Diane McMahon-Pratt, PhD
Professor Emeritus of Public HealthCards
Additional Titles
Affiliated Faculty, Yale Institute for Global Health
Contact Info
About
Titles
Professor Emeritus of Public Health
Affiliated Faculty, Yale Institute for Global HealthBiography
The research in Professor McMahon-Pratt's laboratory is concerned with the parasitic protozoan, Leishmania, which causes a spectrum of diseases known as leishmaniasis. The laboratory is interested in understanding the immune effector mechanisms in the mammalian host that are involved in the control of infection and/or pathogenesis, with the aim to developing a vaccine against leishmaniasis. The laboratory has defined target vaccine candidate molecules and is collaborating with the University of Iowa and Cambridge University in a project directed toward the development of a multi-subunit vaccine. In addition, we have collaborated with Dr. Tarek Fahmy (Yale Bioengineering) in the development of nanoparticle therapeutic treatment delivery system for leishmaniasis. In other studies, the laboratory also collaborates Drs. Al Bothwell and Eddie Chae (Immunobiology) investigating the role of DKK-1 in the regulation of the innate and T cell responses to Leishmania infection. We have long-term collaboration with scientists in Colombia. Currently, Professor McMahon-Pratt is director of NIAID R01 and Fogarty (NIH)-sponsored Programs with Centro Internacional de Entrenamiento e Investigaciones Médicas (CIDEIM) in Colombia. These programs are focused on understanding the pathology of leishmaniasis caused by Leishmania (Viannia), which predominates in South America, with the objective of designing immunological approaches for treatment and control.
Appointments
Epidemiology of Microbial Diseases
EmeritusPrimary
Other Departments & Organizations
- Epidemiology of Microbial Diseases
- Global Health Studies
- Yale Institute for Global Health
- Yale School of Public Health
- Yale Ventures
- YSPH Global Health Concentration
Education & Training
- Post-Doctoral Fellow
- Harvard Medical School (1980)
- PhD
- Harvard University, Immunology (1978)
- BS
- University of Southern California, Chemistry (1969)
Research
Overview
The research in Professor McMahon-Pratt's laboratory is concerned with the parasitic protozoan, Leishmania, which causes a spectrum of diseases known as leishmaniasis. The laboratory is interested in understanding the immune effector mechanisms in the mammalian host that are involved in the control of infection and/or pathogenesis, with the aim to developing a vaccine and/or non-toxic treatments for infection. Towards these ends, we are collaborating with Dr. Tarek Fahmy (Yale Bioengineering) in the development of nanoparticle therapeutic treatment delivery system for leishmaniasis. In other studies, the laboratory also collaborates Drs. Al Bothwell and Eddie Chae (Immunobiology) investigating the role of DKK-1 in the regulation of the innate and T cell responses to Leishmania infection. We have long-term collaboration with scientists in Colombia. Currently, Professor McMahon-Pratt is director of NIAID R01 and Fogarty (NIH)-sponsored Programs with Centro Internacional de Entrenamiento e Investigaciones Médicas (CIDEIM) in Colombia. These programs are focused on understanding the pathology of leishmaniasis caused by Leishmania (Viannia), which predominates in South America, with the objective of designing immunological approaches for treatment and control.
Currently, Professor McMahon-Pratt is director of a National Institutes of Health (NIH)-Fogarty sponsored International Program with Centro Internacional de Entrenamiento e Investigaciones Médicas (CIDEIM) in Colombia. This program is focused on understanding the pathology and epidemiology of leishmaniasis caused by Leishmania (Viannia), which predominates in South America.
- Pathogenesis and virulence factors of Leishmania (Viannia) panamensis; targeted towards vaccine development against L. (Viannia) infection
- Molecular Aspects of Vector/Host-Leishmania Interaction, a collaborative Fogarty Training Program with CIDEIM and the Universidad de Los Andes and Universidad del Valle (Colombia)
- Intervenable Host Leishmania (Viannia) Interactions, an NIH project with CIDEIM
- Investigation of the role of DKK-1 in the regulation of the innate and T cell responses to Leishmania infection in collaboration with Drs. A. Bothwell and Chae (immunobiology)
Medical Subject Headings (MeSH)
Research at a Glance
Yale Co-Authors
Publications Timeline
Research Interests
Nancy Saravia, PhD, MSc
Alfred Bothwell, PhD
Diane Krause, MD, PhD
Nancy Ruddle, PhD
John Hwa, MD, PhD, FRACP
Michael Cappello, MD
Leishmaniasis
Parasitology
Publications
2023
Leishmania major-derived lipophosphoglycan influences the host’s early immune response by inducing platelet activation and DKK1 production via TLR1/2
Ihedioha O, Sivakoses A, Beverley S, McMahon-Pratt D, Bothwell A. Leishmania major-derived lipophosphoglycan influences the host’s early immune response by inducing platelet activation and DKK1 production via TLR1/2. Frontiers In Immunology 2023, 14: 1257046. PMID: 37885890, PMCID: PMC10598878, DOI: 10.3389/fimmu.2023.1257046.Peer-Reviewed Original ResearchAltmetricMeSH Keywords and ConceptsConceptsLeukocyte-platelet aggregatesEarly immune responseImmune responsePlatelet activationHost's early immune responseCell-mediated immune responsesTh2 cell polarizationAdaptive immune responsesPro-inflammatory responsePattern recognition receptorsKey virulence factorsRecognition receptorsInfectious diseasesPathogenic moleculesEndothelial cellsWnt antagonistsInfection siteVirulence factorsTLR1/2PlateletsDickkopf1Cell typesLipophosphoglycanActivationResponse
2019
- ConceptsVaccine-based therapiesPublic health interventionsMechanism of actionTreatment of cancerCurrent vaccinesDisease preventionVaccine developmentHealth interventionsInfectious diseasesVaccinationDrug addictionVaccinePreventionTreatmentDelivery systemHospitalizationAllergyAdjuvantTherapyIllnessCancerDiseaseCDC
2017
Local Delivery of the Toll-Like Receptor 9 Ligand CpG Downregulates Host Immune and Inflammatory Responses, Ameliorating Established Leishmania (Viannia) panamensis Chronic Infection
Ehrlich AK, Fernández OL, Rodriguez-Pinto D, Castilho TM, Caridad M, Goldsmith-Pestana K, Saravia NG, McMahon-Pratt D. Local Delivery of the Toll-Like Receptor 9 Ligand CpG Downregulates Host Immune and Inflammatory Responses, Ameliorating Established Leishmania (Viannia) panamensis Chronic Infection. Infection And Immunity 2017, 85: 10.1128/iai.00981-16. PMID: 28052994, PMCID: PMC5328479, DOI: 10.1128/iai.00981-16.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsAntigen-presenting cellsPeripheral blood mononuclear cellsCutaneous leishmaniasisB cellsIL-17IL-13Inflammatory responseMouse modelToll-like receptor 9 ligand CpGAlternate therapeutic approachCurrent treatment optionsBlood mononuclear cellsMixed inflammatory responseRegulatory cell functionProduction of IFNPredominant etiologic agentDose-response effectHost immune responseCell populationsGrowth factor βCpG treatmentRegulatory cellsChemokine responsesIL-10Host Immune
2016
Targeting the HSP60/10 chaperonin systems of Trypanosoma brucei as a strategy for treating African sleeping sickness
Abdeen S, Salim N, Mammadova N, Summers CM, Goldsmith-Pestana K, McMahon-Pratt D, Schultz PG, Horwich AL, Chapman E, Johnson SM. Targeting the HSP60/10 chaperonin systems of Trypanosoma brucei as a strategy for treating African sleeping sickness. Bioorganic & Medicinal Chemistry Letters 2016, 26: 5247-5253. PMID: 27720295, DOI: 10.1016/j.bmcl.2016.09.051.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsT. brucei infectionBrucei infectionComplex treatment regimensFirst-line drugsNew therapeutic strategiesLeishmania major promastigotesAnti-parasitic potentialTreatment regimensTherapeutic windowTherapeutic strategiesCurrent drugsMajor promastigotesEncouraging initial resultsHuman liverAntibiotic resistanceGreater cytotoxicityProtozoan parasiteKidney cellsMedicinal chemistry optimizationInfectionInhibitorsPotent inhibitorBrucei parasitesDrugsCytotoxicityImmunomodulatory nanoparticles ameliorate disease in the Leishmania (Viannia) panamensis mouse model
Siefert AL, Ehrlich A, Corral MJ, Goldsmith-Pestana K, McMahon-Pratt D, Fahmy TM. Immunomodulatory nanoparticles ameliorate disease in the Leishmania (Viannia) panamensis mouse model. Biomaterials 2016, 108: 168-176. PMID: 27636154, PMCID: PMC5049880, DOI: 10.1016/j.biomaterials.2016.09.004.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsPathogen-associated molecular patternsAccumulation of MDSCsHyper-inflammatory responseOngoing immune responseCytokine IL-10Antigen-presenting cellsCurrent treatment strategiesInflammation-mediated diseasesLong treatment regimensSite of infectionNew World leishmaniasisCellular immunomodulationIL-17Suppressor cellsDendritic cellsIL-10Immunotherapeutic approachesChronic inflammationTreatment regimensIL-13Free CpGTreatment strategiesTherapeutic effectImmune responsePreclinical studiesLeishmania‐encoded orthologs of macrophage migration inhibitory factor regulate host immunity to promote parasite persistence
Holowka T, Castilho TM, Garcia AB, Sun T, McMahon‐Pratt D, Bucala R. Leishmania‐encoded orthologs of macrophage migration inhibitory factor regulate host immunity to promote parasite persistence. The FASEB Journal 2016, 30: 2249-2265. PMID: 26956417, PMCID: PMC4871794, DOI: 10.1096/fj.201500189r.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsMeSH KeywordsAnimalsAntigens, Differentiation, B-LymphocyteApoptosisCD4-Positive T-LymphocytesCloning, MolecularGene DeletionGene Expression RegulationHistocompatibility Antigens Class IILeishmania majorLeishmaniasis, CutaneousMacrophage Migration-Inhibitory FactorsMacrophagesMiceMice, Inbred BALB CMice, Inbred C57BLMice, KnockoutMice, SCIDOrganisms, Genetically ModifiedProtein Array AnalysisProtozoan ProteinsConceptsMacrophage migration inhibitory factorMigration inhibitory factorCD4 T cellsInhibitory factorL. majorT cellsHost immunityProtective CD4 T cellsEffector CD4 T cellsCytokine macrophage migration inhibitory factorMajor-infected miceT cell primingAntigen-presenting cellsT cell formationExpression of IFNDeath-1Functional exhaustionIL-7RHost responseParasite persistenceParasite burdenParasite growthReduced expressionMiceSignificant differencesThe Wnt Antagonist Dickkopf-1 Promotes Pathological Type 2 Cell-Mediated Inflammation
Chae WJ, Ehrlich AK, Chan PY, Teixeira AM, Henegariu O, Hao L, Shin JH, Park JH, Tang WH, Kim ST, Maher SE, Goldsmith-Pestana K, Shan P, Hwa J, Lee PJ, Krause DS, Rothlin CV, McMahon-Pratt D, Bothwell AL. The Wnt Antagonist Dickkopf-1 Promotes Pathological Type 2 Cell-Mediated Inflammation. Immunity 2016, 44: 246-258. PMID: 26872695, PMCID: PMC4758884, DOI: 10.1016/j.immuni.2016.01.008.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsMeSH KeywordsAnimalsAntigens, DermatophagoidesAntigens, ProtozoanAsthmaBlood PlateletsCell DifferentiationCells, CulturedCytokinesExtracellular Signal-Regulated MAP KinasesGene Expression RegulationHumansInflammationIntercellular Signaling Peptides and ProteinsLeishmania majorLeishmaniasis, CutaneousMiceMice, Inbred BALB CMice, Inbred C57BLMice, TransgenicModels, AnimalPyroglyphidaeSignal TransductionTh2 CellsTOR Serine-Threonine KinasesWnt ProteinsConceptsCell-mediated inflammationTh2 cell cytokine productionCell cytokine productionLeukocyte-platelet aggregatesLeukocyte infiltrationDkk-1Cytokine productionT helper 2 cellsLeishmania major infectionHouse dust miteTranscription factor c-MafAllergen challengeMajor infectionDust miteImmune responseDickkopf-1Parasitic infectionsGATA-3Pathological roleFunctional inhibitionInflammationC-MafP38 MAPKInfiltrationInfectionThe Src kinases Hck, Fgr and Lyn activate Arg to facilitate IgG-mediated phagocytosis and Leishmania infection
Wetzel DM, Rhodes EL, Li S, McMahon-Pratt D, Koleske AJ. The Src kinases Hck, Fgr and Lyn activate Arg to facilitate IgG-mediated phagocytosis and Leishmania infection. Journal Of Cell Science 2016, 129: 3130-3143. PMID: 27358479, PMCID: PMC5004897, DOI: 10.1242/jcs.185595.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsMeSH KeywordsAniline CompoundsAnimalsCytokinesDisease Models, AnimalImatinib MesylateImmunoglobulin GLeishmaniaLeishmaniasisMacrophagesMiceModels, BiologicalNitrilesParasitesPhagocytosisPhosphorylationProtein-Tyrosine KinasesProto-Oncogene ProteinsProto-Oncogene Proteins c-hckPyrimidinesQuinolinesRAW 264.7 CellsSignal TransductionSrc-Family KinasesConceptsAmastigote uptakeObligate intracellular parasite LeishmaniaImmunoglobulin-mediated phagocytosisIntracellular parasite LeishmaniaNovel therapeutic strategiesPersistence of infectionLeishmania infectionIgG-mediated phagocytosisTherapeutic strategiesFc receptorsSmall molecule inhibitorsArg activationDisease severityParasite burdenPrimary macrophagesMacrophagesKinase inhibitorsLeishmaniasisHuman hostDevastating diseaseInfectionParasite LeishmaniaSrc family kinasesPhagocytosisLeishmania
2015
Cutaneous leishmaniasis is regulated by Wnt antagonist Dkk-1 from activated platelets (MPF7P.715)
Bothwell A, Chae W, Ehrlich A, Teixeira A, Goldsmith-Pestana K, Maher S, Hwa J, Krause D, McMahon-Pratt D. Cutaneous leishmaniasis is regulated by Wnt antagonist Dkk-1 from activated platelets (MPF7P.715). The Journal Of Immunology 2015, 194: 203.16-203.16. DOI: 10.4049/jimmunol.194.supp.203.16.Peer-Reviewed Original ResearchConceptsNeutrophil-platelet aggregate formationDkk-1Cutaneous leishmaniasisLate inflammatory responseSkin inflammatory diseasesT cell differentiationMajor infectionAntigen exposureLymph nodesChronic inflammationTh2 cytokinesInflammatory diseasesInflammatory responseTh2 cellsSkin lesionsSmall molecule inhibitorsParasite burdenGATA-3Functional inhibitionMarked inhibitionLeishmaniasisC-MafHuman plateletsMolecule inhibitorsPlatelets
2014
The Immunotherapeutic Role of Regulatory T Cells in Leishmania (Viannia) panamensis Infection
Ehrlich A, Castilho TM, Goldsmith-Pestana K, Chae WJ, Bothwell AL, Sparwasser T, McMahon-Pratt D. The Immunotherapeutic Role of Regulatory T Cells in Leishmania (Viannia) panamensis Infection. The Journal Of Immunology 2014, 193: 2961-2970. PMID: 25098291, PMCID: PMC4170189, DOI: 10.4049/jimmunol.1400728.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsMeSH KeywordsAnimalsAntibodiesAntigen-Antibody ComplexCell ProliferationFemaleImmunotherapy, AdoptiveIndoleamine-Pyrrole 2,3,-DioxygenaseInflammationInterferon-gammaInterleukin-10Interleukin-13Interleukin-17Interleukin-2Leishmania guyanensisLeishmaniasis, MucocutaneousLymphocyte CountMiceMice, Inbred BALB CMice, TransgenicParasite LoadT-Lymphocytes, RegulatoryTransforming Growth Factor betaConceptsRegulatory T cellsPanamensis infectionInflammatory responseT cellsLeishmania parasitesDisease pathologyImmunotherapeutic treatment approachesL. panamensis infectionsLeishmania panamensis infectionPercentage of TregsRIL-2/Th2 inflammatory responseIL-13 levelsParasite loadAlternate treatment strategiesT cell proliferationTreg functionalityDisease exacerbationAdoptive transferIL-17IL-10Naive miceCytokine responsesImmunotherapeutic roleCytokine production
Academic Achievements and Community Involvement
activity Member
CommitteesWHO/T.D.R. Review of Leishmaniasis ProgramDetails2004 - Presentactivity Member
Peer Review Groups and Grant Study SectionsServed as a reviewer for grant applications to the National Science Foundation, Canadian Research Foundation, Veterans Administration and World Health Organization and US Army Research, Wellcome Trust (England)Details1990 - Presentactivity Member
CommitteesProvost’s Appointments and Promotions Committee of EPHactivity Vector/Host-Parasite Interface of Leishmaniasis in Colombia
ResearchDetails01/05/2004 - 12/31/2018Cali, Valle del Cauca, ColombiaAbstract/SynopsisThe goal of the training grant is to build research capacity to identify strategies and devise means to interrupt the cycle of transmission and pathogenesis of leishmaniasis through intervention of the invertebrate and vertebrate host pathogen interactions. To achieve this goal, the training program will implement research capacity in the molecular analysis of the interaction between Leishmania and both the sandfly vector and the mammalian host. The proposed program builds upon the existing research capacity and ongoing projects of the developing country institution in clinical, epidemiological and biological aspects of cutaneous and visceral leishmaniasis and other transmissible diseases, prior collaboration with Yale faculty, and the critical mass of faculty and infrastructure for the conduct of molecular analyses of kinetoplastid parasites and host responses available at Yale University. Colombian scientists will receive training at Yale through the conduct of mentored research, auditing of postgraduate courses and short courses on research skills, such as biosafety, responsible conduct of research, and scientific writing. Workshops will be offered each year at CIDEIM with the participation of Yale Faculty (on site and teleconferencing) to build and multiply research skills and introduce national investigators to concepts and principles of molecular analysis (bioinformatics and data mining, functional genomics, expression analysis). Predoctoral trainees will be selected among postgraduate students from Colombian universities who conduct thesis research in CIDEIM. Students will be recent graduates of human or veterinary medicine and basic science who have qualified for scholarship support within the framework of COLCIENCIAS' Young Investigator program. Post-doctoral training and scientific exchange for periods of up to 4 months will be available to research staff of CIDEIM whose research is relevant to the vector or host- Leishmania interaction. During year 5 of the program, formal postgraduate courses on the molecular genetic analyses of host (mammalian/vector)-pamsite interactions will be offered to national and regional students by CIDEIM. Overall, the training conducted will prepare investigators in new areas of research, implement training by teleconferencing, and assure the capacity to offer formal courses for Colombian and regional post-graduate students. All of these will contribute to the sustainability of research capacity.
activity Member
Professional OrganizationsWorld LEISH 6International meeting on leishmaniasis - Organizing CommitteeDetails09/01/2015 - 05/16/2017