Ala F Nassar, PhD
Senior Research ScientistCards
Contact Info
Yale School of Medicine
600 west campus drive
West Haven, CT 06516
United States
About
Titles
Senior Research Scientist
Biography
Ala F. Nassar, PhD, is a faculty member at Yale University. He has over 25 years of experience in Drug Metabolism and Preclinical Drug Development with leadership roles in both big pharma, smaller biotech firms and academics (UCONN, Brandeis and Yale). He has published more than 100 articles and chapters and holds patents in the fields of drug metabolism and bioanalytical chemistry. He leads and executes ADME-Tox experiments supporting grant projects. He was the head of the drug metabolism and bioanalytical department at Vion Pharmaceuticals, where his studies of the ADME-Tox properties of Laromustine led to a fuller, more accurate and detailed understanding of the human toxicities of the drug. He was an Ass. Professor of chemistry department and the director of Mass Spectrometry Facility at Brandeis University in Waltham, MA before coming to Yale. He has served on numerous editorial boards and is the editor of the previous edition of Drug Metabolism Handbook: Concepts and Applications and Biotransformation and Metabolite Elucidation of Xenobiotics: Characterization and Identification. Co-editor of Pharmaceutical Sciences Encyclopedia: Drug Discovery, Development & Manufacturing, 2010. He was honored as a guest editor of the special issue of Metabolites entitled "MS-Based Drug Metabolism in Cancer Research. 2021"
Courses Taught and Coordinated
General chemistry 161 and 162, Central Connecticut State University, Spring 2017
Advanced Mass Spectrometry course at Brandeis University, Fall 2011
Coordinated and taught graduate-level course on drug metabolism and bioanalytical chemistry at University of Connecticut, 2003, 2005, 2007 and 2011
Liquid Chromatography-Mass Spectrometry at Cambridge Healthtech Institute’s World Pharmaceutical Congress Annual Meeting, Philadelphia, PA 2005 and 2007
Drug Metabolism at Cambridge Healthtech Institute’s World Pharmaceutical Congress Annual Meeting, Philadelphia, PA 2007 and 2008
Capillary Electrophoresis-Mass Spectrometry, at Battelle Memorial Institute, Columbus, OH 1998
Departments & Organizations
- Chen Lab
Education & Training
- Post Doc
- UCONN/Chemistry/Pharmacology
- PhD
- UCONN, Bioanalytical/Drug Metabolism
- Visiting Scientist
- Kyushu and Nagasaki Universities
Research
Overview
Our research focuses on understanding how structure modification can improve the ADME-Tox profile for new chemical entities as they advance toward clinical candidacy. Our recent efforts use Mass Cytometry & MALDI-IHC as novel tools for Cancer Research. With their capacity for tremendous detail, these techniques produce enhanced investigative power for analyses involving simultaneous cellular profiling of multiple cell populations. Our latest endeavors are focused on an advance in single cell analysis using a hybrid mass spectrometry-flow cytometry instrument to identify and characterize rare cell types in clinical samples. Another emphasis is the development of mass spectrometric and proteomic methods for application in biological and clinical contexts to identify and quantify proteins with greater depth and coverage in a single cell.
Medical Research Interests
Public Health Interests
Research at a Glance
Yale Co-Authors
Publications Timeline
Research Interests
Adam V Wisnewski, PhD, D(ABMLI)
Jian Liu
Matthew Vesely, MD, PhD
TuKiet Lam, PhD, BS
Carrie A Redlich, MD, MPH, BA
Lieping Chen, MD, PhD
Mass Spectrometry
Single-Cell Analysis
Metabolomics
Publications
2024
Is Lipid Metabolism of Value in Cancer Research and Treatment? Part I- Lipid Metabolism in Cancer
Nassar A, Nie X, Zhang T, Yeung J, Norris P, He J, Ogura H, Babar M, Muldoon A, Libreros S, Chen L. Is Lipid Metabolism of Value in Cancer Research and Treatment? Part I- Lipid Metabolism in Cancer. Metabolites 2024, 14: 312. PMID: 38921447, PMCID: PMC11205345, DOI: 10.3390/metabo14060312.Peer-Reviewed Original ResearchConceptsMass spectrometryLipid metabolismTherapeutic efficacy of treatmentLipidomic studiesEfficacy of treatmentStudy of lipidsEmergence of lipidomicsLipid categoriesSpectrometryEnergy storageTumor microenvironmentPharmaceutical candidatesTherapeutic efficacyLipidomicsCancer patientsLipid profileCancer samplesCancerLarge-scale studiesCancer researchTargeted approachAlterationsDisease developmentCell growthMetabolismIs Lipid Metabolism of Value in Cancer Research and Treatment? Part II: Role of Specialized Pro-Resolving Mediators in Inflammation, Infections, and Cancer
Babar M, Nassar A, Nie X, Zhang T, He J, Yeung J, Norris P, Ogura H, Muldoon A, Chen L, Libreros S. Is Lipid Metabolism of Value in Cancer Research and Treatment? Part II: Role of Specialized Pro-Resolving Mediators in Inflammation, Infections, and Cancer. Metabolites 2024, 14: 314. PMID: 38921449, PMCID: PMC11205484, DOI: 10.3390/metabo14060314.Peer-Reviewed Original ResearchCitationsConceptsResolution of inflammationPro-resolving mediatorsTherapeutic effectOral squamous cell carcinomaT cell responsesSquamous cell carcinomaEicosapentaenoic acid derivativeExcessive neutrophil infiltrationDendritic cell migrationEndogenous lipid mediatorsMetastasis of cancer cellsPro-inflammatory cytokinesSpecialized pro-resolving mediatorsCell carcinomaTumor microenvironmentIschemia-related injuryLung inflammationTumor progressionNeutrophil infiltrationCell debris clearanceCystic fibrosisLung cancerAcute inflammationHerpes virusTherapeutic approachesUp-regulated PLA2G10 in cancer impairs T cell infiltration to dampen immunity.
Tianxiang Zhang, Weiwei Yu, Xiaoxiao Cheng, Jacky Yeung, Viviana Ahumada, Paul C Norris, Mackenzie J Pearson, Xuan Yang, Willemijn van Deursen, Christina Halcovich, Ala Nassar, Mathew D Vesely, Yu Zhang, Jianping Zhang, Lan Ji, Dallas B Flies, Linda Liu, Solomon Langermann, William J LaRochelle, Rachel Humphrey, Dejian Zhao, Qiuyu Zhang, Jindong Zhang, Runxia Gu, Kurt A Schalper, Miguel F Sanmamed, Lieping ChenPeer-Reviewed Original Research In Press
2022
Drug Design Strategies: Role of Structural Modifications of Drug Candidates to Improve PK Parameters of New Drugs
NASSAR A. Drug Design Strategies: Role of Structural Modifications of Drug Candidates to Improve PK Parameters of New Drugs. 2022, 323-343. DOI: 10.1002/9781119851042.ch10.Peer-Reviewed Original ResearchCitationsConceptsDrug candidatesSuccessful drug designDrug metabolism scientistsDrug designDrug discoveryStructural modificationsMetabolic stabilityDiverse propertiesActive metabolitePass metabolismToxicity relationshipsSoft drugsReactive metabolitesInhibition/inductionMetabolism studiesPharmacokinetic issuesRenal clearanceSafe drugPK parametersMetabolic clearanceMetabolic inactivationNew drugsDrugsMetabolitesClearanceAccelerating Metabolite Identification Mass Spectrometry Technology Drives Metabolite Identification Studies Forward
NASSAR A. Accelerating Metabolite Identification Mass Spectrometry Technology Drives Metabolite Identification Studies Forward. 2022, 267-302. DOI: 10.1002/9781119851042.ch8.Peer-Reviewed Original ResearchConceptsDrug candidatesDrug discoveryLC-MSLiquid chromatography-mass spectrometryChromatography-mass spectrometryMetabolite identification studiesSuccessful drug candidatesFlight mass spectrometryDrug discovery effortsMass spectrometry technologyTriple quadrupoleADMET studiesStructural assignmentMass spectrometryMetabolite characterizationLead compoundsSpectrometry technologyIon trapDiscovery effortsOverall safety profileHuman-specific metabolitesSpectrometryDrug development processMetabolism issuesMetabolite profilingCase Study: Metabolism and Reactions of Alkylating Agents in Cancer Therapy
NASSAR A, WISNEWSKI A, KING I. Case Study: Metabolism and Reactions of Alkylating Agents in Cancer Therapy. 2022, 893-922. DOI: 10.1002/9781119851042.ch26.Peer-Reviewed Original ResearchConceptsNuclear magnetic resonance spectroscopyCollision-induced dissociationFourier transform ion cyclotron resonance mass spectrometerIon cyclotron resonance mass spectrometerAccurate mass measurementsMass spectrometry studiesHydrogen-deuterium exchangeMagnetic resonance spectroscopyMass spectral rearrangementsExact massSpectrometry studiesEnzyme catalysisReactive intermediatesMass spectrometerDecomposition productsResonance spectroscopyConjugation reactionsElemental compositionPossibility of rearrangementMass measurementsSpectral rearrangementsReactionDissociationRadioactive componentsLoss of nitrogenRole of Structural Modifications of Drug Candidates to Enhance Metabolic Stability
Nassar A. Role of Structural Modifications of Drug Candidates to Enhance Metabolic Stability. 2022, 303-322. DOI: 10.1002/9781119851042.ch9.Peer-Reviewed Original ResearchCitationsConceptsDrug candidatesStructural modificationsMetabolic stabilityDrug discovery processADME propertiesMetabolite characterizationDrug designDrug discoveryBalance of propertiesToxicity relationshipsExcretion studiesMetabolic instabilityDiscovery processHuman patientsStabilityPropertiesSuccess rateModificationDrugsCandidatesCharacterizationAbsorptionPatientsChemical Structural Alert and Reactive Metabolite Concept as Applied in Medicinal Chemistry to Minimize the Toxicity of Drug Candidates
NASSAR A. Chemical Structural Alert and Reactive Metabolite Concept as Applied in Medicinal Chemistry to Minimize the Toxicity of Drug Candidates. 2022, 345-372. DOI: 10.1002/9781119851042.ch11.Peer-Reviewed Original ResearchCitationsConceptsAryl hydroxamic acidsDrug candidatesMedicinal chemistryChemical groupsQuinone methideChemical structural alertsReactive metabolitesArylpropionic acidsStructural alertsLarge clinical trialsHydroxamic acidPreclinical safety studiesToxicity problemsToxicity warningExamples of drugsPotential toxicityAdverse reactionsClinical trialsMedium-chain fatty acidsSide effectsStable metaboliteAcidHuman drugsSafety studiesNitroaromaticsDrug Metabolism Handbook: Concepts and Applications in Cancer Research
John Wiley & Sons.Books
2021
Targeting the CSF1/CSF1R axis is a potential treatment strategy for malignant meningiomas
Yeung J, Yaghoobi V, Miyagishima D, Vesely MD, Zhang T, Badri T, Nassar A, Han X, Sanmamed MF, Youngblood M, Peyre M, Kalamarides M, Rimm DL, Gunel M, Chen L. Targeting the CSF1/CSF1R axis is a potential treatment strategy for malignant meningiomas. Neuro-Oncology 2021, 23: 1922-1935. PMID: 33914067, PMCID: PMC8563319, DOI: 10.1093/neuonc/noab075.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsColony-stimulating factor-1Myeloid cellsMalignant meningiomasTumor microenvironmentCSF1/CSF1RRNA-seqRNA sequencingHuman meningiomasImmune subsetsGene expressionT cellsTreatment strategiesNormalization cancer immunotherapyImportant regulatorCell typesNovel immunocompetent murine modelDeath ligand 1 (PD-L1) expressionCell death receptor-1Immunosuppressive myeloid cellsDeath receptor-1Ligand 1 expressionFactor 1Immune cell typesImmunocompetent murine modelEffective treatment strategies
Academic Achievements & Community Involvement
activity Journal of Drug Metabolism Letters
Journal ServiceEditorial Board MemberDetails2007 - Presentactivity The American Society for Mass Spectrometry
Professional OrganizationsMemberDetails2002 - Presentactivity CT Science Fair
Public ServiceJudgeDetails03/11/2020 - Presentactivity Metabolites
Journal ServiceEditorial Board MemberDetails2018 - Presentactivity Metabolites
Journal ServiceGuest EditorDetails2023 - 2024
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- Photo by Bendall SC, et al. Trends Immunol. 2012;33:323–332.
A liquid sample containing cells labeled with heavy metal isotope-conjugated probes (ICPs) (a) is introduced into the nebulizer (b), where it is aerosolized. The aerosol droplets are directed into the ICP torch (c),
where the cells are vaporized, atomized, and ionized. Low-mass ions are
removed in the radiofrequency (RF) quadrupole ion guide (d), resulting in a cloud of ions enriched for the probe isotopes. The ion cloud then enters the time-of-flight (TOF) chamber (e),
where the ions are separated on the basis of their mass:charge ratio as
they accelerate toward the detector. Thus, the time-resolved detector
measures a mass spectrum (f) that represents the identity and quantity of each isotope on a per cell basis. Data are generated in .fcs format (g) and analyzed using the cloud-based Cytobank platform (h).
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Yale School of Medicine
600 west campus drive
West Haven, CT 06516
United States