Yadong Huang, MD, PhD

Professor

Neurology

[email protected]

Research Description

Research in Huang lab focuses on the causes and progression of Alzheimer’s disease. Specifically, they study a variant of apolipoprotein E, called apolipoprotein E4 (apoE4). Approximately 60–75 percent of Alzheimer’s patients carry the apoE4 variant, making it the most important genetic risk factor for Alzheimer’s disease. The team uses mouse models and induced pluripotent stem (iPS) cells made from skin cells of patients carrying apoE4 or other mutations related to Alzheimer’s to study their effects on the development, survival, and degeneration of neurons and glial cells. In addition, Huang’s lab is working to identify drug targets, develop therapeutic strategies, and repurpose existing drugs for Alzheimer’s disease and other neurodegenerative disorders.

Current Projects

Establishing cellular and animal models for Alzheimer's disease research
Studying the regulation of apoE expression in neuronal and glial cells in the central nervous system
Investigating cell type-specific roles of apoE4 in Alzheimer’s disease and other neurodegenerative disorders
Developing therapeutic strategies targeting apoE4’s detrimental effects
Repurposing existing drugs for Alzheimer’s disease and other neurodegenerative disorders

Lab Members

Mart Amornkul

Jason Bant, PhD

Jessie Blumenfeld

Nomman Chen

Samuel De Leon

Brian Grone, PhD

Yanxia Hao

Aneeqa Hasan

Yadong Huang, MD, PhD

Emily Jones, PhD

Min Joo Kim

Nicole Koutsodendris, PhD

Yaqiao Li

Zherui Liang

Chang Liu

Maxine Nelson, PhD

Theodora Pak

Antara Rao

Dennis Tabuena, PhD

Yung-Hua Wang

Angel Wen

Min Xie, PhD

Qin Xu, PhD

Oscar Yip

Seo Yeon Yoon

Misha Zilberter, PhD

Websites

https://gladstone.org/people/yadong-huang#contact

https://labs.gladstone.org/huang/

https://bms.ucsf.edu/people/yadong-huang-md-phd

https://dscb.ucsf.edu/directory/faculty/yadong-huang-md-phd

Academic community service and committee membership:

Admission committee of Biomedical Sciences Graduate Program
Chair of the Committee for Postdoctoral Fellows and Students at Gladstone Institute of Neurological Disease (GIND)
GIND/UCSF Faculty Search Committee
Gladstone Faculty Promotion Committee
Gladstone Award Selection Committee
Gladstone CIRM Scholarship Admission Committee
National Advisory Council on Aging (NACA), NIH/NIA
Medical Scientific Advisory Council of the Alzheimer's Association of Northern California and Northern Nevada

Publications:

Apolipoprotein E and Alzheimer's Disease: Findings, Hypotheses, and Potential Mechanisms.

Early Hippocampal Sharp-Wave Ripple Deficits Predict Later Learning and Memory Impairments in an Alzheimer's Disease Mouse Model.

An Alzheimer's-disease-protective APOE mutation.

Apolipoprotein E4, inhibitory network dysfunction, and Alzheimer's disease.

Gain of toxic apolipoprotein E4 effects in human iPSC-derived neurons is ameliorated by a small-molecule structure corrector.

Fine-mapping of the human leukocyte antigen locus as a risk factor for Alzheimer disease: A case-control study.

Approaching Alzheimer's disease from a network level.

Human iPSC-Derived Neuronal Model of Tau-A152T Frontotemporal Dementia Reveals Tau-Mediated Mechanisms of Neuronal Vulnerability.

Apolipoprotein E4 Causes Age-Dependent Disruption of Slow Gamma Oscillations during Hippocampal Sharp-Wave Ripples.

Pharmacological Reprogramming of Fibroblasts into Neural Stem Cells by Signaling-Directed Transcriptional Activation.

Enhancing GABA Signaling during Middle Adulthood Prevents Age-Dependent GABAergic Interneuron Decline and Learning and Memory Deficits in ApoE4 Mice.

Direct Reprogramming of RESTing Astrocytes.

Stem cell therapy for Alzheimer's disease and related disorders: current status and future perspectives.

Apolipoprotein E4 produced in GABAergic interneurons causes learning and memory deficits in mice.

Apolipoprotein E: structure and function in lipid metabolism, neurobiology, and Alzheimer's diseases.

Inhibitory interneuron progenitor transplantation restores normal learning and memory in ApoE4 knock-in mice without or with Aß accumulation.

Genetic correction of tauopathy phenotypes in neurons derived from human induced pluripotent stem cells.

Greater medial temporal hypometabolism and lower cortical amyloid burden in ApoE4-positive AD patients.

Cellular source-specific effects of apolipoprotein (apo) E4 on dendrite arborization and dendritic spine development.

Apolipoprotein E4 causes age- and sex-dependent impairments of hilar GABAergic interneurons and learning and memory deficits in mice.

Apolipoprotein e sets the stage: response to injury triggers neuropathology.

Small-molecule structure correctors target abnormal protein structure and function: structure corrector rescue of apolipoprotein E4-associated neuropathology.

Arf4 determines dentate gyrus-mediated pattern separation by regulating dendritic spine development.

Arf4 determines dentate gyrus-mediated pattern separation by regulating dendritic spine development. PLoS One

Hilar GABAergic interneuron activity controls spatial learning and memory retrieval.

Direct reprogramming of mouse and human fibroblasts into multipotent neural stem cells with a single factor.

ApoE and TDP-43 neuropathology in two siblings with familial FTLD-motor neuron disease.

Reducing human apolipoprotein E levels attenuates age-dependent Aβ accumulation in mutant human amyloid precursor protein transgenic mice.

Alzheimer mechanisms and therapeutic strategies.

Small molecule structure correctors abolish detrimental effects of apolipoprotein E4 in cultured neurons.

Roles of apolipoprotein E4 (ApoE4) in the pathogenesis of Alzheimer's disease: lessons from ApoE mouse models.

Kynurenine 3-monooxygenase inhibition in blood ameliorates neurodegeneration.

Structure-dependent impairment of intracellular apolipoprotein E4 trafficking and its detrimental effects are rescued by small-molecule structure correctors.

C-terminal-truncated apolipoprotein (apo) E4 inefficiently clears amyloid-beta (Abeta) and acts in concert with Abeta to elicit neuronal and behavioral deficits in mice.

Apolipoprotein E4 domain interaction mediates detrimental effects on mitochondria and is a potential therapeutic target for Alzheimer disease.

Apolipoprotein E4 causes age- and Tau-dependent impairment of GABAergic interneurons, leading to learning and memory deficits in mice.

Mechanisms linking apolipoprotein E isoforms with cardiovascular and neurological diseases.

Cellular source of apolipoprotein E4 determines neuronal susceptibility to excitotoxic injury in transgenic mice.

Abeta-independent roles of apolipoprotein E4 in the pathogenesis of Alzheimer's disease.

GABAergic interneuron dysfunction impairs hippocampal neurogenesis in adult apolipoprotein E4 knockin mice.

Bioactive TGF-beta can associate with lipoproteins and is enriched in those containing apolipoprotein E3.

Alzheimer disease: multiple causes, multiple effects of apolipoprotein E4, and multiple therapeutic approaches.

Apolipoprotein E: structure determines function, from atherosclerosis to Alzheimer's disease to AIDS.

Apolipoprotein (apo) E4 enhances HIV-1 cell entry in vitro, and the APOE epsilon4/epsilon4 genotype accelerates HIV disease progression.

Intron-3 retention/splicing controls neuronal expression of apolipoprotein E in the CNS.

Rosiglitazone increases dendritic spine density and rescues spine loss caused by apolipoprotein E4 in primary cortical neurons.

Detrimental effects of apolipoprotein E4: potential therapeutic targets in Alzheimer's disease.

Atherogenic remnant lipoproteins: role for proteoglycans in trapping, transferring, and internalizing.

Molecular and cellular mechanisms of apolipoprotein E4 neurotoxicity and potential therapeutic strategies.

Complex disease-associated pharmacogenetics: drug efficacy, drug safety, and confirmation of a pathogenetic hypothesis (Alzheimer's disease).

Profile and regulation of apolipoprotein E (ApoE) expression in the CNS in mice with targeting of green fluorescent protein gene to the ApoE locus.

Putting cholesterol in its place: apoE and reverse cholesterol transport.

Commentary on "Perspective on a pathogenesis and treatment of Alzheimer's disease." Apolipoprotein E and the mitochondrial metabolic hypothesis.

Apolipoprotein E4: a causative factor and therapeutic target in neuropathology, including Alzheimer's disease.

Apolipoprotein E and Alzheimer disease.

Apolipoprotein (apo) E4 and Alzheimer's disease: unique conformational and biophysical properties of apoE4 can modulate neuropathology.

Apolipoprotein (apo) E4 enhances amyloid beta peptide production in cultured neuronal cells: apoE structure as a potential therapeutic target.

Lipid- and receptor-binding regions of apolipoprotein E4 fragments act in concert to cause mitochondrial dysfunction and neurotoxicity.

Reactivity of apolipoprotein E4 and amyloid beta peptide: lysosomal stability and neurodegeneration.

Effect of domain interaction on apolipoprotein E levels in mouse brain.

Apolipoprotein A-V: a potential modulator of plasma triglyceride levels in Turks.

Common polymorphisms of ATP binding cassette transporter A1, including a functional promoter polymorphism, associated with plasma high density lipoprotein cholesterol levels in Turks.

Increased tau phosphorylation in apolipoprotein E4 transgenic mice is associated with activation of extracellular signal-regulated kinase: modulation by zinc.

ApoE genotype accounts for the vast majority of AD risk and AD pathology.

Apolipoprotein E4 domain interaction occurs in living neuronal cells as determined by fluorescence resonance energy transfer.

Neuron-specific apolipoprotein e4 proteolysis is associated with increased tau phosphorylation in brains of transgenic mice.

Apolipoprotein E: diversity of cellular origins, structural and biophysical properties, and effects in Alzheimer's disease.

Astroglial regulation of apolipoprotein E expression in neuronal cells. Implications for Alzheimer's disease.

Carboxyl-terminal-truncated apolipoprotein E4 causes Alzheimer's disease-like neurodegeneration and behavioral deficits in transgenic mice.

Modulation of Alzheimer-like synaptic and cholinergic deficits in transgenic mice by human apolipoprotein E depends on isoform, aging, and overexpression of amyloid beta peptides but not on plaque formation.

Evidence for differential effects of apoE3 and apoE4 on HDL metabolism.

Apolipoprotein E4 potentiates amyloid beta peptide-induced lysosomal leakage and apoptosis in neuronal cells.

Apolipoprotein E fragments present in Alzheimer's disease brains induce neurofibrillary tangle-like intracellular inclusions in neurons.

Endogenous apolipoprotein E modulates cholesterol efflux and cholesteryl ester hydrolysis mediated by high-density lipoprotein-3 and lipid-free apolipoproteins in mouse peritoneal macrophages.

Overexpression of apolipoprotein E3 in transgenic rabbits causes combined hyperlipidemia by stimulating hepatic VLDL production and impairing VLDL lipolysis.

Pathogenesis of type III hyperlipoproteinemia (dysbetalipoproteinemia). Questions, quandaries, and paradoxes.

Apolipoprotein E: from atherosclerosis to Alzheimer's disease and beyond.

Overexpression and accumulation of apolipoprotein E as a cause of hypertriglyceridemia.

Apolipoprotein E2 reduces the low density lipoprotein level in transgenic mice by impairing lipoprotein lipase-mediated lipolysis of triglyceride-rich lipoproteins.

Increased expression of apolipoprotein E in transgenic rabbits results in reduced levels of very low density lipoproteins and an accumulation of low density lipoproteins in plasma.

Lipid-free apolipoprotein (apo) A-I is converted into alpha-migrating high density lipoproteins by lipoprotein-depleted plasma of normolipidemic donors and apo A-I-deficient patients but not of Tangier disease patients.

Genetic factors precipitating type III hyperlipoproteinemia in hypolipidemic transgenic mice expressing human apolipoprotein E2.

Effects of genotype and diet on cholesterol efflux into plasma and lipoproteins of normal, apolipoprotein A-I-, and apolipoprotein E-deficient mice.

Apolipoprotein E2 transgenic rabbits. Modulation of the type III hyperlipoproteinemic phenotype by estrogen and occurrence of spontaneous atherosclerosis.

A natural apolipoprotein A-I variant, apoA-I (L141R)Pisa, interferes with the formation of alpha-high density lipoproteins (HDL) but not with the formation of pre beta 1-HDL and influences efflux of cholesterol into plasma.

Hypolipidemic and hyperlipidemic phenotypes in transgenic mice expressing human apolipoprotein E2.

High-density lipoprotein cholesterol as a predictor of coronary heart disease risk. The PROCAM experience and pathophysiological implications for reverse cholesterol transport.

Phospholipid transfer protein mediated conversion of high density lipoproteins generates pre beta 1-HDL.

Uptake, transfer, and esterification of cell-derived cholesterol in plasma of patients with familial HDL-deficiency.

Effects of the apolipoprotein E polymorphism on uptake and transfer of cell-derived cholesterol in plasma.

Generation of pre-beta 1-HDL and conversion into alpha-HDL. Evidence for disturbed HDL conversion in Tangier disease.

Lipoproteins containing apolipoprotein A-IV but not apolipoprotein A-I take up and esterify cell-derived cholesterol in plasma.

Cholesterol efflux, cholesterol esterification, and cholesteryl ester transfer by LpA-I and LpA-I/A-II in native plasma.

Reverse cholesterol transport in plasma of patients with different forms of familial HDL deficiency.

Physiological role and clinical relevance of high-density lipoprotein subclasses.

A plasma lipoprotein containing only apolipoprotein E and with gamma mobility on electrophoresis releases cholesterol from cells.

Cell-derived unesterified cholesterol cycles between different HDLs and LDL for its effective esterification in plasma.