Philip L. De Jager
Columbia University in the City of New York
H-index: 133
North America-United States
Description
Philip L. De Jager, With an exceptional h-index of 133 and a recent h-index of 101 (since 2020), a distinguished researcher at Columbia University in the City of New York, specializes in the field of genetics, immunology, multiple sclerosis, Alzheimer, systems biology.
His recent articles reflect a diverse array of research interests and contributions to the field:
Multi-omics and pathway analyses of genome-wide associations implicate regulation and immunity in verbal declarative memory performance
Bridging the Gap: Multi-Omics Profiling of Brain Tissue in Alzheimer's Disease and Older Controls in Multi-Ethnic Populations
Associations of Brain Morphology with Cortical Proteins of Cognitive Resilience
Association of whole-person eigen-polygenic risk scores with Alzheimer’s disease
Association of 10 VEGF Family Genes with Alzheimer's Disease Pathology at Single Cell Resolution
ZCCHC17 modulates neuronal RNA splicing and supports cognitive resilience in Alzheimer's disease
CHRNA5 links chandelier cells to severity of amyloid pathology in aging and Alzheimer’s disease
Post-COVID Conditions in People with Multiple Sclerosis: A Cross-sectional Multicenter Study (P1-6.002)
Professor Information
University | Columbia University in the City of New York |
---|---|
Position | Weil-Granat Professor of Neurology at |
Citations(all) | 94204 |
Citations(since 2020) | 55087 |
Cited By | 61235 |
hIndex(all) | 133 |
hIndex(since 2020) | 101 |
i10Index(all) | 456 |
i10Index(since 2020) | 412 |
University Profile Page | Columbia University in the City of New York |
Research & Interests List
genetics
immunology
multiple sclerosis
Alzheimer
systems biology
Top articles of Philip L. De Jager
Multi-omics and pathway analyses of genome-wide associations implicate regulation and immunity in verbal declarative memory performance
BackgroundUncovering the functional relevance underlying verbal declarative memory (VDM) genome-wide association study (GWAS) results may facilitate the development of interventions to reduce age-related memory decline and dementia.MethodsWe performed multi-omics and pathway enrichment analyses of paragraph (PAR-dr) and word list (WL-dr) delayed recall GWAS from 29,076 older non-demented individuals of European descent. We assessed the relationship between single-variant associations and expression quantitative trait loci (eQTLs) in 44 tissues and methylation quantitative trait loci (meQTLs) in the hippocampus. We determined the relationship between gene associations and transcript levels in 53 tissues, annotation as immune genes, and regulation by transcription factors (TFs) and microRNAs. To identify significant pathways, gene set enrichment was tested in each cohort and meta …
Authors
Hao Mei,Jeannette Simino,Lianna Li,Fan Jiang,Joshua C Bis,Gail Davies,W David Hill,Charley Xia,Vilmundur Gudnason,Qiong Yang,Jari Lahti,Jennifer A Smith,Mirna Kirin,Philip De Jager,Nicola J Armstrong,Mohsen Ghanbari,Ivana Kolcic,Christopher Moran,Alexander Teumer,Murali Sargurupremraj,Shamsed Mahmud,Myriam Fornage,Wei Zhao,Claudia L Satizabal,Ozren Polasek,Katri Räikkönen,David C Liewald,Georg Homuth,Michele Callisaya,Karen A Mather,B Gwen Windham,Tatijana Zemunik,Aarno Palotie,Alison Pattie,Sandra van der Auwera,Anbupalam Thalamuthu,David S Knopman,Igor Rudan,John M Starr,Katharina Wittfeld,Nicole A Kochan,Michael E Griswold,Veronique Vitart,Henry Brodaty,Rebecca Gottesman,Simon R Cox,Bruce M Psaty,Eric Boerwinkle,Daniel I Chasman,Francine Grodstein,Perminder S Sachdev,Velandai Srikanth,Caroline Hayward,James F Wilson,Johan G Eriksson,Sharon LR Kardia,Hans J Grabe,David A Bennett,M Arfan Ikram,Ian J Deary,Cornelia M van Duijn,Lenore Launer,Annette L Fitzpatrick,Sudha Seshadri,Jan Bressler,Stephanie Debette,Thomas H Mosley Jr
Journal
Alzheimer's Research & Therapy
Published Date
2024/1/20
Bridging the Gap: Multi-Omics Profiling of Brain Tissue in Alzheimer's Disease and Older Controls in Multi-Ethnic Populations
INTRODUCTION Multi-omics studies in Alzheimer's disease (AD) revealed many potential disease pathways and therapeutic targets. Despite their promise of precision medicine, these studies lacked African Americans (AA) and Latin Americans (LA), who are disproportionately affected by AD. METHODS To bridge this gap, Accelerating Medicines Partnership in AD (AMP-AD) expanded brain multi-omics profiling to multi-ethnic donors. RESULTS We generated multi-omics data and curated and harmonized phenotypic data from AA (n=306), LA (n=326), or AA and LA (n=4) brain donors plus Non-Hispanic White (n=252) and other (n=20) ethnic groups, to establish a foundational dataset enriched for AA and LA participants. This study describes the data available to the research community, including transcriptome from three brain regions, whole genome sequence, and proteome measures. DISCUSSION Inclusion of traditionally underrepresented groups in multi-omics studies is essential to discover the full spectrum of precision medicine targets that will be pertinent to all populations affected with AD.
Authors
Joseph S Reddy,Laura Heath,Abby Vander Linden,Mariet Allen,Katia de Pavia Lopes,Fatemeh Seifar,Erming Wang,Yiyi Ma,William Poehlman,Zachary S Quicksall,Alexi Runnels,Yanling Wang,Duc M Duong,Luming Yin,Kaiming Xu,Erica S Modeste,Anantharaman Shantaraman,Eric B Dammer,Lingyan Ping,Stephanie R Oatman,Jo Scanlan,Charlotte Ho,Minerva M Carrasquillo,Merve Atik,Geovanna Yepez,Adriana O Mitchell,Thuy T Nguyen,Xianfeng Chen,David X Marquez,Hasini Reddy,Harrison Xiao,Sudha Seshadri,Richard Mayeux,Stefan Prokop,Edward B Lee,Geidy E Serrano,Thomas G Beach,Andrew F Teich,Varham Haroutunian,Edward J Fox,Marla Gearing,Aliza Wingo,Thomas Wingo,James J Lah,Allan I Levey,Dennis W Dickson,Lisa L Barnes,Philip De Jager,Bin Zhang,David Bennett,Nicholas T Seyfried,Anna K Greenwood,Nilufer Ertekin-Taner
Journal
bioRxiv
Published Date
2024
Associations of Brain Morphology with Cortical Proteins of Cognitive Resilience
In a recent proteome-wide study, we identified several candidate proteins for drug discovery whose cortical abundance was associated with cognitive resilience to late-life brain pathologies. This study examines the extent to which these proteins are associated with the brain structures of cognitive resilience in decedents from the Religious Orders Study and Memory and Aging Project. Six proteins were associated with brain morphometric characteristics related to higher resilience (i.e., larger anterior and medial temporal lobe volumes), and five were associated with morphometric characteristics related to lower resilience (i.e., enlarged ventricles). Two synaptic proteins, RPH3A and CPLX1, remained inversely associated with the lower resilience signature, after further controlling for 10 neuropathologic indices. These findings suggest preserved brain structure in periventricular regions as a potential mechanism by …
Authors
Victoria N Poole,Abdur R Ridwan,Konstantinos Arfanakis,Robert J Dawe,Nicholas T Seyfried,Philip L De Jager,Julie A Schneider,Sue E Leurgans,Lei Yu,David A Bennett
Journal
Neurobiology of Aging
Published Date
2024/2/15
Association of whole-person eigen-polygenic risk scores with Alzheimer’s disease
Late-Onset Alzheimer’s Disease (LOAD) is a heterogeneous neurodegenerative disorder with complex etiology and high heritability. Its multifactorial risk profile and large portions of unexplained heritability suggest the involvement of yet unidentified genetic risk factors. Here we describe the “whole person” genetic risk landscape of polygenic risk scores for 2218 traits in 2044 elderly individuals and test if novel eigen-PRSs derived from clustered subnetworks of single-trait PRSs can improve the prediction of LOAD diagnosis, rates of cognitive decline, and canonical LOAD neuropathology. Network analyses revealed distinct clusters of PRSs with clinical and biological interpretability. Novel eigen-PRSs (ePRS) from these clusters significantly improved LOAD-related phenotypes prediction over current state-of-the-art LOAD PRS models. Notably, an ePRS representing clusters of traits related to cholesterol levels …
Authors
Amin Kharaghani,Earvin S Tio,Milos Milic,David A Bennett,Philip L De Jager,Julie A Schneider,Lei Sun,Daniel Felsky
Journal
Human Molecular Genetics
Published Date
2024/4/27
Association of 10 VEGF Family Genes with Alzheimer's Disease Pathology at Single Cell Resolution
Background The role of the vascular endothelial growth factors (VEGFs) in the pathogenesis of Alzheimer's disease (AD) has been recently described, including notable changes along the VEGFB/FLT1 signaling pathway. However, cell-type specific alterations are yet to be characterized in depth. In this study, we utilized a large single-nucleus RNA sequencing dataset (N = 424) to investigate the effect of 10 VEGF gene expression (VEGFA, VEGFB, VEGFC, VEGFD, PGF, FLT1, FLT4, KDR, NRP1, and NRP2) on cognitive performance and AD pathology, as well as on the associated VEGF signaling pathways in 8 cell types from postmortem human brains. Methods The single-nucleus transcriptomes, derived from Dorsolateral Prefrontal Cortex (DLFPC) tissues of 424 unique donors from the Religious Orders Study and Memory and Aging Project (ROS/MAP; AD Knowledge Portal syn2580853), were collected by the Rush Alzheimer's Disease Center and processed at Columbia University Medical Center. Mean age of death of the cohort was 89 years, among which 68% were females, and 52% were clinical AD cases. Negative binomial mixed models implemented in Nebula R package were used for differential expression analysis between autopsy confirmed AD dementia and normal cognition groups, and for association analysis with amyloid burden, tangle burden, and both cross-sectional and longitudinal global cognitive function. Intercellular VEGF-associated communication pattern among cell types was also profiled using CellChat. Results Higher microglia expressed FLT1, endothelial FLT4, astrocyte VEGFD, and oligodendrocyte precursor cell …
Authors
Yiyang Wu,Julia B Libby,Logan Dumitrescu,Philip L De Jager,Vilas Menon,Julie A Schneider,David A Bennett,Timothy J Hohman
Journal
bioRxiv
Published Date
2024
ZCCHC17 modulates neuronal RNA splicing and supports cognitive resilience in Alzheimer's disease
ZCCHC17 is a putative master regulator of synaptic gene dysfunction in Alzheimer's disease (AD), and ZCCHC17 protein declines early in AD brain tissue, before significant gliosis or neuronal loss. Here, we investigate the function of ZCCHC17 and its role in AD pathogenesis using data from human autopsy tissue (consisting of males and females) and female human cell lines. Co-immunoprecipitation (co-IP) of ZCCHC17 followed by mass spectrometry analysis in human iPSC-derived neurons reveals that ZCCHC17's binding partners are enriched for RNA-splicing proteins. ZCCHC17 knockdown results in widespread RNA-splicing changes that significantly overlap with splicing changes found in AD brain tissue, with synaptic genes commonly affected. ZCCHC17 expression correlates with cognitive resilience in AD patients, and we uncover an APOE4-dependent negative correlation of ZCCHC17 expression with …
Authors
Anne Marie W Bartosch,Elliot HH Youth,Shania Hansen,Yiyang Wu,Heather M Buchanan,Maria E Kaufman,Harrison Xiao,So Yeon Koo,Archana Ashok,Sharanya Sivakumar,Rajesh K Soni,Logan C Dumitrescu,Tiffany G Lam,Ali S Ropri,Annie J Lee,Hans-Ulrich Klein,Badri N Vardarajan,David A Bennett,Tracy L Young-Pearse,Philip L De Jager,Timothy J Hohman,Andrew A Sproul,Andrew F Teich
Journal
Journal of Neuroscience
Published Date
2024/1/17
CHRNA5 links chandelier cells to severity of amyloid pathology in aging and Alzheimer’s disease
Changes in high-affinity nicotinic acetylcholine receptors are intricately connected to neuropathology in Alzheimer’s Disease (AD). Protective and cognitive-enhancing roles for the nicotinic α5 subunit have been identified, but this gene has not been closely examined in the context of human aging and dementia. Therefore, we investigate the nicotinic α5 gene CHRNA5 and the impact of relevant single nucleotide polymorphisms (SNPs) in prefrontal cortex from 922 individuals with matched genotypic and post-mortem RNA sequencing in the Religious Orders Study and Memory and Aging Project (ROS/MAP). We find that a genotype robustly linked to increased expression of CHRNA5 (rs1979905A2) predicts significantly reduced cortical β-amyloid load. Intriguingly, co-expression analysis suggests CHRNA5 has a distinct cellular expression profile compared to other nicotinic receptor genes. Consistent with this …
Authors
Jonas Rybnicek,Yuxiao Chen,Milos Milic,Earvin S Tio,JoAnne McLaurin,Timothy J Hohman,Philip L De Jager,Julie A Schneider,Yanling Wang,David A Bennett,Shreejoy Tripathy,Daniel Felsky,Evelyn K Lambe
Journal
Translational Psychiatry
Published Date
2024/2/8
Post-COVID Conditions in People with Multiple Sclerosis: A Cross-sectional Multicenter Study (P1-6.002)
Objective We compared the characteristics, risk factors, and outcomes of post-COVID conditions (PCC) in people with multiple sclerosis (pwMS) with healthy controls and identified relevant risk factors and associated neurological outcomes in pwMS. Background PCC (or long-COVID) is a major public health concern. Diagnosis and management of PCC in pwMS are challenging because both conditions have similar symptoms, including fatigue, cognitive impairment, weakness, and paresthesia. Design/Methods In this cross-sectional, multi-center study, participants completed a one-time web-based survey (Aug-Dec 2022) ascertaining demographics, infections, vaccination status, neurological disease state, post-COVID symptoms (PCS), and MS outcomes. We separately evaluated new and worsening PCS that started 1 month after the initial onset of acute COVID-19 by comparing them to pre-COVID-19 baseline …
Authors
Ji Yeon Son,Chen Hu,Lindsay McAlpine,Amit Bar-Or,Megan Dahl,Sugeidy Ferreira Brito,Katelyn Kavak,Kaho Onomichi,Christopher Perrone,Claire Riley,Emily Song,Elizabeth Walker,Bianca Weinstock-Guttman,Philip De Jager,Erin Longbrake,Zongqi Xia
Published Date
2024/4/14
Professor FAQs
What is Philip L. De Jager's h-index at Columbia University in the City of New York?
The h-index of Philip L. De Jager has been 101 since 2020 and 133 in total.
What are Philip L. De Jager's top articles?
The articles with the titles of
Multi-omics and pathway analyses of genome-wide associations implicate regulation and immunity in verbal declarative memory performance
Bridging the Gap: Multi-Omics Profiling of Brain Tissue in Alzheimer's Disease and Older Controls in Multi-Ethnic Populations
Associations of Brain Morphology with Cortical Proteins of Cognitive Resilience
Association of whole-person eigen-polygenic risk scores with Alzheimer’s disease
Association of 10 VEGF Family Genes with Alzheimer's Disease Pathology at Single Cell Resolution
ZCCHC17 modulates neuronal RNA splicing and supports cognitive resilience in Alzheimer's disease
CHRNA5 links chandelier cells to severity of amyloid pathology in aging and Alzheimer’s disease
Post-COVID Conditions in People with Multiple Sclerosis: A Cross-sectional Multicenter Study (P1-6.002)
...
are the top articles of Philip L. De Jager at Columbia University in the City of New York.
What are Philip L. De Jager's research interests?
The research interests of Philip L. De Jager are: genetics, immunology, multiple sclerosis, Alzheimer, systems biology
What is Philip L. De Jager's total number of citations?
Philip L. De Jager has 94,204 citations in total.