Dustin R. Wakeman, PhD
Adjunct Assistant Professor, Dept. of Psychiatry, School of MedicineAbout
Titles
Adjunct Assistant Professor, Dept. of Psychiatry, School of Medicine
Biography
Dr. Wakeman’s research goals are directed at developing stem cell based therapeutics to treat neurodevelopmental and neurodegenerative disease. His career interests include disease modeling, neural transplantation, and morphological and molecular changes in neurodegenerative diseases and aging. Dr. Wakeman’s research is primarily focused on drug discovery, preclinical safety & pharmacology assessments, and clinical development using a rationale course of animal models to predict translational clinical outcome. He is utilizing pluripotent stem cells to develop new strategies to model and treat disorders of the central nervous system. The goal is to use patient derived iPSCs as an in vitro platform to model disease-specific phenotypes and develop new drugable targets, as well as in vivo to mimic human disease in the rodent and nonhuman primate brain. Dr. Wakeman has active research programs investigating Alzheimer’s disease, Huntington’s disease, Parkinson’s disease, and several rare genetic neurological disorders.
Education & Training
- PhD
- University of California at San Diego, Biomedical Sciences (2010)
- BS
- University of Illinois at Urbana-Champaign, Biology (2003)
Research
Overview
Medical Research Interests
Research at a Glance
Publications Timeline
Research Interests
Stroke
Parkinsonian Disorders
Alzheimer Disease
Huntington Disease
Publications
2022
Intrathecal amyloid‐beta oligomer administration increases tau phosphorylation in the medial temporal lobe in the African green monkey: A nonhuman primate model of Alzheimer's disease
Wakeman DR, Weed MR, Perez SE, Cline EN, Viola KL, Wilcox KC, Moddrelle DS, Nisbett EZ, Kurian AM, Bell AF, Pike R, Jacobson PB, Klein WL, Mufson EJ, Lawrence MS, Elsworth JD. Intrathecal amyloid‐beta oligomer administration increases tau phosphorylation in the medial temporal lobe in the African green monkey: A nonhuman primate model of Alzheimer's disease. Neuropathology And Applied Neurobiology 2022, 48: e12800. PMID: 35156715, PMCID: PMC10902791, DOI: 10.1111/nan.12800.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsAdult African green monkeysAfrican green monkeysMedial temporal lobeAlzheimer's diseaseMagnetic resonance imagingIntrathecal injectionHippocampal volumeTau phosphorylationTemporal lobeGreen monkeysNonhuman primatesAD-like neuropathologyAD-like pathologyHuman Alzheimer's diseaseNonhuman primate modelNew treatment strategiesTransgenic rodent modelsAmyloid-beta oligomersAβO injectionAT8 antibodyClinical outcomesAD pathologyClinical trialsPrimate modelTreatment strategies
2020
The Future of GDNF in Parkinson's Disease
Manfredsson F, Polinski N, Subramanian T, Boulis N, Wakeman D, Mandel R. The Future of GDNF in Parkinson's Disease. Frontiers In Aging Neuroscience 2020, 12: 593572. PMID: 33364933, PMCID: PMC7750181, DOI: 10.3389/fnagi.2020.593572.Peer-Reviewed Original ResearchCitationsAltmetricChemical mutagenesis of a GPCR ligand: Detoxifying “inflammo-attraction” to direct therapeutic stem cell migration
Lee J, Zhang R, Yan M, Duggineni S, Wakeman D, Niles W, Feng Y, Chen J, Hamblin M, Han E, Gonzalez R, Fang X, Zhu Y, Wang J, Xu Y, Wenger D, Seyfried T, An J, Sidman R, Huang Z, Snyder E. Chemical mutagenesis of a GPCR ligand: Detoxifying “inflammo-attraction” to direct therapeutic stem cell migration. Proceedings Of The National Academy Of Sciences Of The United States Of America 2020, 117: 31177-31188. PMID: 33219123, PMCID: PMC7733796, DOI: 10.1073/pnas.1911444117.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsNeural stem cellsCXCR4 agonistPrototypical neurodegenerative diseaseDonor-derived cellsStem cellsCerebral cortexCNS injuryInflammatory chemokinesHost inflammationUndesirable inflammationCXCL-12Mouse modelTherapeutic impactChemokine CXCL12Stem cell propertiesCell engagementNeurodegenerative diseasesStem cell migrationNSC migrationAgonistsSynthetic functionInflammationChemokinesFundamental stem cell propertiesCXCL12Mitomycin-C treatment during differentiation of induced pluripotent stem cell-derived dopamine neurons reduces proliferation without compromising survival or function in vivo
Hiller B, Marmion D, Gross R, Thompson C, Chavez C, Brundin P, Wakeman D, McMahon C, Kordower J. Mitomycin-C treatment during differentiation of induced pluripotent stem cell-derived dopamine neurons reduces proliferation without compromising survival or function in vivo. Stem Cells Translational Medicine 2020, 10: 278-290. PMID: 32997443, PMCID: PMC7848297, DOI: 10.1002/sctm.20-0014.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsDopamine neuronsInduced pluripotent stem cellsParkinson's diseaseStem cell-derived dopamine neuronsPD cell therapyMidbrain dopamine neuronsLong-term survivalTransplant of cellsStem cellsHuman induced pluripotent stem cellsPluripotent stem cellsNeuron preparationsMitomycin C treatmentAthymic ratsDrug selectionUndesirable proliferationCell therapyRobust survivalLower proliferationVivo functionNeuronsTransplantationSurvivalProliferative cellsDiseaseA Biomarker for Predicting Responsiveness to Stem Cell Therapy Based on Mechanism-of-Action: Evidence from Cerebral Injury
Hartman R, Nathan N, Ghosh N, Pernia C, Law J, Nuryyev R, Plaia A, Yusof A, Tone B, Dulcich M, Wakeman D, Dilmac N, Niles W, Sidman R, Obenaus A, Snyder E, Ashwal S. A Biomarker for Predicting Responsiveness to Stem Cell Therapy Based on Mechanism-of-Action: Evidence from Cerebral Injury. Cell Reports 2020, 31: 107622. PMID: 32402283, DOI: 10.1016/j.celrep.2020.107622.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsHuman neural stem cellsHypoxic-ischemic injuryTherapeutic mechanismCerebral hypoxic-ischemic injuryCell therapyMolecular profileHierarchical region splittingStem cell therapyNeural stem cellsCerebral injurySelection biomarkerPredicting ResponsivenessNecrotic coreCognitive outcomesBiomarkersTherapyInjuryLesionsStem cellsResponsivenessPenumbraCellsCore volumeSalvageabilityRecipients
2017
Cell Replacement Strategies for Parkinson’s Disease
Chatterjee D, Wakeman D, Kordower J. Cell Replacement Strategies for Parkinson’s Disease. Molecular And Translational Medicine 2017, 73-83. DOI: 10.1007/978-3-319-57153-9_4.Peer-Reviewed Original ResearchCitationsConceptsCell replacement strategiesFetal graftsClinical trialsParkinson's diseaseAnimal modelsDouble-blind clinical assessmentOpen-label clinical trialCareful subject selectionDopamine cell replacementGraft-induced dyskinesiaPotential clinical efficacyProgressive neurodegenerative disorderCell transplantation therapyPrion-like transmissionStem cellsGraft microenvironmentMotor dysfunctionMotor symptomsNigrostriatal pathwayClinical efficacyReplacement therapyDopaminergic neuronsLewy bodiesSpecific therapyCell replacement therapyCryopreservation Maintains Functionality of Human iPSC Dopamine Neurons and Rescues Parkinsonian Phenotypes In Vivo
Wakeman D, Hiller B, Marmion D, McMahon C, Corbett G, Mangan K, Ma J, Little L, Xie Z, Perez-Rosello T, Guzman J, Surmeier D, Kordower J. Cryopreservation Maintains Functionality of Human iPSC Dopamine Neurons and Rescues Parkinsonian Phenotypes In Vivo. Stem Cell Reports 2017, 9: 149-161. PMID: 28579395, PMCID: PMC5511045, DOI: 10.1016/j.stemcr.2017.04.033.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsParkinson's diseaseDopamine neuronsMidbrain dopamine neuronsStem cell therapyGrafted neuronsHost striatumCell-based therapiesPluripotent stem cell therapyFunctional deficitsPrimate modelFiber innervationParkinsonian phenotypeTherapeutic efficacyTransplantation studiesCell therapyNeuronsSignificant reversalTranslational developmentBehavioral assessmentClinical applicationTherapyElectrophysiological signaturesRatsDiseaseMinimal manipulation
2015
Autologous iPSC‐derived dopamine neuron grafts show considerable promise in a nonhuman primate model of Parkinson's disease
Wakeman D. Autologous iPSC‐derived dopamine neuron grafts show considerable promise in a nonhuman primate model of Parkinson's disease. Movement Disorders 2015, 30: 1034-1034. PMID: 26095814, DOI: 10.1002/mds.26267.Peer-Reviewed Original Research
2014
Survival and Integration of Neurons Derived from Human Embryonic Stem Cells in MPTP-Lesioned Primates
Wakeman DR, Weiss S, Sladek JR, Elsworth JD, Bauereis B, Leranth C, Hurley PJ, Roth RH, Redmond DE. Survival and Integration of Neurons Derived from Human Embryonic Stem Cells in MPTP-Lesioned Primates. Cell Transplantation 2014, 23: 981-994. PMID: 23562290, DOI: 10.3727/096368913x664865.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsHuman embryonic stem cell linesEmbryonic stem cell linesHuman embryonic stem cellsEmbryonic stem cellsGene expression studiesStem cell linesGFP lentiviral vectorExpression studiesDifferentiated cellsDifferentiation protocolsDopamine neuronal survivalIntegration of neuronsNeuronal cellsNeuronal phenotypeTyrosine hydroxylaseStem cellsExtension of processesBiochemical analysisDopaminergic marker tyrosine hydroxylaseHESCCell linesIII-tubulinMidbrain of MPTPPhenotypeMembrane depolarizationPeripheral alpha‐synuclein and Parkinson's disease
Olanow C, Wakeman D, Kordower J. Peripheral alpha‐synuclein and Parkinson's disease. Movement Disorders 2014, 29: 963-966. PMID: 25043799, DOI: 10.1002/mds.25966.Peer-Reviewed Original ResearchCitationsMeSH Keywords
Academic Achievements & Community Involvement
honor Young Investigator Award
International AwardStem Cell Translational MedicineDetails12/05/2015United States