2023
Development and Pharmacochemical Characterization Discover a Novel Brain-Permeable HDAC11-Selective Inhibitor with Therapeutic Potential by Regulating Neuroinflammation in Mice
Bai P, Liu Y, Yang L, Ding W, Mondal P, Sang N, Liu G, Lu X, Ho T, Zhou Y, Wu R, Birar V, Wilks M, Tanzi R, Lin H, Zhang C, Li W, Shen S, Wang C. Development and Pharmacochemical Characterization Discover a Novel Brain-Permeable HDAC11-Selective Inhibitor with Therapeutic Potential by Regulating Neuroinflammation in Mice. Journal Of Medicinal Chemistry 2023, 66: 16075-16090. PMID: 37972387, DOI: 10.1021/acs.jmedchem.3c01491.Peer-Reviewed Original ResearchConceptsPositron emission tomographyNeuropathic painHDAC11 inhibitorsInhibition of HDAC11Histone deacetylase 11Pharmacokinetic/pharmacodynamic evaluationNeuroimmune functionMouse modelPharmacological inhibitionBrain uptakeEmission tomographyTherapeutic potentialNeurological indicationsPainTherapeutic targetHDAC11Regulating neuroinflammationNeurological disordersDrug developmentMiceInhibitorsHDAC isoformsCarbon-11Metabolic propertiesBrain
2022
Human biodistribution and radiation dosimetry of the demyelination tracer [18F]3F4AP
Brugarolas P, Wilks M, Noel J, Kaiser J, Vesper D, Ramos-Torres K, Guehl N, Macdonald-Soccorso M, Sun Y, Rice P, Yokell D, Lim R, Normandin M, El Fakhri G. Human biodistribution and radiation dosimetry of the demyelination tracer [18F]3F4AP. European Journal Of Nuclear Medicine And Molecular Imaging 2022, 50: 344-351. PMID: 36197499, PMCID: PMC9816249, DOI: 10.1007/s00259-022-05980-w.Peer-Reviewed Original ResearchConceptsRadiation dosimetryTime-activity curvesAdverse eventsEffective doseMultiple bed positionsComprehensive metabolic panelNonhuman primatesHealthy human volunteersNo adverse eventsDynamic PET scansVoltage-gated potassiumAnimal models of neurological diseasesNonhuman primate studiesModels of neurological diseasesHuman biodistributionAverage effective doseMetabolic panelDosimetryOLINDA softwareHealthy volunteersUrinary bladderPET scansDemyelinating lesionsBed positionAnimal modelsA positron emission tomography imaging probe selectively targeting the BD1 bromodomain and extra-terminal domain
Bai P, Yan L, Bagdasarian F, Wilks M, Wey H, Wang C. A positron emission tomography imaging probe selectively targeting the BD1 bromodomain and extra-terminal domain. Chemical Communications 2022, 58: 9654-9657. PMID: 35943085, PMCID: PMC9618257, DOI: 10.1039/d2cc03785h.Peer-Reviewed Original ResearchConceptsPositron emission tomography imaging studiesPositron emission tomographyNon-human primatesModerate brain uptakeImaging studiesBrain uptakePositron emission tomography imaging probeEmission tomographyBrain permeabilityBrainBromodomains of BRD2Clinical translationExtra-terminal domainTranslational potentialInhibitor developmentNeurological diseasesBinding specificity
2021
Near-Infrared Fluorescence Imaging of Carotid Plaques in an Atherosclerotic Murine Model
Wu X, Ulumben A, Long S, Katagiri W, Wilks M, Yuan H, Cortese B, Yang C, Kashiwagi S, Choi H, Normandin M, Fakhri G, Zaman R. Near-Infrared Fluorescence Imaging of Carotid Plaques in an Atherosclerotic Murine Model. Biomolecules 2021, 11: 1753. PMID: 34944397, PMCID: PMC8698491, DOI: 10.3390/biom11121753.Peer-Reviewed Original Research
2020
Evaluation of the potassium channel tracer [18F]3F4AP in rhesus macaques
Guehl N, Ramos-Torres K, Linnman C, Moon S, Dhaynaut M, Wilks M, Han P, Ma C, Neelamegam R, Zhou Y, Popko B, Correia J, Reich D, Fakhri G, Herscovitch P, Normandin M, Brugarolas P. Evaluation of the potassium channel tracer [18F]3F4AP in rhesus macaques. Cerebrovascular And Brain Metabolism Reviews 2020, 41: 1721-1733. PMID: 33090071, PMCID: PMC8221756, DOI: 10.1177/0271678x20963404.Peer-Reviewed Original ResearchConceptsFocal brain injuryMyelin repair therapyContributions of demyelinationDrivers of disabilityImaging demyelinationBrain injuryMeasurements of molecular changesTool's sensitivity to changesLower myelin contentDemyelinating lesionsNeuronal conductionImpaired conductionDemyelinationBrain penetrationGold standardRhesus macaquesInjured areaMultiple sclerosisMolecular changesMyelin sheathNeurological diseasesHigh metabolic stabilityMRI methodsMRIInjury
2018
Development and Application of FASA, a Model for Quantifying Fatty Acid Metabolism Using Stable Isotope Labeling
Argus J, Wilks M, Zhou Q, Hsieh W, Khialeeva E, Hoi X, Bui V, Xu S, Yu A, Wang E, Herschman H, Williams K, Bensinger S. Development and Application of FASA, a Model for Quantifying Fatty Acid Metabolism Using Stable Isotope Labeling. Cell Reports 2018, 25: 2919-2934.e8. PMID: 30517876, PMCID: PMC6432944, DOI: 10.1016/j.celrep.2018.11.041.Peer-Reviewed Original ResearchConceptsFatty acid metabolismHomeostasis of fatty acidsCellular fatty acid contentCellular fatty acid metabolismAcid metabolismMovement of fatty acidsPolyunsaturated fatty acid poolStable isotope labelingFatty acidsFatty acid homeostasisElongation pathwayFatty acid poolAcid homeostasisMetabolic stepsContribution of synthesisAcid poolPro-inflammatory stimuliFatty acid contentIsotope labelingInflammatory signalingAcid contentMetabolismCellsElongationAcidHeat-induced radiolabeling and fluorescence labeling of Feraheme nanoparticles for PET/SPECT imaging and flow cytometry
Yuan H, Wilks M, Normandin M, El Fakhri G, Kaittanis C, Josephson L. Heat-induced radiolabeling and fluorescence labeling of Feraheme nanoparticles for PET/SPECT imaging and flow cytometry. Nature Protocols 2018, 13: 392-412. PMID: 29370158, PMCID: PMC5966297, DOI: 10.1038/nprot.2017.133.Peer-Reviewed Original Research
2017
Mature B cells accelerate wound healing after acute and chronic diabetic skin lesions
Sîrbulescu R, Boehm C, Soon E, Wilks M, Ilieş I, Yuan H, Maxner B, Chronos N, Kaittanis C, Normandin M, Fakhri G, Orgill D, Sluder A, Poznansky M. Mature B cells accelerate wound healing after acute and chronic diabetic skin lesions. Wound Repair And Regeneration 2017, 25: 774-791. PMID: 28922523, PMCID: PMC5760362, DOI: 10.1111/wrr.12584.Peer-Reviewed Original ResearchConceptsB cell treatmentB cellsKinetics of neutrophil infiltrationImmune cell populationsNaive B cellsWild-type miceSaline-treated controlsMature B cellsGrowth-associated protein 43Wound healingIncreased collagen depositionDiabetic murine woundsObese diabetic micePro-healing responseIncreased fibroblast proliferationWound granulation tissueT cellsIncreased relative expressionNeutrophil infiltrationLive B cellsScar sizeDiabetic miceDecreased apoptosisTopical applicationMMP2 expression
2015
Limiting Cholesterol Biosynthetic Flux Spontaneously Engages Type I IFN Signaling
York AG, Williams KJ, Argus JP, Zhou QD, Brar G, Vergnes L, Gray EE, Zhen A, Wu NC, Yamada DH, Cunningham CR, Tarling EJ, Wilks MQ, Casero D, Gray DH, Yu AK, Wang ES, Brooks DG, Sun R, Kitchen SG, Wu TT, Reue K, Stetson DB, Bensinger SJ. Limiting Cholesterol Biosynthetic Flux Spontaneously Engages Type I IFN Signaling. Cell 2015, 163: 1716-1729. PMID: 26686653, PMCID: PMC4783382, DOI: 10.1016/j.cell.2015.11.045.Peer-Reviewed Original ResearchConceptsImport of cholesterolI interferonType I IFNsSTING-dependent mannerCholesterol biosynthetic pathwayI IFNsCombination of biosynthesisBiosynthetic fluxBiosynthetic pathwayLong-chain fatty acidsIsotope tracer analysisMetabolic shiftMetabolic pathwaysType I interferonCholesterol biosynthesisLipid requirementsChain fatty acidsInnate immunityBiosynthesisFatty acidsPool sizePathwayMechanistic studiesViral challengeFree cholesterolHeat‐Induced Radiolabeling of Nanoparticles for Monocyte Tracking by PET
Normandin M, Yuan H, Wilks M, Chen H, Kinsella J, Cho H, Guehl N, Absi‐Halabi N, Hosseini S, Fakhri G, Sosnovik D, Josephson L. Heat‐Induced Radiolabeling of Nanoparticles for Monocyte Tracking by PET. Angewandte Chemie International Edition 2015, 54: 13002-13006. PMID: 26368132, PMCID: PMC4754124, DOI: 10.1002/anie.201505525.Peer-Reviewed Original ResearchConceptsPositron emission tomographyRadiolabelling of nanoparticlesStandardized uptake valueNP pharmacokineticsSlow uptake processUptake valueLymph nodesCirculating monocytesMonocyte traffickingIV injectionImmune responseBlood clearanceEmission tomographyHepatic uptakeMonocytesPharmacokineticsLymphUptake processCytometryModulation of PICALM Levels Perturbs Cellular Cholesterol Homeostasis
Mercer J, Argus J, Crabtree D, Keenan M, Wilks M, Ashley J, Bensinger S, Lavau C, Wechsler D. Modulation of PICALM Levels Perturbs Cellular Cholesterol Homeostasis. PLOS ONE 2015, 10: e0129776. PMID: 26075887, PMCID: PMC4467867, DOI: 10.1371/journal.pone.0129776.Peer-Reviewed Original ResearchConceptsSingle nucleotide polymorphismsGenome-wide association studiesClathrin-mediated endocytosisCellular cholesterol homeostasisGene expression studiesExpression of genesPICALM expressionHeterologous proteinsEncode proteinsAssociation studiesPICALMNucleotide polymorphismsChromosomal translocationsExpressed proteinsCholesterol biosynthesisModulate macroautophagyCholesterol homeostasisBiological rolePathway analysisFlow cytometry analysisLDLR expressionLDL receptorLevels of LDLR expressionAlzheimer's diseasePool sizeImaging PEG-Like Nanoprobes in Tumor, Transient Ischemia, and Inflammatory Disease Models
Wilks M, Normandin M, Yuan H, Cho H, Guo Y, Herisson F, Ayata C, Wooten D, Fakhri G, Josephson L. Imaging PEG-Like Nanoprobes in Tumor, Transient Ischemia, and Inflammatory Disease Models. Bioconjugate Chemistry 2015, 26: 1061-1069. PMID: 25971846, PMCID: PMC5378316, DOI: 10.1021/acs.bioconjchem.5b00213.Peer-Reviewed Original Research
2014
Improved Modeling of In Vivo Kinetics of Slowly Diffusing Radiotracers for Tumor Imaging
Wilks M, Knowles S, Wu A, Huang S. Improved Modeling of In Vivo Kinetics of Slowly Diffusing Radiotracers for Tumor Imaging. Journal Of Nuclear Medicine 2014, 55: 1539-1544. PMID: 24994929, PMCID: PMC4334373, DOI: 10.2967/jnumed.114.140038.Peer-Reviewed Original Research
2013
An Essential Requirement for the SCAP/SREBP Signaling Axis to Protect Cancer Cells from Lipotoxicity
Williams K, Argus J, Zhu Y, Wilks M, Marbois B, York A, Kidani Y, Pourzia A, Akhavan D, Lisiero D, Komisopoulou E, Henkin A, Soto H, Chamberlain B, Vergnes L, Jung M, Torres J, Liau L, Christofk H, Prins R, Mischel P, Reue K, Graeber T, Bensinger S. An Essential Requirement for the SCAP/SREBP Signaling Axis to Protect Cancer Cells from Lipotoxicity. Cancer Research 2013, 73: 2850-2862. PMID: 23440422, PMCID: PMC3919498, DOI: 10.1158/0008-5472.can-13-0382-t.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell CycleCell Line, TumorCell ProliferationFatty Acid SynthasesGene Expression ProfilingGene Expression Regulation, NeoplasticHumansIntracellular Signaling Peptides and ProteinsMembrane ProteinsMiceMice, Inbred NODModels, StatisticalNeoplasm TransplantationNeoplasmsSignal TransductionStearoyl-CoA DesaturaseSterolsConceptsSterol regulatory element-binding proteinsFatty acid synthesisSREBP activityCellular growthFatty acid poolKey transcriptional regulatorCancer cellsFatty acid desaturationAcid synthesisAcid poolElement-binding proteinMetabolic flux analysisTranscriptional regulatorsLipid biosynthesisNovel mechanistic explanationStearoyl-CoA desaturase-1Fatty acid synthase activityCancer metabolismCancer cell growthSignaling AxisCell growthFlux analysisSynthase activityDesaturase 1Lipid profiling