Overview

Disorders of cholesterol metabolism underlie several human diseases, including heart disease and stroke. Recently, cholesterol metabolism has been recognized to play a major role in the pathogenesis of Alzheimer's disease. My laboratory studies genes that regulate cholesterol metabolism throughout the body, and as such we are at the interface between dementia and cardiovascular research.

Publications

Persistently elevated complement alternative pathway biomarkers in COVID-19 correlate with hypoxemia and predict in-hospital mortality
Medical Microbiology and Immunology
DOI: 10.1007/S00430-021-00725-2
2022

Small molecule inducers of ABCA1 and apoE that act through indirect activation of the LXR pathway (vol 59, pg 830, 2018)
Journal of Lipid Research
DOI: 10.1016/J.JLR.2022.100214
2022

Prognostic peripheral blood biomarkers at ICU admission predict COVID-19 clinical outcomes
Frontiers in Immunology
DOI: 10.3389/FIMMU.2022.1010216
2022

Blood Biomarkers of Brain Injury in Women who Have Experienced Intimate Partner Violence: A Pilot Study
Brain Injury
2022

Altered tau in rTg4510 mice after a single interfaced CHIMERA traumatic brain injury
BioRxiv
DOI: 10.1101/2022.09.01.506145
2022

Neurologic Prognostication After Cardiac Arrest Using Brain Biomarkers A Systematic Review and Meta-analysis
JAMA Neurology
DOI: 10.1001/JAMANEUROL.2021.5598
2022

Diffusely abnormal white matter in clinically isolated syndrome is associated with parenchymal loss and elevated neurofilament levels
Multiple Sclerosis and Related Disorders
DOI: 10.1016/J.MSARD.2021.103422
2022

Serum neurofilament light chain correlates with myelin and axonal magnetic resonance imaging markers in multiple sclerosis
Multiple Sclerosis and Related Disorders
DOI: 10.1016/J.MSARD.2021.103366
2022

PDMS Organ-On-Chip Design and Fabrication: Strategies for Improving Fluidic Integration and Chip Robustness of Rapidly Prototyped Microfluidic In Vitro Models
Micromachines
DOI: 10.3390/MI13101573
2022

Solving neurodegeneration: common mechanisms and strategies for new treatments
Molecular Neurodegeneration
DOI: 10.1186/S13024-022-00524-0
2022

Diffusely abnormal white matter in clinically isolated syndrome is associated with parenchymal loss and elevated neurofilament levels
Multiple Sclerosis Journal
2021

Soluble interleukin-6 receptor in the COVID-19 cytokine storm syndrome
Cell Reports Medicine
DOI: 10.1016/J.XCRM.2021.100269
2021

Review of Design Considerations for Brain-on-a-Chip Models
Micromachines
DOI: 10.3390/MI12040441
2021

Assessing the importance of interleukin-6 in COVID-19
The Lancet Respiratory Medicine
DOI: 10.1016/S2213-2600(20)30600-7
2021

Brain Hypoxia Is Associated With Neuroglial Injury in Humans Post-Cardiac Arrest
Circulation Research
DOI: 10.1161/CIRCRESAHA.121.319157
2021

CHIMERA TRAUMATIC BRAIN INJURY IN A MOUSE MODEL OF TAUOPATHY
Journal of Neurotrauma
2021

Correlations of Serum Neurofilaments with Myelin, Axonal and Volumetric Imaging Across the Multiple Sclerosis Spectrum
Multiple Sclerosis Journal
2021

Red blood cell transfusion in animal models of acute brain injuries: a systematic review protocol
Systematic Reviews
DOI: 10.1186/S13643-021-01703-8
2021

Blood-based traumatic brain injury biomarkers - Clinical utilities and regulatory pathways in the United States, Europe and Canada
Expert Review of Molecular Diagnostics
DOI: 10.1080/14737159.2021.2005583
2021

Characterization of Cerebrospinal Fluid Ubiquitin C-Terminal Hydrolase L1 (UCH-L1) as a Biomarker of Human Acute Traumatic Spinal Cord Injury
Journal of Neurotrauma
DOI: 10.1089/NEU.2020.7352
2021

Weathering the COVID-19 storm: Lessons from hematologic cytokine syndromes
Blood Reviews
DOI: 10.1016/J.BLRE.2020.100707
2021

Development of a novel, sensitive translational immunoassay to detect plasma glial fibrillary acidic protein (GFAP) after murine traumatic brain injury
Alzheimer's Research & Therapy
DOI: 10.1186/S13195-021-00793-9
2021

Confronting the controversy: interleukin-6 and the COVID-19 cytokine storm syndrome
European Respiratory Journal
DOI: 10.1183/13993003.03006-2020
2020

Vascular Contributions to Cognitive Impairment and Dementia (VCID): A Report from the 2018 National Heart, Lung, and Blood Institute and National Institute of Neurological Disorders and Stroke Workshop
Alzheimer's & Dementia: The Journal of the Alzheimer's Association
DOI: 10.1002/ALZ.12157
2020

Alternatives to amyloid for Alzheimer's disease therapies-a symposium report
Annals of the New York Academy of Sciences
DOI: 10.1111/NYAS.14371
2020

Cerebrovascular amyloid Angiopathy in bioengineered vessels is reduced by high-density lipoprotein particles enriched in Apolipoprotein E
Molecular Neurodegeneration
DOI: 10.1186/S13024-020-00366-8
2020

An Automated Kinematic Measurement System for Sagittal Plane Murine Head Impacts
Journal of Biomechanical Engineering
DOI: 10.1115/1.4046202
2020

An in vitro bioengineered model of the human arterial neurovascular unit to study neurodegenerative diseases
Molecular Neurodegeneration
DOI: 10.1186/S13024-020-00418-Z
2020

Amelioration of COVID-19-related cytokine storm syndrome: parallels to chimeric antigen receptor-T cell cytokine release syndrome
British Journal of Haematology
DOI: 10.1111/BJH.16961
2020

Increased severity of the CHIMERA model induces acute vascular injury, sub-acute deficits in memory recall, and chronic white matter gliosis
Experimental Neurology
DOI: 10.1016/J.EXPNEUROL.2019.113116
2020

Axl receptor tyrosine kinase is a regulator of apolipoprotein E
Molecular Brain
DOI: 10.1186/S13041-020-00609-1
2020

The association of ABO blood group with indices of disease severity and multiorgan dysfunction in COVID-19
Blood Advances
DOI: 10.1182/BLOODADVANCES.2020002623
2020

Technique and preliminary findings for in vivo quantification of brain motion during injurious head impacts
Journal of Biomechanics
T. Whyte and J. Liu and V. Chung and S.A. McErlane and Z.A. Abebe and K.A. McInnes and C.L. Wellington and P.A. Cripton
DOI: 10.1016/j.jbiomech.2019.07.023
10/2019

White matter hyperintensities in vascular contributions to cognitive impairment and dementia (VCID): Knowledge gaps and opportunities
Alzheimer's & Dementia: Translational Research & Clinical Interventions
DOI: 10.1016/J.TRCI.2019.02.001
2019

Primum non nocere: a call for balance when reporting on CTE
The Lancet Neurology
DOI: 10.1016/S1474-4422(19)30020-1
2019

A Rationally Designed Humanized Antibody Selective for Amyloid Beta Oligomers in Alzheimer's Disease
Scientific Reports
DOI: 10.1038/S41598-019-46306-5
2019

MODERATE CHIMERA INJURY ELICITS DIFFERENTIAL ACUTE INFLAMMATORY RESPONSES IN HUMANIZED APOE3 AND APOE4 TARGETED-REPLACEMENT MICE
Journal of Neurotrauma
2019

Vasoprotective Functions of High-Density Lipoproteins Relevant to Alzheimer's Disease Are Partially Conserved in Apolipoprotein B-Depleted Plasma
International Journal of Molecular Sciences
DOI: 10.3390/IJMS20030462
2019

CHIMERA repetitive mild traumatic brain injury induces chronic behavioural and neuropathological phenotypes in wild-type and APP/PS1 mice
Alzheimer's Research & Therapy
DOI: 10.1186/S13195-018-0461-0
2019

ApoA-I deficiency increases cortical amyloid deposition, cerebral amyloid angiopathy, cortical and hippocampal astrogliosis, and amyloid-associated astrocyte reactivity in APP/PS1 mice
Alzheimer's Research & Therapy
DOI: 10.1186/S13195-019-0497-9
2019

Characterisation of serum total tau following paediatric traumatic brain injury: a case-control study
The Lancet Child & Adolescent Health
DOI: 10.1016/S2352-4642(19)30194-4
2019

CHIMERA REPETITIVE MILD TBI INDUCES PTSD-LIKE BEHAVIOR AND CHRONIC NEUROPATHOLOGIES IN WILD-TYPE AND APP/ PS1 MICE
Journal of Neurotrauma
2019

An End-to-end System for Automatic Characterization of Iba1 Immunopositive Microglia in Whole Slide Imaging
Neuroinformatics
DOI: 10.1007/S12021-018-9405-X
2019

Technique and preliminary findings for in vivo quantification of brain motion during injurious head impacts
Journal of Biomechanics
DOI: 10.1016/J.JBIOMECH.2019.07.023
2019

HDL from an Alzheimer's disease perspective
Current Opinion in Lipidology
DOI: 10.1097/MOL.0000000000000604
2019

Repetitive closed-head impact model of engineered rotational acceleration (CHIMERA) injury in rats increases impulsivity, decreases dopaminergic innervation in the olfactory tubercle and generates white matter inflammation, tau phosphorylation and degeneration
Experimental Neurology
DOI: 10.1016/J.EXPNEUROL.2019.02.012
2019

Vascular dysfunction-The disregarded partner of Alzheimer's disease
Alzheimer's & Dementia: The Journal of the Alzheimer's Association
DOI: 10.1016/J.JALZ.2018.07.222
2019

Cerebral Microvascular Injury: A Potentially Treatable Endophenotype of Traumatic Brain Injury-Induced Neurodegeneration
Neuron
DOI: 10.1016/J.NEURON.2019.06.002
2019

CHARACTERIZATION OF SERUM TOTAL TAU FOLLOWING PEDIATRIC TRAUMATIC BRAIN INJURY
Journal of Neurotrauma
2019

A NATIONAL BIOBANK AND DATABASE FOR PATIENTS WITH TRAUMATIC BRAIN INJURY (CANTBI)
Journal of Neurotrauma
2018

Small molecule inducers of ABCA1 and apoE that act through indirect activation of the LXR pathway
Journal of Lipid Research
DOI: 10.1194/JLR.M081851
2018

Age at injury and genotype modify acute inflammatory and neurofilament-light responses to mild CHIMERA traumatic brain injury in wild-type and APP/PS1 mice
Experimental Neurology
DOI: 10.1016/J.EXPNEUROL.2017.12.007
2018

Ultracentrifugation and Depletion Methods of High-density Lipoprotein Isolation Yield Particles That Are Functionally Distinct in Some of Their Vasoprotective Functions
Arteriosclerosis, Thrombosis, and Vascular Biology
DOI: 10.1161/ATVB.38.SUPPL_1.385
2018

The pleiotropic vasoprotective functions of high density lipoproteins (HDL)
Journal of Biomedical Research
DOI: 10.7555/JBR.31.20160103
2018

A Rational Structured Epitope Defines a Distinct Subclass of Toxic Amyloid-beta Oligomers
ACS Chemical Neuroscience
DOI: 10.1021/ACSCHEMNEURO.7B00469
2018

The Canadian Traumatic Brain Injury Research Consortium: Epitomizing Collaborative Research in Canada
Journal of Neurotrauma
DOI: 10.1089/NEU.2018.5871
2018

Military-related risk factors for dementia
Alzheimer's & Dementia: The Journal of the Alzheimer's Association
DOI: 10.1016/J.JALZ.2018.08.011
2018

ADDRESSING MILD TRAUMATIC BRAIN INJURY-INDUCED HETEROGENEITY THROUGH EVALUATION OF INDIVIDUAL DIFFERENCES
Journal of Neurotrauma
2018

A PILOT STUDY FOR MEASURING MOTION OF THE IN VIVO BRAIN DURING HEAD IMPACTS USING CHIMERA
Journal of Neurotrauma
2018

MODERATE-SEVERE TRAUMATIC BRAIN INJURY ELICITS NEUROPATHOLOGICAL, BIOCHEMICAL, AND ELECTROPHYSIOLOGICAL CHANGES USING CHIMERA
Journal of Neurotrauma
2018

modCHIMERA: a novel murine closed-head model of moderate traumatic brain injury
Scientific Reports
DOI: 10.1038/S41598-018-25737-6
2018

AN AUTOMATED KINEMATIC MEASUREMENT SYSTEM FOR USE WITH THE CHIMERA MURINE MODEL OF TRAUMATIC BRAIN INJURY
Journal of Neurotrauma
2018

SERUM TOTAL TAU AS A DIAGNOSTIC AND PROGNOSTIC MARKER IN PEDIATRIC TRAUMATIC BRAIN INJURY
Journal of Neurotrauma
2018

INTERNATIONAL REGULATORY PATHWAYS FOR TBI BIOMARKER QUALIFICATION: PERSPECTIVES FROM THE INTBIR BIOMARKER WORKING GROUP
Journal of Neurotrauma
2018

Clearance of beta-amyloid is facilitated by apolipoprotein E and circulating high-density lipoproteins in bioengineered human vessels
eLife
Jerome Robert and Emily B Button and Brian Yuen and Megan Gilmour and Kevin Kang and Arvin Bahrabadi and Sophie Stukas and Wenchen Zhao and Iva Kulic and Cheryl L Wellington
DOI: 10.7554/eLife.29595
10/2017

Clearance of beta-amyloid is facilitated by apolipoprotein E and circulating high density lipoproteins in bioengineered human vessels
eLife
DOI: 10.7554/ELIFE.29595
2017

Defining the biomechanical and biological threshold of murine mild traumatic brain injury using CHIMERA (Closed Head Impact Model of Engineered Rotational Acceleration)
Experimental Neurology
DOI: 10.1016/J.EXPNEUROL.2017.03.003
2017

Frontal Traumatic Brain Injury Increases Impulsive Decision Making in Rats: A Potential Role for the Inflammatory Cytokine Interleukin-12
Journal of Neurotrauma
DOI: 10.1089/NEU.2016.4813
2017

High-Density Lipoproteins Suppress Amyloid Beta Induced Human Brain Microvascular Endothelial Cell Activation
Arteriosclerosis, Thrombosis, and Vascular Biology
2017

AGE HAS A GREATER INFLUENCE THAN AMYLOID BURDEN ON THE ACUTE RESPONSE TO MILD TRAUMATIC BRAIN INJURY IN MICE
Journal of Neurotrauma
2017

DEFINING THE BIOMECHANICAL AND BIOLOGICAL THRESHOLD OF MURINE MILD TRAUMATIC BRAIN INJURY USING CHIMERA
Journal of Neurotrauma
2017

High-density lipoproteins suppress A beta-induced PBMC adhesion to human endothelial cells in bioengineered vessels and in monoculture
Molecular Neurodegeneration
DOI: 10.1186/S13024-017-0201-0
2017

Defining an Analytic Framework to Evaluate Quantitative MRI Markers of Traumatic Axonal Injury: Preliminary Results in a Mouse Closed Head Injury Model
eNeuro
DOI: 10.1523/ENEURO.0164-17.2017
2017

Identification of a Chrysanthemic Ester as an Apolipoprotein E Inducer in Astrocytes
Plos One
DOI: 10.1371/JOURNAL.PONE.0162384
2016

Reconstituted high-density lipoproteins acutely reduce soluble brain A beta levels in symptomatic APP/PS1 mice
Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease
DOI: 10.1016/J.BBADIS.2015.10.005
2016

LINEAR HEAD KINEMATICS PREDICTS DURATION OF UNCONSCIOUSNESS AND SEVERITY OF AXONAL INJURY IN THE CHIMERA MOUSE MODEL OF CONCUSSION
Journal of Neurotrauma
2016

DTI ABNORMALITIES IN THE CLOSED HEAD INJURY MODEL OF ENGINEERED ROTATIONAL ACCELERATION (CHIMERA) MOUSE MODEL
Journal of Neurotrauma
2016

CHIMERA MILD TRAUMATIC BRAIN INJURY RESULTS IN COGNITIVE DYSFUNCTION UP TO 8-MONTHS POST INJURY IN THE APP/PS1 TRANSGENIC MOUSE
Journal of Neurotrauma
2016

Chronic Exposure to Androgenic-Anabolic Steroids Exacerbates Axonal Injury and Microgliosis in the CHIMERA Mouse Model of Repetitive Concussion
Plos One
DOI: 10.1371/JOURNAL.PONE.0146540
2016

Distinct roles for metalloproteinases during traumatic brain injury
Neurochemistry International
DOI: 10.1016/J.NEUINT.2016.02.013
2016

NEUROPATHOLOGY IN APP/PS1 MICE IS EXACERBATED AFTER CHIMERA (CLOSED-HEAD IMPACT MODEL OF ENGINEERED ROTATIONAL ACCELERATION)-INDUCED TRAUMATIC BRAIN INJURY
Journal of Cerebral Blood Flow & Metabolism
2016

Relation between plasma and brain lipids
Current Opinion in Lipidology
DOI: 10.1097/MOL.0000000000000291
2016

EXPOSURE TO ANABOLIC ANDROGENIC STEROIDS DOES NOT EXACERBATE ACUTE POST-INJURY OUTCOMES IN MICE SUBJECTED TO REPETITIVE CONCUSSION
Journal of Neurotrauma
2015

Vascular contributions to cognitive impairment and dementia including Alzheimer's disease
Alzheimer's & Dementia: The Journal of the Alzheimer's Association
DOI: 10.1016/J.JALZ.2014.10.008
2015

BIOMECHANICAL AND FUNCTIONAL CHARACTERIZATION OF CHIMERA IN AN APP/PS1 MODEL OF ALZHEIMER'S DISEASE
Journal of Neurotrauma
2015

High-density lipoproteins at the interface between central nervous system and plasma lipoprotein metabolism
Clinical Lipidology
DOI: 10.2217/CLP.14.64
2015

BIOMECHANICAL AND FUNCTIONAL CHARACTERIZATION OF CHIMERA: A NOVEL CLOSED-HEAD IMPACT MODEL OF ENGINEERED ROTATIONAL ACCELERATION
Journal of Neurotrauma
2014

Aplysinellamides A-C, Bromotyrosine-Derived Metabolites from an Australian Aplysinella sp Marine Sponge
Journal of Natural Products
DOI: 10.1021/NP500119E
2014

ApoE secretion modulating bromotyrosine derivative from the Australian marine sponge Callyspongia sp
Bioorganic & Medicinal Chemistry Letters
DOI: 10.1016/J.BMCL.2014.05.054
2014

LCAT deficiency does not impair amyloid metabolism in APP/PS1 mice
Journal of Lipid Research
DOI: 10.1194/JLR.M049940
2014

Intravenously Injected Human Apolipoprotein A-I Rapidly Enters the Central Nervous System via the Choroid Plexus
Journal of the American Heart Association
DOI: 10.1161/JAHA.114.001156
2014

Merging pathology with biomechanics using CHIMERA (Closed-Head Impact Model of Engineered Rotational Acceleration): a novel, surgery-free model of traumatic brain injury
Molecular Neurodegeneration
DOI: 10.1186/1750-1326-9-55
2014

Intravenously Injected Human Apolipoprotein A-I Rapidly Enters the Central Nervous System via the Choroid Plexus in Mice
Arteriosclerosis, Thrombosis, and Vascular Biology
2014

Development of an Engineered Base Cerebrovasculature Model to Study Alzheimer's Disease in vitro
Arteriosclerosis, Thrombosis, and Vascular Biology
2014

NEUROPATHOLOGICAL AND BIOCHEMICAL ASSESSMENT OF CHIMERA: A NOVEL CLOSED-HEAD IMPACT MODEL OF ENGINEERED ROTATIONAL ACCELERATION
Journal of Neurotrauma
2014

HDL and cholesterol handling in the brain
Cardiovascular Research
DOI: 10.1093/CVR/CVU148
2014

High-Density Lipoproteins and Cerebrovascular Integrity in Alzheimer's Disease
Cell Metabolism
DOI: 10.1016/J.CMET.2014.01.003
2014

Towards clinical management of traumatic brain injury: a review of models and mechanisms from a biomechanical perspective
Disease Models & Mechanisms
DOI: 10.1242/DMM.011320
2013

ABCA1 influences neuroinflammation and neuronal death
Neurobiology of Disease
DOI: 10.1016/J.NBD.2013.01.018
2013

Hormonal modulators of glial ABCA1 and apoE levels
Journal of Lipid Research
DOI: 10.1194/JLR.M042473
2013

LCAT deficiency in mice is associated with a diminished adrenal glucocorticoid function
Journal of Lipid Research
DOI: 10.1194/JLR.M030080
2013

The Liver X Receptor Agonist GW3965 Improves Recovery from Mild Repetitive Traumatic Brain Injury in Mice Partly through Apolipoprotein E
Plos One
DOI: 10.1371/JOURNAL.PONE.0053529
2013

Loss of Both ABCA1 and ABCG1 Results in Increased Disturbances in Islet Sterol Homeostasis, Inflammation, and Impaired beta-Cell Function
Diabetes
DOI: 10.2337/DB11-1341
2012

The LXR agonist GW3965 increases apoA-I protein levels in the central nervous system independent of ABCA1
Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids
DOI: 10.1016/J.BBALIP.2011.08.014
2012

An ABCA1-independent pathway for recycling a poorly lipidated 8.1 nm apolipoprotein E particle from glia
Journal of Lipid Research
DOI: 10.1194/JLR.M014365
2011

ApoE and cholesterol in schizophrenia and bipolar disorder: comparison of grey and white matter and relation with APOE genotype
Journal of Psychiatry & Neuroscience
DOI: 10.1503/JPN.090116
2011

ABCA1, apoE and apoA-I as potential therapeutic targets for treating Alzheimer's disease
Neurodegenerative Disease Management
DOI: 10.2217/NMT.11.23
2011

Differential effects of dietary fatty acids on the cerebral distribution of plasma-derived apo B lipoproteins with amyloid-beta
British Journal of Nutrition
DOI: 10.1017/S0007114509992194
2010

Serum lipids and gender affect trajectories of cognitive function in late life
Clinical Lipidology
DOI: 10.2217/CLP.10.46
2010

Probucol Reduces Enterocytic Amyloid-beta Relative to Chylomicron Apolipoprotein B in Mice Chronically Fed Saturated Fats
Atherosclerosis Supplements
DOI: 10.1016/J.ATHEROSCLEROSISSUP.2010.04.036
2010

Cholesterol Defect Is Marked across Multiple Rodent Models of Huntington's Disease and Is Manifest in Astrocytes
The Journal of Neuroscience
DOI: 10.1523/JNEUROSCI.0917-10.2010
2010

ATP-binding Cassette Transporter A1 Mediates the Beneficial Effects of the Liver X Receptor Agonist GW3965 on Object Recognition Memory and Amyloid Burden in Amyloid Precursor Protein/Presenilin 1 Mice
Journal of Biological Chemistry
DOI: 10.1074/JBC.M110.108100
2010

Why lipids are important for Alzheimer disease?
Molecular and Cellular Biochemistry
DOI: 10.1007/S11010-008-0012-2
2009

LCAT synthesized by primary astrocytes esterifies cholesterol on glia-derived lipoproteins
Journal of Lipid Research
DOI: 10.1194/JLR.M800584-JLR200
2009

Cognition, learning behaviour and hippocampal synaptic plasticity are not disrupted in mice over-expressing the cholesterol transporter ABCG1
Lipids in Health and Disease
DOI: 10.1186/1476-511X-8-5
2009

Specific Loss of Brain ABCA1 Increases Brain Cholesterol Uptake and Influences Neuronal Structure and Function
The Journal of Neuroscience
DOI: 10.1523/JNEUROSCI.4741-08.2009
2009

Greasing the wheels of A beta clearance in Alzheimer's Disease: The role of lipids and apolipoprotein E
BioFactors
DOI: 10.1002/BIOF.37
2009

Three-dimensional colocalization analysis of plasma-derived apolipoprotein B with amyloid plaques in APP/PS1 transgenic mice
Histochemistry and Cell Biology
DOI: 10.1007/S00418-009-0567-3
2009

Overexpression of ABCA1 reduces amyloid deposition in the PDAPP mouse model of Alzheimer disease
Journal of Clinical Investigation
DOI: 10.1172/JCI33622
2008

ABCG1 influences the brain cholesterol biosynthetic pathway but does not affect amyloid precursor protein or apolipoprotein E metabolism in vivo
Journal of Lipid Research
DOI: 10.1194/JLR.M700481-JLR200
2008

Overexpression of human ABCG1 does not affect atherosclerosis in fat-fed ApoE-deficient mice
Arteriosclerosis, Thrombosis, and Vascular Biology
DOI: 10.1161/ATVBAHA.108.168542
2008

MEDI 289-Multifunctional proligands for Alzheimer's disease therapy
Abstracts of Papers of the American Chemical Society
2007

The cholesterol transporter ABCG1 modulates the subcellular distribution and proteolytic processing of beta-amyloid precursor protein
Journal of Lipid Research
DOI: 10.1194/JLR.M600542-JLR200
2007

Physiologically regulated transgenic ABCA1 does not reduce amyloid burden or amyloid-beta peptide levels in vivo
Journal of Lipid Research
DOI: 10.1194/JLR.M600543-JLR200
2007

Cholesterol metabolism, apolipoprotein E, adenosine triphosphate-binding cassette transporters, and Alzheimer's disease
Current Opinion in Lipidology
DOI: 10.1097/MOL.0B013E32813AEABF
2007

24(S)-hydroxycholesterol participates in a liver X receptor-controlled pathway in astrocytes that regulates apolipoprotein E-mediated cholesterol efflux
Journal of Biological Chemistry
DOI: 10.1074/JBC.M601019200
2006

Wild-type huntingtin protects neurons from excitotoxicity
Journal of Neurochemistry
DOI: 10.1111/J.1471-4159.2005.03605.X
2006

Mutant Huntingtin: Nuclear translocation and cytotoxicity mediated by GAPDH
Proceedings of the National Academy of Sciences
DOI: 10.1073/PNAS.0511316103
2006

Elevated plasma triglyceride levels precede amyloid deposition in Alzheimer's disease mouse models with abundant A beta in plasma
Neurobiology of Disease
DOI: 10.1016/J.NBD.2006.06.007
2006

The absence of ABCA1 decreases soluble ApoE levels but does not diminish amyloid deposition in two murine models of Alzheimer disease
Journal of Biological Chemistry
DOI: 10.1074/JBC.M508781200
2005

Cholesterol at the crossroads: Alzheimer's disease and lipid metabolism
Clinical Genetics
DOI: 10.1111/J.0009-9163.2004.00280.X
2004

Inhibition of calpain cleavage of huntingtin reduces toxicity - Accumulation of calpain/caspase fragments in the nucleus
Journal of Biological Chemistry
DOI: 10.1074/JBC.M401267200
2004

Specific caspase interactions and amplification are involved in selective neuronal vulnerability in Huntington's disease
Cell Death and Differentiation
DOI: 10.1038/SJ.CDD.4401358
2004

Deficiency of ABCA1 impairs apolipoprotein E metabolism in brain
Journal of Biological Chemistry
DOI: 10.1074/JBC.M407962200
2004

Potentiation of NMDA receptor-mediated excitotoxicity linked with intrinsic apoptotic pathway in YAC transgenic mouse model of Huntington's disease
Molecular and Cellular Neuroscience
DOI: 10.1016/J.MCN.2003.11.014
2004

The ATP-binding cassette transporter 1 mediates lipid efflux from Sertoli cells and influences male fertility
Journal of Lipid Research
DOI: 10.1194/JLR.M400007-JLR200
2004

The contribution of hepatic adenosine triphosphate-binding cassette transporter, ABCA1, to high-density lipoprotein cholesterol levels in vivo
Journal of Investigative Medicine
DOI: 10.1097/00042871-200401001-00416
2004

Alterations of plasma lipids in mice via adenoviral-mediated hepatic overexpression of human ABCA1
Journal of Lipid Research
DOI: 10.1194/JLR.M300110-JLR200
2003

Nuclear localization of a non-caspase truncation product of atrophin-1, with an expanded polyglutamine repeat, increases cellular toxicity
Journal of Biological Chemistry
DOI: 10.1074/JBC.M211224200
2003

ABCA1 is essential for efficient basolateral cholesterol efflux during the absorption of dietary cholesterol in chickens
Journal of Biological Chemistry
DOI: 10.1074/JBC.M212377200
2003

Pro-survival effects of wild-type huntingtin in vivo
The American Journal of Human Genetics
2003

Huntingtin and huntingtin-associated protein 1 influence neuronal calcium signaling mediated by inositol-(1,4,5) triphosphate receptor type 1
The American Journal of Human Genetics
2003

Defective regulation of extracellular ion homeostasis causes peripheral neuropathy associated with agenesis of the corpus callosum
Clinical Genetics
DOI: 10.1034/J.1399-0004.2003.T01-1-00061.X
2003

Huntington's disease - Preface
Clinical Neuroscience Research
DOI: 10.1016/S1566-2772(03)00053-7
2003

A spectrum of neurological phenotypes caused by mutations in the X-linked aristaless-related homeobox gene, ARX
Clinical Genetics
DOI: 10.1034/J.1399-0004.2003.00061.X
2003

Huntingtin proteolysis in Huntington disease
Clinical Neuroscience Research
DOI: 10.1016/S1566-2772(03)00055-0
2003

Huntingtin and Huntingtin-associated protein 1 influence neuronal calcium signaling mediated by inositol-(1,4,5) triphosphate receptor type 1
Neuron
DOI: 10.1016/S0896-6273(03)00366-0
2003

ABCA1 mRNA and protein distribution patterns predict multiple different roles and levels of regulation
Laboratory Investigation
DOI: 10.1038/LABINVEST.3780421
2002

HIP14, a novel ankyrin domain-containing protein, links huntingtin to intracellular trafficking and endocytosis
Human Molecular Genetics
DOI: 10.1093/HMG/11.23.2815
2002

Protein kinase a site-specific phosphorylation regulates ATP-binding cassette A1 (ABCA1)-mediated phospholipid efflux
Journal of Biological Chemistry
DOI: 10.1074/JBC.M204923200
2002

Caspase cleavage of mutant huntingtin precedes neurodegeneration in Huntington's disease
The Journal of Neuroscience
DOI: 10.1523/JNEUROSCI.22-18-07862.2002
2002

Increased sensitivity to N-methyl-D-aspartate receptor-mediated excitotoxicity in a mouse model of Huntington's disease
Neuron
DOI: 10.1016/S0896-6273(02)00615-3
2002

Nuclear localization of a truncation product of mutant atrophin-1, increases cellular toxicity
Molecular Biology of the Cell
2002

Truncation mutations in ABCA1 suppress normal upregulation of full-length ABCA1 by 9-cis-retinoic acid and 22-R-hydroxycholesterol
Journal of Lipid Research
DOI: 10.1194/JLR.M200277-JLR200
2002

PKA site-specific phosphorylation of ABCA1 regulates ApoA-1-dependent phospholipid efflux
Circulation
2002

Truncation mutations in human ABCA1 suppress normal upregulation of wild-type ABCA1 by 9-cis-retinoic acid and 22-R-hydroxycholesterol
Circulation
2001

The Gln-Ala repeat transcriptional activator CA150 interacts with huntingtin: Neuropathologic and genetic evidence for a role in Huntington's disease pathogenesis
Proceedings of the National Academy of Sciences
DOI: 10.1073/PNAS.041566798
2001

Expanded polyglutamines in Caenorhabditis elegans cause axonal abnormalities and severe dysfunction of PLM mechanosensory neurons without cell death
Proceedings of the National Academy of Sciences
DOI: 10.1073/PNAS.231476398
2001

Mutant huntingtin enhances excitotoxic cell death
Molecular and Cellular Neuroscience
DOI: 10.1006/MCNE.2000.0909
2001

Human ABCA1 BAC transgenic mice show increased high density lipoprotein cholesterol and apoAI-dependent efflux stimulated by an internal promoter containing liver X receptor response elements in intron 1
Journal of Biological Chemistry
DOI: 10.1074/JBC.M102503200
2001

Increased HDL-C and apoA1 dependent efflux modulated by LXREs in human ABCA1 BAC transgenic mice
Circulation
2001

The road less traveled: functional recovery from neurodegeneration
Clinical Genetics
DOI: 10.1034/J.1399-0004.2000.580302.1.X
2000

Huntington disease: new insights on the role of huntingtin cleavage
Journal of Neural Transmission, Supplement
DOI: 10.1007/978-3-7091-6284-2_1
2000

Inhibiting caspase cleavage of huntingtin reduces toxicity and aggregate formation in neuronal and nonneuronal cells
Journal of Biological Chemistry
DOI: 10.1074/JBC.M001475200
2000

Huntingtin interacting protein 1 induces apoptosis via a novel caspase-dependent death effector domain
Journal of Biological Chemistry
DOI: 10.1074/JBC.M008408200
2000

Recent insights into the molecular pathogenesis of Huntington disease (vol 19, pg 385, 1999)
Seminars in Neurology
2000

Caspases and neurodegeneration: on the cutting edge of new therapeutic approaches
Clinical Genetics
DOI: 10.1034/J.1399-0004.2000.570101.X
2000

Insufficient death: autoimmune lymphoproliferative syndrome
Clinical Genetics
DOI: 10.1034/J.1399-0004.1999.560202.X
1999

Cleavage of atrophin-1 at caspase site aspartic acid 109 modulates cytotoxicity
Journal of Biological Chemistry
DOI: 10.1074/JBC.274.13.8730
1999

Recent insights into the molecular pathogenesis of Huntington disease
Seminars in Neurology
DOI: 10.1055/S-2008-1040853
1999

Kennedy's disease: Caspase cleavage of the androgen receptor is a crucial event in cytotoxicity
Journal of Neurochemistry
DOI: 10.1046/J.1471-4159.1999.0720185.X
1999

Subtype-specific enhancement of NMDA receptor currents by mutant Huntingtin
Journal of Neurochemistry
DOI: 10.1046/J.1471-4159.1999.0721890.X
1999

Disturbed interaction between Huntingtin and HIP3 implicates defects in neuronal endocytosis in the pathogenesis of HD
The American Journal of Human Genetics
1999

Inhibition of caspase cleavage of huntingtin protects neurons from toxicity and aggregate formation
The American Journal of Human Genetics
1999

New insights into the genetics of lissencephaly
Clinical Genetics
1998

Caspase cleavage of gene products associated with triplet expansion disorders generates truncated fragments containing the polyglutamine tract
Journal of Biological Chemistry
DOI: 10.1074/JBC.273.15.9158
1998

The influence of Huntingtin protein size on nuclear localization and cellular toxicity
The Journal of Cell Biology
DOI: 10.1083/JCB.141.5.1097
1998

The fatal attraction of polyglutamine-containing proteins
Clinical Genetics
DOI: 10.1111/J.1399-0004.1998.TB02687.X
1998

An unexpected cause for combined deficiency of coagulation factors V and VIII
Clinical Genetics
1998

Spinal muscular atrophy: a disease of altered RNA metabolism?
Clinical Genetics
1998

Length of huntingtin and its polyglutamine tract influences localization and frequency of intracellular aggregates
Nature Genetics
DOI: 10.1038/NG0298-150
1998

Quiescence versus apoptosis: Myc abundance determines pathway of exit from the cell cycle
Oncogene
DOI: 10.1038/SJ.ONC.1202241
1998

Of molecular interactions, mice and mechanisms: new insights into Huntington's disease
Current Opinion in Neurology
DOI: 10.1097/00019052-199708000-00003
1997

Caspase cleavage of huntingtin, atrophin-1 and androgen receptor
The American Journal of Human Genetics
1997

Development of an in vitro model for Huntington's disease: Evidence that the N-terminal domain of huntingtin is toxic to cells
The American Journal of Human Genetics
1997

HIP1, a human homologue of S-cerevisiae Sla2p, interacts with membrane-associated huntingtin in the brain
Nature Genetics
DOI: 10.1038/NG0597-44
1997

Toward understanding the molecular pathology of Huntington's Disease
Brain Pathology
DOI: 10.1111/J.1750-3639.1997.TB00897.X
1997

The transition from growth to quiescence versus apoptosis in serum-starved cells is decided by c-Myc but not by cdk2
Molecular Biology of the Cell
1997

C-myc overexpression in a tetracycline-based eukaryotic expression system affects cyclin-dependent kinase activity during apoptosis
Molecular Biology of the Cell
1996

Analysis of c-fos mRNA degradation in a tetracycline-regulated system
Molecular Biology of the Cell
1996

MULTIPLE ELEMENTS IN THE C-FOS PROTEIN-CODING REGION FACILITATE MESSENGER-RNA DEADENYLATION AND DECAY BY A MECHANISM COUPLED TO TRANSLATION
Journal of Biological Chemistry
1994

THE DESTABILIZING ELEMENTS IN THE CODING REGION OF C-FOS MESSENGER-RNA ARE RECOGNIZED AS RNA
Molecular and Cellular Biology
DOI: 10.1128/MCB.13.8.5034
1993

PHOTOSYNTHESIS GENE SUPEROPERONS IN PURPLE NONSULFUR BACTERIA - THE TIP OF THE ICEBERG
Canadian Journal of Microbiology
DOI: 10.1139/M92-003
1992

OVERLAPPING MESSENGER-RNA TRANSCRIPTS OF PHOTOSYNTHESIS GENE OPERONS IN RHODOBACTER-CAPSULATUS
Journal of Bacteriology
DOI: 10.1128/JB.173.4.1432-1443.1991
1991

FUNCTIONAL-SIGNIFICANCE OF OVERLAPPING TRANSCRIPTS OF CRTEF, BCHCA, AND PUF PHOTOSYNTHESIS GENE OPERONS IN RHODOBACTER-CAPSULATUS
Journal of Bacteriology
DOI: 10.1128/JB.173.9.2954-2961.1991
1991

LOCALIZATION OF THE RHODOBACTER-CAPSULATUS BCHCA OPERON OXYGEN-REGULATED PROMOTER
CURRENT RESEARCH IN PHOTOSYNTHESIS, VOLS 1-4
1990

STRUCTURAL-ANALYSIS OF THE RHODOBACTER-CAPSULATUS BCHC BACTERIOCHLOROPHYLL BIOSYNTHESIS GENE
Molecular Biology of Membrane-bound Complexes in Phototrophic Bacteria
1990

PROMOTER MAPPING AND NUCLEOTIDE-SEQUENCE OF THE BCHC BACTERIOCHLOROPHYLL BIOSYNTHESIS GENE FROM RHODOBACTER-CAPSULATUS
Gene
DOI: 10.1016/0378-1119(89)90111-X
1989

Research

Current Projects
ABCA1 is a cholesterol transporter that is widely expressed throughout the body. Outside the central nervous system, ABCA1 functions in the biogenesis of high-density lipoprotein (HDL), where it mediates the efflux of cholesterol and phospholipids to apolipoprotein (apo) A-I. Deficiency of ABCA1 results in lack of circulating HDL and greatly reduced levels of apoA-I. ABCA1 is also expressed in cells of the central nervous system, but its roles in brain lipid metabolism are not yet fully understood. In the brain, glia synthesize the apolipoproteins involved in central nervous system lipid metabolism. We have recently demonstrated that glial ABCA1 is required for cholesterol efflux to apoA-I and plays a key role in facilitating cholesterol efflux to apoE, which is the major apolipoprotein in the brain and a well-established risk factor for Alzheimer's disease. In both astrocytes and microglia, ABCA1 deficiency reduces lipid efflux to exogenous apoE. The impaired ability to efflux lipids in ABCA1-/- glia results in lipid accumulation in both astrocytes and microglia under normal culture conditions. Additionally, apoE secretion is compromised in ABCA1-/- astrocytes and microglia. In vivo, deficiency of ABCA1 results in a 65% decrease in apoE levels in whole brain, and a 75-80% decrease in apoE levels in hippocampus and striatum. Additionally, the effect of ABCA1 on apoE is selective, as apoJ levels are unchanged in brains ABCA1-/- mice. Taken together, these results show that glial ABCA1 is a key influence in apoE metabolism in the brain, and may affect the pathogenesis of Alzheimer's disease. We are currently testing whether deficiency or overexpression of ABCA1 affects Alzheimer's disease in vivo.

Down syndrome (DS) is a very common genetic disorder caused by inheritance of an extra copy of chromosome 21, which results in mental disability, heart defects, hearing loss, obesity, diabetes, cholesterol gallstones, and Alzheimer's disease. DS affects approximately 1 in 1000 births, and is a major concern for older mothers. One of the biggest challenges researchers face is to understand how an extra copy of genes on chromosome 21 causes DS. A significant breakthrough was the completion of the DNA sequence of chromosome 21 and the identification of 225 known or predicted genes. One candidate gene that resides on chromosome 21 is the cholesterol transporter ABCG1. ABCG1 regulates cholesterol trafficking and may therefore affect several problems associated with DS including dyslipidemia, cholesterol gallstone formation, and Alzheimer's disease, all of which are connected to cholesterol metabolism. We hypothesize that inheritance of an extra copy of ABCG1 may explain some of the features observed in patients with DS. To test this hypothesis, we have generated mice that specifically express an extra copy of human ABCG1. Importantly, we have designed these mice to mimic as closely as possible how ABCG1 would be overproduced in DS patients. The overall objective of this project is to characterize the impact of selective ABCG1 overexpression on lipid metabolism of these mice, particularly with respect to Alzheimer's disease, atherosclerosis, and cholesterol gallstone formation.