Yadong Huang, MD, PhD

Associate Investigator, Gladstone Institutes of Cardiovascular Disease and Neurological Disease
Professor
Neurology
+1 415 734-2511
Research Summary: 
Molecular Mechanisms and Therapeutic Strategies of Neurodegenerative Diseases
Mentorship Development: 

5/2021 - Sharpening your Mentoring Skills (SyMS)

Websites

Publications: 

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

Annual review of pathology

Koutsodendris N, Nelson MR, Rao A, Huang Y

An Alzheimer's-disease-protective APOE mutation.

Nature medicine

Zalocusky KA, Nelson MR, Huang Y

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

Molecular neurodegeneration

Najm R, Jones EA, Huang Y

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

Nature medicine

Wang C, Najm R, Xu Q, Jeong DE, Walker D, Balestra ME, Yoon SY, Yuan H, Li G, Miller ZA, Miller BL, Malloy MJ, Huang Y

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

PLoS medicine

Steele NZ, Carr JS, Bonham LW, Geier EG, Damotte V, Miller ZA, Desikan RS, Boehme KL, Mukherjee S, Crane PK, Kauwe JS, Kramer JH, Miller BL, Coppola G, Hollenbach JA, Huang Y, Yokoyama JS

Approaching Alzheimer's disease from a network level.

Oncotarget

Gillespie AK, Jones EA, Huang Y

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

Stem cell reports

Silva MC, Cheng C, Mair W, Almeida S, Fong H, Biswas MHU, Zhang Z, Huang Y, Temple S, Coppola G, Geschwind DH, Karydas A, Miller BL, Kosik KS, Gao FB, Steen JA, Haggarty SJ

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

Neuron

Gillespie AK, Jones EA, Lin YH, Karlsson MP, Kay K, Yoon SY, Tong LM, Nova P, Carr JS, Frank LM, Huang Y

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

Cell stem cell

Zhang M, Lin YH, Sun YJ, Zhu S, Zheng J, Liu K, Cao N, Li K, Huang Y, Ding S

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

The Journal of neuroscience : the official journal of the Society for Neuroscience

Tong LM, Yoon SY, Andrews-Zwilling Y, Yang A, Lin V, Lei H, Huang Y

Direct Reprogramming of RESTing Astrocytes.

Cell stem cell

Wang C, Fong H, Huang Y

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

The Journal of neuroscience : the official journal of the Society for Neuroscience

Knoferle J, Yoon SY, Walker D, Leung L, Gillespie AK, Tong LM, Bien-Ly N, Huang Y

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

The Journal of neuroscience : the official journal of the Society for Neuroscience

Tong LM, Djukic B, Arnold C, Gillespie AK, Yoon SY, Wang MM, Zhang O, Knoferle J, Rubenstein JL, Alvarez-Buylla A, Huang Y

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

Stem cell reports

Fong H, Wang C, Knoferle J, Walker D, Balestra ME, Tong LM, Leung L, Ring KL, Seeley WW, Karydas A, Kshirsagar MA, Boxer AL, Kosik KS, Miller BL, Huang Y

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

Journal of neurology, neurosurgery, and psychiatry

Lehmann M, Ghosh PM, Madison C, Karydas A, Coppola G, O'Neil JP, Huang Y, Miller BL, Jagust WJ, Rabinovici GD

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

PloS one

Leung L, Andrews-Zwilling Y, Yoon SY, Jain S, Ring K, Dai J, Wang MM, Tong L, Walker D, Huang Y

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

PloS one

Jain S, Yoon SY, Zhu L, Brodbeck J, Dai J, Walker D, Huang Y

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

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

Jain S, Yoon SY, Zhu L, Brodbeck J, Dai J, Walker D, Huang Y

Hilar GABAergic interneuron activity controls spatial learning and memory retrieval.

PloS one

Andrews-Zwilling Y, Gillespie AK, Kravitz AV, Nelson AB, Devidze N, Lo I, Yoon SY, Bien-Ly N, Ring K, Zwilling D, Potter GB, Rubenstein JL, Kreitzer AC, Huang Y

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

Cell stem cell

Ring KL, Tong LM, Balestra ME, Javier R, Andrews-Zwilling Y, Li G, Walker D, Zhang WR, Kreitzer AC, Huang Y

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

Neurocase

Vossel KA, Bien-Ly N, Bernardo A, Rascovsky K, Karydas A, Rabinovici GD, Sidhu M, Huang EJ, Miller BL, Huang Y, Seeley WW

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

The Journal of neuroscience : the official journal of the Society for Neuroscience

Bien-Ly N, Gillespie AK, Walker D, Yoon SY, Huang Y

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

The Journal of biological chemistry

Chen HK, Liu Z, Meyer-Franke A, Brodbeck J, Miranda RD, McGuire JG, Pleiss MA, Ji ZS, Balestra ME, Walker DW, Xu Q, Jeong DE, Budamagunta MS, Voss JC, Freedman SB, Weisgraber KH, Huang Y, Mahley RW

Kynurenine 3-monooxygenase inhibition in blood ameliorates neurodegeneration.

Cell

Zwilling D, Huang SY, Sathyasaikumar KV, Notarangelo FM, Guidetti P, Wu HQ, Lee J, Truong J, Andrews-Zwilling Y, Hsieh EW, Louie JY, Wu T, Scearce-Levie K, Patrick C, Adame A, Giorgini F, Moussaoui S, Laue G, Rassoulpour A, Flik G, Huang Y, Muchowski JM, Masliah E, Schwarcz R, Muchowski PJ

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

The Journal of biological chemistry

Brodbeck J, McGuire J, Liu Z, Meyer-Franke A, Balestra ME, Jeong DE, Pleiss M, McComas C, Hess F, Witter D, Peterson S, Childers M, Goulet M, Liverton N, Hargreaves R, Freedman S, Weisgraber KH, Mahley RW, Huang Y

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.

Proceedings of the National Academy of Sciences of the United States of America

Bien-Ly N, Andrews-Zwilling Y, Xu Q, Bernardo A, Wang C, Huang Y

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

The Journal of biological chemistry

Chen HK, Ji ZS, Dodson SE, Miranda RD, Rosenblum CI, Reynolds IJ, Freedman SB, Weisgraber KH, Huang Y, Mahley RW

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

The Journal of neuroscience : the official journal of the Society for Neuroscience

Andrews-Zwilling Y, Bien-Ly N, Xu Q, Li G, Bernardo A, Yoon SY, Zwilling D, Yan TX, Chen L, Huang Y

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

The American journal of pathology

Buttini M, Masliah E, Yu GQ, Palop JJ, Chang S, Bernardo A, Lin C, Wyss-Coray T, Huang Y, Mucke L

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

Cell stem cell

Li G, Bien-Ly N, Andrews-Zwilling Y, Xu Q, Bernardo A, Ring K, Halabisky B, Deng C, Mahley RW, Huang Y

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

Journal of neurochemistry

Tesseur I, Zhang H, Brecht W, Corn J, Gong JS, Yanagisawa K, Michikawa M, Weisgraber K, Huang Y, Wyss-Coray T

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

Proceedings of the National Academy of Sciences of the United States of America

Burt TD, Agan BK, Marconi VC, He W, Kulkarni H, Mold JE, Cavrois M, Huang Y, Mahley RW, Dolan MJ, McCune JM, Ahuja SK

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

The Journal of neuroscience : the official journal of the Society for Neuroscience

Xu Q, Walker D, Bernardo A, Brodbeck J, Balestra ME, Huang Y

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

Proceedings of the National Academy of Sciences of the United States of America

Brodbeck J, Balestra ME, Saunders AM, Roses AD, Mahley RW, Huang Y

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

The pharmacogenomics journal

Roses AD, Saunders AM, Huang Y, Strum J, Weisgraber KH, Mahley RW

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

The Journal of neuroscience : the official journal of the Society for Neuroscience

Xu Q, Bernardo A, Walker D, Kanegawa T, Mahley RW, Huang Y

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

The Journal of clinical investigation

Mahley RW, Huang Y, Weisgraber KH

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

Proceedings of the National Academy of Sciences of the United States of America

Mahley RW, Weisgraber KH, Huang Y

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

Proceedings of the National Academy of Sciences of the United States of America

Ye S, Huang Y, Müllendorff K, Dong L, Giedt G, Meng EC, Cohen FE, Kuntz ID, Weisgraber KH, Mahley RW

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

Proceedings of the National Academy of Sciences of the United States of America

Chang S, ran Ma T, Miranda RD, Balestra ME, Mahley RW, Huang Y

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

The Journal of biological chemistry

Ji ZS, Müllendorff K, Cheng IH, Miranda RD, Huang Y, Mahley RW

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

The Journal of neuroscience : the official journal of the Society for Neuroscience

Ramaswamy G, Xu Q, Huang Y, Weisgraber KH

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

Journal of lipid research

Hodoglugil U, Tanyolaç S, Williamson DW, Huang Y, Mahley RW

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

Neurobiology of aging

Raber J, Huang Y, Ashford JW

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

The Journal of biological chemistry

Xu Q, Brecht WJ, Weisgraber KH, Mahley RW, Huang Y

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

The Journal of neuroscience : the official journal of the Society for Neuroscience

Brecht WJ, Harris FM, Chang S, Tesseur I, Yu GQ, Xu Q, Dee Fish J, Wyss-Coray T, Buttini M, Mucke L, Mahley RW, Huang Y

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

Journal of molecular neuroscience : MN

Huang Y, Weisgraber KH, Mucke L, Mahley RW

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

The Journal of biological chemistry

Harris FM, Tesseur I, Brecht WJ, Xu Q, Mullendorff K, Chang S, Wyss-Coray T, Mahley RW, Huang Y

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

Proceedings of the National Academy of Sciences of the United States of America

Harris FM, Brecht WJ, Xu Q, Tesseur I, Kekonius L, Wyss-Coray T, Fish JD, Masliah E, Hopkins PC, Scearce-Levie K, Weisgraber KH, Mucke L, Mahley RW, Huang Y

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.

The Journal of neuroscience : the official journal of the Society for Neuroscience

Buttini M, Yu GQ, Shockley K, Huang Y, Jones B, Masliah E, Mallory M, Yeo T, Longo FM, Mucke L

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

Journal of lipid research

Hopkins PC, Huang Y, McGuire JG, Pitas RE

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

The Journal of biological chemistry

Ji ZS, Miranda RD, Newhouse YM, Weisgraber KH, Huang Y, Mahley RW

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

Proceedings of the National Academy of Sciences of the United States of America

Huang Y, Liu XQ, Wyss-Coray T, Brecht WJ, Sanan DA, Mahley RW

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

Journal of molecular medicine (Berlin, Germany)

Langer C, Huang Y, Cullen P, Wiesenhütter B, Mahley RW, Assmann G, von Eckardstein A

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

Arteriosclerosis, thrombosis, and vascular biology

Huang Y, Ji ZS, Brecht WJ, Rall SC, Taylor JM, Mahley RW

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

Current opinion in lipidology

Mahley RW, Huang Y

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

The Journal of biological chemistry

Huang Y, Liu XQ, Rall SC, Taylor JM, von Eckardstein A, Assmann G, Mahley RW

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

Arteriosclerosis, thrombosis, and vascular biology

Huang Y, Zhu Y, Langer C, Raabe M, Wu S, Wiesenhütter B, Seedorf U, Maeda N, Assmann G, von Eckardstein A

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

The Journal of biological chemistry

Huang Y, Schwendner SW, Rall SC, Mahley RW

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

Biochimica et biophysica acta

von Eckardstein A, Jauhiainen M, Huang Y, Metso J, Langer C, Pussinen P, Wu S, Ehnholm C, Assmann G

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

Zeitschrift fur Gastroenterologie

von Eckardstein A, Huang Y, Wu S, Assmann G

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

The Journal of clinical investigation

Huang Y, von Eckardstein A, Wu S, Assmann G

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

Arteriosclerosis, thrombosis, and vascular biology

Huang Y, von Eckardstein A, Wu S, Langer C, Assmann G

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

Arteriosclerosis, thrombosis, and vascular biology

von Eckardstein A, Huang Y, Wu S, Sarmadi AS, Schwarz S, Steinmetz A, Assmann G

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

Arteriosclerosis, thrombosis, and vascular biology

Huang Y, von Eckardstein A, Wu S, Assmann G

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

Arteriosclerosis, thrombosis, and vascular biology

von Eckardstein A, Huang Y, Wu S, Funke H, Noseda G, Assmann G

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

Current opinion in lipidology

von Eckardstein A, Huang Y, Assmann G

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

Proceedings of the National Academy of Sciences of the United States of America

Huang Y, von Eckardstein A, Wu S, Maeda N, Assmann G

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

Arteriosclerosis and thrombosis : a journal of vascular biology

Huang Y, von Eckardstein A, Assmann G