020	WEILL MEDICAL COLLEGE OF CORNELL UNIVERSITY	407 E 61ST ST RM 106 1ST FL	NEW YORK	NY	10065	NEW YORK	USA	Aging Research	000	1	5/13/2020	NEW	$45,520
														Subtotal = $45,520

Grand Total All Awards = $138,308

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Loss of nuclear integrity is sufficient to induce age-associated changes and Alzheimer's pathology in hPSC-derived cortical neurons.

Award Number: F31AG067709

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer