Tracy Young-Pearse, Ph.D.
Title Associate Professor of Neurology Institution Brigham and Women's Hospital Address Brigham and Women's Neurology/HBTM 10010O 60 Fenwood Rd Boston MA 02115
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Overview
Young-Pearse lab website:
http://youngpearselab.bwh.harvard.edu/Young-Pearse_Lab/home.html

Mentoring
Available: 01/10/22, Expires: 01/01/27
A central question in Alzheimers Disease (AD) is the role of cell type-specific changes associated with the onset and progression of the disease. Genome-wide association studies have identified genes linked to AD, and recent large-scale transcriptomic and proteomic studies of post-mortem brain tissue have highlighted candidate genes and proteins with significant associations to pathological and clinical manifestations of AD. Together, these genetic and molecular studies have implicated neurons, astrocytes, and microglia as key players in AD pathogenesis and cognitive decline. However, these genetic and post-mortem profiling studies cannot resolve the degree to which a change in cell type expression profile is cell autonomous, as opposed to being a downstream effect of changes in other cell types. To tackle this question, we propose an innovative mixed in vitro co-culture approach to understand the effects of cell types from donors with variations in AD pathology and or AD dementia on cell types derived from individuals with or without cognitive decline or pathology. We use induced pluripotent stem cell (iPSC) lines from members of the Religious Order Study/Memory and Aging Project (ROSMAP), for whom we have detailed pathological, clinical, whole- genome sequencing, and post-mortem molecular data. This allows us to anchor our in vitro findings directly to patient phenotypes and analyses of post-mortem brain tissue data. Based on this anchoring, our approach is to mix and match cell type-specific cultures from different iPSC lines, thereby allowing us to disentangle which cell type-specific changes in vitro are likely cell type autonomous, and which are induced non- autonomously by cells from a donor with a different genetic background, pathology, and ante-mortem cognitive trajectory. Importantly, we look for conserved, polygenic AD-associated signals in vitro that are present across donors with varied genetic backgrounds, as opposed to directly characterizing the effect of a specific variant on cell type. Given the highly multifactorial nature of AD genetic risk variants, we believe this approach allows for robust identification of convergent cell type-specific effects associated with the disease. Students may be involved with either the "wet lab" generation of data, the "dry lab" analysis of data, or a combination of both. The specific goals of the individual's project will depend upon the status of the overarching project on the start date.

Research
The research activities and funding listed below are automatically derived from
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RF1NS117446
(YOUNG-PEARSE, TRACY L)
Sep 15, 2020 - Aug 31, 2024
Cell and Molecular Consequences of Alzheimer's Disease Genetic Variants on BBB Integrity and Function
Role: Principal Investigator
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R21MH118576
(YOUNG-PEARSE, TRACY L)
Apr 1, 2019 - Feb 28, 2021
Establishing a human cellular model of sex differences in the brain
Role: Principal Investigator
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R01AG055909
(YOUNG-PEARSE, TRACY L)
Jul 15, 2018 - Apr 30, 2023
Probing Heterogeneity of Alzheimer's disease using iPSCs
Role: Principal Investigator
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RF1AG057457
(CHANG, RUI)
Sep 15, 2017 - Aug 31, 2021
Building Novel Predictive Networks for high-throughput, in-silico Key Driver Prioritization to Enhance Drug Target Discovery in AMP-AD and M2OVE-AD
Role: Co-Principal Investigator
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R21AG056011
(YOUNG-PEARSE, TRACY L)
Apr 1, 2017 - Mar 31, 2019
Feasibility of studying vulnerability versus protection to high amyloid load using iPSCs
Role: Principal Investigator
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R21AG053827
(YOUNG-PEARSE, TRACY L)
Aug 1, 2016 - May 31, 2018
Altered APP metabolism triggers changes in tau that cause dementia
Role: Principal Investigator
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R33AG049864
(YOUNG-PEARSE, TRACY L)
Sep 30, 2014 - Mar 31, 2018
Detection of cell type specific effects of pathway manipulation in neural cells
Role: Principal Investigator
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R01MH101148
(YOUNG-PEARSE, TRACY L)
May 1, 2014 - Feb 29, 2020
Genes and developmental signaling pathways in neuropsychiatric disorders
Role: Principal Investigator
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RF1AG042776
(YOUNG-PEARSE, TRACY L)
Sep 1, 2012 - Aug 31, 2014
Analyses of AD relevant phenotypes in neural cells derived from human iPSCs
Role: Principal Investigator
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S10OD010589
(YOUNG-PEARSE, TRACY L)
Jun 1, 2012 - May 31, 2013
Confocal Microscope for the Study of Neurologic Diseases
Role: Principal Investigator
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R21MH096233
(YOUNG-PEARSE, TRACY L)
Apr 1, 2012 - Mar 31, 2015
Profiling of cortical cells by microengraving and mass spectrometry imaging
Role: Principal Investigator
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R00MH085004
(YOUNG-PEARSE, TRACY L)
Jun 1, 2009 - May 31, 2015
Functions of DISC1 and APP in Cortical Development and Neuropsychiatric Disorders
Role: Principal Investigator
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K99MH085004
(YOUNG-PEARSE, TRACY L)
Jun 1, 2009 - May 31, 2011
Functions of DISC1 and APP in Cortical Development and Neuropsychiatric Disorders
Role: Principal Investigator
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F32NS053320
(YOUNG-PEARSE, TRACY L)
Jun 1, 2006 - May 31, 2009
Functions of APP Family Members in Neuronal Development
Role: Principal Investigator

Bibliographic
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