Taub Institute: Genomics Core
AN NIA-FUNDED ALZHEIMER'S DISEASE RESEARCH CENTER
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TaubCONNECT Research Perspective:
July 2025



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June 2025:

Early Proteasome Downregulation and Dysfunction Drive Proteostasis Failure in Alzheimer's Disease

HDAC Inhibitors Engage MITF and the Disease-Associated Microglia Signature to Enhance Amyloid β Uptake

The Role of Alpha-Synuclein in Synucleinopathy: Impact on Lipid Regulation at Mitochondria-ER

Associations Between Hearing Loss and Dementia in a Large Electronic Health Record System

May 2025:

CLU Alleviates Alzheimer's Disease-Relevant Processes by Modulating Astrocyte Reactivity and Microglia-Dependent Synaptic Density

Selective Removal of Astrocytic PERK Protects Against Glymphatic Impairment and Decreases Toxic Aggregation of β-Amyloid and Tau

APOE ε4-Associated Heterogeneity of Neuroimaging Biomarkers Across the Alzheimer's Disease Continuum

April 2025:

Modulation of CREB3L2-ATF4 Heterodimerization via Proteasome Inhibition and HRI Activation in Alzheimer's Disease Pathology

APOE and Alzheimer's Disease and Related Dementias Risk Among 12,221 Hispanics/Latinos

A Human Brain Map of Mitochondrial Respiratory Capacity and Diversity

Preclinical Alzheimer's Disease Shows Alterations in Circulating Neuronal-Derived Extracellular Vesicle MicroRNAs in a Multiethnic Cohort

March 2025:

ANXA11 Biomolecular Condensates Facilitate Protein-Lipid Phase Coupling on Lysosomal Membranes

Local Genetic Covariance Analysis with Lipid Traits Identifies Novel Loci for Early-Onset Alzheimer's Disease

The Association of Multilingualism with Diverse Language Families and Cognition Among Adults with and Without Education in India

Axonal Transport of CHMP2b Is Regulated by Kinesin-Binding Protein and Disrupted by CHMP2bintron5

February 2025:

Exploring the Role of T Cells in Alzheimer's and other Neurodegenerative Diseases: Emerging Therapeutic Insights from the T Cells in the Brain Symposium

Sleep Genetics and Cognitive Changes over Time: The Moderating Effect of Age and the Role of Brain

Emerging Roles for Tubulin PTMs in Neuronal Function and Neurodegenerative Disease

January 2025:

Inflammatory Biomarkers Profiles and Cognition Among Older Adults

Early Life Exposure to Structural Sexism and Late-Life Memory Trajectories Among Black and White Women and Men in the United States

The Effects of Mosaicism on Biological and Clinical Markers of Alzheimer's Disease in Adults with Down Syndrome

Plasma Phospho-tau217 as a Predictive Biomarker for Alzheimer's Disease in a Large South American Cohort

December 2024:

Synaptic and Cognitive Impairment Associated with L444P Heterozygous Glucocerebrosidase Mutation

Elevated Expression of the Retrotransposon LINE-1 Drives Alzheimer's Disease-Associated Microglial Dysfunction

"Rest of the Folks are Tired and Weary": The Impact of Historical Lynchings on Biological and Cognitive Health for Older Adults Racialized as Black

November 2024:

ABCA7-Dependent Induction of Neuropeptide Y is Required for Synaptic Resilience in Alzheimer’s Disease Through BDNF/NGFR Signaling

Regulation of Synapse Density by Pumilio RNA-Binding Proteins

CD33 and SHP-1/PTPN6 Interaction in Alzheimer's Disease

A Neural Implementation of Cognitive Reserve: Insights from a Longitudinal fMRI Study of Set-Switching in Aging

October 2024:

Cellular Communities Reveal Trajectories of Brain Ageing and Alzheimer's Disease

Alzheimer's Disease CSF Biomarkers Correlate with Early Pathology and Alterations in Neuronal and Glial Gene Expression

A Cross-Disease Resource of Living Human Microglia Identifies Disease-Enriched Subsets and Tool Compounds Recapitulating Microglial States

August 2024:

Epigenetic and Genetic Risk of Alzheimer Disease from Autopsied Brains in two Ethnic Groups

Multi-Omic Analysis of Huntington's Disease Reveals a Compensatory Astrocyte State

Cytoplasmic Vacuolation and Ectopic Formation of Perineuronal Nets Are Characteristic Pathologies of Cytomegalic Neurons in Tuberous Sclerosis

Cognitive Polygenic Index Is Associated with Occupational Complexity Over and Above Brain Morphometry

July 2024:

Xenografted Human iPSC-Derived Neurons with the Familial Alzheimer's Disease APPV717I Mutation Reveal Dysregulated Transcriptome Signatures Linked to Synaptic Function and Implicate LINGO2 as a Disease Signaling Mediator

Extended Genome-Wide Association Study Employing the African Genome Resources Panel Identifies Novel Susceptibility Loci for Alzheimer's Disease in Individuals of African Ancestry

Adult-Onset Deactivation of Autophagy Leads to loss of Synapse Homeostasis and Cognitive Impairment, with Implications for Alzheimer Disease

June 2024:

ZCCHC17 Knockdown Phenocopies Alzheimer's Disease-Related Loss of Synaptic Proteins and Hyperexcitability

Design and Methods of the Early Age-Related Hearing Loss Investigation Randomized Controlled Trial

May 2024:

Updated Safety Results From Phase 3 Lecanemab Study in Early Alzheimer's Disease

The Broken Alzheimer's Disease Genome

Personality Traits and Cognitive Reserve—High Openness Benefits Cognition in the Presence of Age-Related Brain Changes

April 2024:

Rare Genetic Variation in Fibronectin 1 (FN1) Protects Against APOEε4 in Alzheimer's Disease

Cell Subtype-Specific Effects of Genetic Variation in the Alzheimer's Disease Brain

Osteopontin Drives Neuroinflammation and Cell Loss in MAPT-N279K Frontotemporal Dementia Patient Neurons

Childhood Engagement in Cognitively Stimulating Activities Moderates Relationships Between Brain Structure and Cognitive Function in Adulthood

March 2024:

Diet, Pace of Biological Aging, and Risk of Dementia in the Framingham Heart Study

The Matrix Receptor CD44 Is Present in Astrocytes throughout the Human Central Nervous System and Accumulates in Hypoxia and Seizures

Microglia Measured by TSPO PET are Associated with Alzheimer's Disease Pathology and Mediate key Steps in a Disease Progression Model

A Comparative Study of Structural Variant Calling in WGS from Alzheimer's Disease Families

February 2024:

Glucocorticoid Stress Hormones Stimulate Vesicle-Free Tau Secretion and Spreading in the Braint

Whole Genome-Wide Sequence Analysis of Long-Lived Families (Long-Life Family Study) Identifies MTUS2 Gene Associated with Late-Onset Alzheimer's Disease

In Vivo Tau is Associated with Change in Memory and Processing Speed, but not Reasoning, in Cognitively Unimpaired Older Adults

The Effects of Insufficient Sleep and Adequate Sleep on Cognitive Function in Healthy Adults

January 2024:

Risk of Alzheimer's Disease is Associated with Longitudinal Changes in Plasma Biomarkers in the Multi-Ethnic Washington Heights-Hamilton Heights-Inwood Columbia Aging Project (WHICAP) Cohort


ZCCHC17 Modulates Neuronal RNA Splicing and Supports Cognitive Resilience in Alzheimer's Disease


Benchmarking of Deep Neural Networks for Predicting Personal Gene Expression from DNA Sequence Highlights Shortcomings


TaubCONNECT Research Perspectives: Best Poster Presentations Taub Institute Retreat November 2023


December 2023:

Objective Physical Function in the Alzheimer's Disease Continuum: Association with Cerebrospinal Fluid Biomarkers in the ALBION Study

Racial/Ethnic Disparities in Misidentification of Dementia in Medicare Claims: Results from the Washington Heights-Inwood Columbia Aging Project

Neuropsychiatric Symptoms and Trajectories of Dependence and Cognition in a Sample of Community-Dwelling Older Adults with Dementia

Effects of Lithium on Serum Brain-Derived Neurotrophic Factor in Alzheimer's Patients with Agitation


November 2023:

2023 Taub Institute Grants for Emerging Research (TIGER) Awardees!


September 2023:

Rie1 and Sgn1 Form an RNA-Binding Complex that Enforces the Meiotic Entry Cell Fate Decision

Memory and Language Cognitive Data Harmonization Across the United States and Mexico

Education as a Moderator of Help Seeking Behavior in Subjective Cognitive Decline

August 2023:

Nerve Growth Factor Receptor (Ngfr) Induces Neurogenic Plasticity by Suppressing Reactive Astroglial Lcn2/Slc22a17 Signaling in Alzheimer's Disease

Multicellular Communities are Perturbed in the Aging Human Brain and Alzheimer's Disease

Simple Topological Task-based Functional Connectivity Features Predict Longitudinal Behavioral Change of Fluid Reasoning in the RANN Cohort

The Neuropathological Landscape of Hispanic and non-Hispanic White Decedents with Alzheimer Disease

July 2023:

Caspase-9 Inhibition Confers Stronger Neuronal and Vascular Protection Compared to VEGF Neutralization in a Mouse Model of Retinal Vein Occlusion

The Early-Onset Alzheimer's Disease Whole-Genome Sequencing Project: Study Design and Methodology

Heart Failure-Induced Cognitive Dysfunction is Mediated by Intracellular Ca2+ Leak Through Ryanodine Receptor Type 2

June 2023:

Evaluation of Plasma Biomarkers for A/T/N Classification of Alzheimer Disease Among Adults of Caribbean Hispanic Ethnicity

Dietary Flavanols Restore Hippocampal-Dependent Memory in Older Adults with Lower Diet Quality and Lower Habitual Flavanol Consumption

Survey of Neuroanatomic Sampling and Staining Procedures in Alzheimer Disease Research Center Brain Banks

May 2023:

Polygenic Risk Score Penetrance & Recurrence Risk in Familial Alzheimer Disease

Effects of Brain Maintenance and Cognitive Reserve on Age-related Decline in Three Cognitive Abilities

High School Quality is Associated with Cognition 58 Years Later

Older Adults Compensate for Switch, but not Mixing Costs, Relative to Younger Adults on an Intrinsically Cued Task Switching Experiment

April 2023:

Glucocorticoid-Driven Mitochondrial Damage Stimulates Tau Pathology

A Global View of the Genetic Basis of Alzheimer Disease

ARIA in Patients Treated with Lecanemab (BAN2401) in a Phase 2 Study in Early Alzheimer's Disease

March 2023:

CREB3L2-ATF4 Heterodimerization Defines a Transcriptional hub of Alzheimer's Disease Gene Expression Linked to Neuropathology

Healthy Lifestyle Behaviors and Biological Aging in the US National Health and Nutrition Examination Surveys 1999-2018

February 2023:

Microglia Reactivity Entails Microtubule Remodeling from Acentrosomal to Centrosomal Arrays

Genuine Selective Caspase-2 Inhibition with new Irreversible Small Peptidomimetics

Costs During the Last Five Years of Life for Patients with Clinical and Pathological Confirmed Diagnosis of Lewy Body Dementia and Alzheimer's Disease


January 2023:

Histopathology of the Cerebellar Cortex in Essential Rremor and Other Neurodegenerative Motor Disorders: Comparative Analysis of 320 Brains

The Caribbean-Hispanic Alzheimer's Disease Brain Transcriptome Reveals Ancestry-Specific Disease Mechanisms

Comparison of Amyloid Burden in Individuals with Down Syndrome Versus Autosomal Dominant Alzheimer's Disease: A Cross-Sectional Study

Neuronal Membrane Proteasomes Regulate Neuronal Circuit Activity in Vivo and are Required for Learning-Induced Behavioral Plasticity

December 2022:

A Systemic Cell Stress Signal Confers Neuronal Resilience Toward Oxidative Stress in a Hedgehog-Dependent Manner

RNA Methyltransferase NSun2 Deficiency Promotes Neurodegeneration through Epitranscriptomic Regulation of Tau Phosphorylation

Cell Type-Specific Changes Identified by Single-Cell Transcriptomics in Alzheimer's Disease

Brain Aging Among Racially and Ethnically Diverse Middle-Aged and Older Adults

Association of Subjective Cognitive Decline With Progression to Dementia in a Cognitively Unimpaired Multiracial Community Sample

November 2022:

First Place: CREB3L2-ATF4 Heterodimerization Defines a Transcriptional Hub of Alzheimer's Disease Gene Expression Linked to Neuropathology

First Place: Neuroproteasome Localization and Dysfunction Modulate Pathology in Alzheimer's Disease

October 2022:

Clearance of an Amyloid-Like Translational Repressor is Governed by 14-3-3 Proteins

Diet Moderates the Effect of Resting State Functional Connectivity on Cognitive Function

Longitudinal Patterns of Cortical Atrophy on MRI in Patients With Alzheimer Disease With and Without Lewy Body Pathology

September 2022:

Crosstalk Between Acetylation and the Tyrosination/Detyrosination Cycle of α-Tubulin in Alzheimer's Disease

Deep Learning of MRI Contrast Enhancement for Mapping Cerebral Blood Volume from Single-Modal Non-Contrast Scans of Aging and Alzheimer's Disease Brains

Socioeconomic Status, Biological Aging, and Memory in a Diverse National Sample of Older US Men and Women

August 2022:

Retromer Deficiency in Tauopathy Models Enhances the Truncation and Toxicity of Tau

Aβ42 Oligomers Trigger Synaptic Loss Through CAMKK2-AMPK-Dependent Effectors Coordinating Mitochondrial Fission and Mitophagy

July 2022:

GW5074 Increases Microglial Phagocytic Activities: Potential Therapeutic Direction for Alzheimer's Disease

Cerebral Amyloid Angiopathy Interacts with Neuritic Amyloid Plaques to Promote Tau and Cognitive Decline

Amyloid, Cerebrovascular Disease, and Neurodegeneration Biomarkers Are Associated with Cognitive Trajectories in a Racially and Ethnically Diverse, Community-Based Sample

June 2022:

Genotype-Phenotype Correlation of T Cell Subtypes Reveals Senescent and Cytotoxic Genes in Alzheimer's Disease

Single Cell/Nucleus Transcriptomics Comparison in Zebrafish and Humans Reveals Common and Distinct Molecular Responses to Alzheimer's Disease

May 2022:

FMNL2 Regulates Gliovascular Interactions and Is Associated with Vascular Risk Factors and Cerebrovascular Pathology in Alzheimer’s Disease

Molecular Insights into Cell Type-Specific Roles in Alzheimer's Disease: Human Induced Pluripotent Stem Cell-Based Disease Modeling

Effects of Eph/Ephrin Signalling and Human Alzheimer's Disease-Associated EphA1 on Drosophila Behaviour and Neurophysiology

April 2022:

Progranulin Mutations in Clinical and Neuropathological Alzheimer's Disease

Wolframin is a Novel Regulator of Tau Pathology and Neurodegeneration

Clinical Trajectories at the End of Life in Dementia Patients With Alzheimer Disease and Lewy Body Neuropathologic Changes

March 2022:

Homotypic Fibrillization of TMEM106B Across Diverse Neurodegenerative Diseases

Correlation of Plasma and Neuroimaging Biomarkers in Alzheimer's Disease

Probing the Proteome to Explore Potential Correlates of Increased Alzheimer's-Related Cerebrovascular Disease in Adults with Down Syndrome

February 2022:

Tubulin Tyrosination Regulates Synaptic Function and is Disrupted in Alzheimer's Disease

Pyramidal Tract Neurons Drive Amplification of Excitatory Inputs to Striatum Through Cholinergic Interneurons

Associations Between Neuropsychiatric Symptoms and Neuropathological Diagnoses of Alzheimer Disease and Related Dementias

Longitudinal Associations Between Racial Discrimination and Hippocampal and White Matter Hyperintensity Volumes Among Older Black Adults

The Penalty of Stress - Epichaperomes Negatively Reshaping the Brain in Neurodegenerative Disorders

January 2022:

The National Institute on Aging Late-Onset Alzheimer's Disease Family Based Study: A Resource for Genetic Discovery

Atlas of RNA Editing Events Affecting Protein Expression in Aged and Alzheimer's Disease Human Brain Tissue

The Neuronal Retromer can Regulate Both Neuronal and Microglial Phenotypes of Alzheimer's Disease

Deep Learning Improves Utility of Tau PET in the Study of Alzheimer's Disease

December 2021:

Predictors of Incident Mild Cognitive Impairment and Its Course in a Diverse Community-Based Population

Atlas of RNA Editing Events Affecting Protein Expression in Aged and Alzheimer's Disease Human Brain Tissue

Integration of GWAS and Brain Transcriptomic Analyses in a Multiethnic Sample of 35,245 Older Adults Identifies DCDC2 Gene as Predictor of Episodic Memory Maintenance

November 2021:

KYNA/Ahr Signaling Suppresses Neural Stem Cell Plasticity and Neurogenesis in Adult Zebrafish Model of Alzheimer's Disease

Characterization of Mitochondrial DNA Quantity and Quality in the Human Aged and Alzheimer's Disease Brain

Self-Awareness for Financial Decision Making Abilities is Linked to Right Temporal Cortical Thickness in Older Adults

October 2021:

An Immune Response Characterizes Early Alzheimer's Disease Pathology and Subjective Cognitive Impairment in Hydrocephalus Biopsies

MEF2C Common Genetic Variation Is Associated With Different Aspects of Cognition in Non-Hispanic White and Caribbean Hispanic Non-demented Older Adults

Association of Regional White Matter Hyperintensities With Longitudinal Alzheimer-Like Pattern of Neurodegeneration in Older Adults

Age of Onset of Huntington's Disease in Carriers of Reduced Penetrance Alleles

September 2021:

Traversing the Aging Research and Health Equity Divide: Toward Intersectional Frameworks of Research Justice and Participation

Epigenomic Features Related to Microglia are Associated with Attenuated Effect of APOE ε4 on Alzheimer's Disease Risk in Humans

Caspase-9: A Multimodal Therapeutic Target With Diverse Cellular Expression in Human Disease

August 2021:

Neuropsychological Predictors of Severe Functional Dependency in a Multiethnic Community Cohort of Individuals with Alzheimer's Disease

Midlife Vascular Factors and Prevalence of Mild Cognitive Impairment in Late-Life in Mexico

Effect of Aerobic Exercise on White Matter Tract Microstructure in Young and Middle-Aged Healthy Adults

July 2021:

Quantifying Age-Related Changes in Brain and Behavior: A Longitudinal Versus Cross-Sectional Approach

The Association Between Sex and Risk of Alzheimer's Disease in Adults with Down Syndrome

June 2021:

Marked Mild Cognitive Deficits in Humanized Mouse Model of Alzheimer's-Type Tau Pathology

Rapid ATF4 Depletion Resets Synaptic Responsiveness after cLTP

Polygenic Risk Score for Alzheimer's Disease in Caribbean Hispanics

Vascular-Derived SPARC and SerpinE1 Regulate Interneuron Tangential Migration and Accelerate Functional Maturation of Human Stem Cell-Derived Interneurons

May 2021:

PAC1 Receptor–Mediated Clearance of Tau in Postsynaptic Compartments Attenuates Tau Pathology in Mouse Brain

Socioeconomic and Psychosocial Mechanisms Underlying Racial/Ethnic Disparities in Cognition Among Older Adults

Recognition Memory and Divergent Cognitive Profiles in Prodromal Genetic Frontotemporal Dementia

April 2021:

Association Between Early Psychotic Symptoms and Alzheimer's Disease Prognosis in a Community-Based Cohort

Complexity and Graded Regulation of Neuronal Cell-Type-Specific Alternative Splicing Revealed by Single-Cell RNA Sequencing

The Microtubule Cytoskeleton at the Synapse & The Synaptic Life of Microtubules

Distinct Cortical Thickness Patterns Link Disparate Cerebral Cortex Regions to Select Mobility Domains

March 2021:

Optimizing Subjective Cognitive Decline to Detect Early Cognitive Dysfunction

The AD Tau Core Spontaneously Self-Assembles and Recruits Full-Length Tau to Filaments

Olfactory Impairment is Related to Tau Pathology and Neuroinflammation in Alzheimer's Disease

Race/ethnicity and Gender Modify the Association Between Diet and Cognition in U.S. Older Adults: National Health and Nutrition Examination Survey 2011-2014

Insights Into the Role of Diet and Dietary Flavanols in Cognitive Aging: Results of a Randomized Controlled Trial

February 2021:

Plasma P-Tau181, P-Tau217, and Other Blood-Based Alzheimer's Disease Biomarkers in a Multi-Ethnic, Community Study

Pathogenic Role of Delta 2 Tubulin in Bortezomib-Induced Peripheral Neuropathy




Genome-Wide Association Studies of Alzheimer’s Disease and Related Disorders Stratified by Sex, Onset Age, and Apolipoprotein E Genotype Reveal Novel Risk Loci in African Americans

Richard Mayeux, MD, MSc   Mark W. Logue, PhD
Richard Mayeux, MD, MSc   Mark Logue, PhD

As part of a multi-institutional study led by researchers from Boston University, we recently explored how genetic risk for Alzheimer’s disease may differ across subgroups within African American populations. Using genome-wide association data from both the VA Million Veteran Program and the Alzheimer’s Disease Genetics Consortium, we stratified analyses by sex, age at onset, and APOE-ε4 status—factors that are often biologically meaningful but underexamined in combination, particularly in non-European cohorts.

Dr. Mayeux, Perspective, July, 2025, figure
Figure 2. Forest plot showing the effect sizes (odds ratios) and 95% confidence intervals for the MVP/ADGC meta-analysis results for the genome-wide significant SNPs in both the stratum in which the association was identified and the opposite stratum. The green points show the effect of rs139130053 in APOE-ε4 negative individuals (upper green point) and APOE-ε4 positive individuals (lower green point). The pink points show the effect of rs115882880 in females (upper pink point) and males (lower pink point). The blue points show the effect of rs141838133 in individuals with onset age ≥ 75 years (upper blue point) and individuals with onset age < 75 years (lower blue point).

As recently reported in Alzheimer’s Research & Therapy, this approach uncovered three genome-wide significant loci outside of the APOE region: a variant near EPHA5 associated with earlier onset cases, a signal in GRIN3B (next to ABCA7) that was strongest in females, and a variant near TSPEAR in APOE-ε4 non-carriers. These genes are implicated in pathways related to synaptic plasticity, insulin signaling, and protein degradation—mechanisms that are increasingly recognized as relevant to Alzheimer’s disease pathophysiology.

These findings add to growing evidence that stratified genetic analysis—particularly in underrepresented populations—can reveal novel risk loci that may be missed in more generalized approaches. They underscore the importance of both diverse population representation and biologically informed subgroup analysis in dementia genetics. Together, these strategies offer a more nuanced view of Alzheimer’s disease risk and help illuminate the complexity of its genetic basis across different groups.

Richard Mayeux, MD, MSc
Gertrude H. Sergievsky Professor of Neurology, Psychiatry and Epidemiology (in the Sergievsky Center and Taub Institute)
rpm2@cumc.columbia.edu

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Phase Contrast-Derived Cerebral Blood Flow is Associated with Neurodegeneration and Cerebrovascular Injury in Older Adults

Adam M. Brickman, PhD    Jennifer J. Manly, PhD   Richard Mayeux, MD, MSc
Adam M. Brickman, PhD    Jennifer J. Manly, PhD    Richard Mayeux, MD, MSc

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Adam Brickman, PhD
Professor of Neuropsychology (in Neurology, the Taub Institute for Research on Alzheimer's Disease and the Aging Brain and the Gertrude H. Sergievsky Center)
amb2139@cumc.columbia.edu

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Accelerating Biomedical Discoveries in Brain Health Through Transformative Neuropathology of Aging and Neurodegeneration

Cláudio Gouveia Roque, PhD   Hemali Phatnani, PhD   
Cláudio Gouveia Roque, PhD    Hemali Phatnani, PhD    Ulrich Hengst, PhD
 

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Page and William Black Professor of Neurology (in Pathology and Cell Biology and Neuroscience)
sp30@cumc.columbia.edu

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Title 4

   Justin S. Golub, MD, MS
James Noble, MD, MS   Justin Golub, MD, MS

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Hemali Phatnani, PhD
Assistant Professor of Neurological Sciences (in Neurology)
hp2286@cumc.columbia.edu

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