Jorge Galán, PhD, DVM
Cards
Appointments
Contact Info
Microbial Pathogenesis
Boyer Center for Molecular Medicine, 295 Congress Av.
New Haven, CT 06536-0812
United States
About
Titles
Lucille P. Markey Professor of Microbial Pathogenesis and Professor of Cell Biology
Biography
Dr. Jorge E. Galán earned his DVM from the National University of La Plata (Argentina) and his Ph.D. in Microbiology from Cornell University. He completed postdoctoral studies at Washington University in St. Louis, and was in the Faculty at SUNY Stony Brook before coming to Yale in 1998. He is currently the Lucille B. Markey Professor of Microbiology and Professor of Cell Biology at the Yale University School of Medicine. Dr. Galán is the recipient of numerous honors and awards including the Pew Scholar in Biomedical Sciences, the Searle Scholar Award, the National Institutes of Health MERIT award in 2000 and 2015, the Hans Sigrist Prize, the Alexander M. Cruickshank Award, and the Robert Koch Prize. He is a member of the American Academy of Microbiology, the German Academy of Sciences Leopoldina, a fellow of the American Association for the Advancement of Sciences, and a member of the USA National Academy of Science and the USA National Academy of Medicine. He is a member of several Scientific Advisory Boards and has authored more than 200 publications in the field of bacterial pathogenesis and molecular biology.
Appointments
Microbial Pathogenesis
ProfessorPrimaryCell Biology
ProfessorSecondary
Other Departments & Organizations
Education & Training
- Postdoctoral fellow
- Washington University (1990)
- PhD
- Cornell University (1986)
- DVM
- National University of La Plata (1980)
Research
Overview
Microbial pathogens have evolved unique ways to interact with their hosts. In many instances the terms of this interaction reflect the co-evolutionary balance that the host and pathogen must reach in order to secure
their survival. It is therefore not surprising that bacterial pathogens have evolved a large array of virulence
factors well suited to interfere with or stimulate a variety of host-cell responses in order to invade, survive and replicate within their hosts. The identification and characterization of these virulence factors is proving to be a fruitful area of research in more ways than expected.
The understanding of how pathogens interact with their hosts is not only providing the basis for the development of novel therapeutic approaches but also a number of very sophisticated tools for probing basic aspects of cellular physiology and immunology. Our laboratory studies the pathogenesis of two intestinal pathogens, Salmonella enterica and Campylobacter jejuni. Combined, these two pathogens account for the vast majority of cases of infectious diarrhea world-wide leading to an estimated 2,000,000 deads. We are interested in characterizing the bacterial determinants involved in these interactions as well as the cell biology and immunobiology of this process.
We take a multidisciplinary approach in our studies involving bacterial genetics, biochemistry, cell biology, immunology as well as structural biology. As a result, we are beginning to define not only the molecular details of the host pathogen interactions but also the atomic interphase between these pathogens and the host. Our laboratory has also an interest in vaccine development that stems from our discovery of a specialized organelle in Salmonella enterica (the “type III secretion system”) that mediates the transfer of bacterial proteins into host cells. We have harnessed this system for the delivery of heterologous proteins as a means to delivery antigens to the Class I and Class II antigen presenting pathways by avirulent strains of Salmonella.
Specific areas of interest include:
- The study of type III protein secretion machines, specialized bacterial organelles whose function is to delivery bacterial proteins into eukaryotic host cells. We are interested in understanding the mechanism of action of this multi-protein machine, as well as to understand the activities of the effector proteins delivered by this machine. We carried out these studies in Salmonella enterica but it is expected that knowledge gained from these studies may help understand the pathogenesis of many other bacteria since this system is conserved and widespread among several important pathogens.
- The harnessing of the protein-delivery capability of the type III secretion machine for the development of therapeutic approaches, including vaccines.
- The development of strategies that target the activities of type III secretion systems with the ultimate goal of developing new therapeutics to combat diseases caused by pathogens that encode these protein-delivery machines.
- The study the mechanism of pathogenesis of Salmonella typhi, which causes typhoid fever in humans, a life-threatening disease that causes more than 200,000 deaths world-wide. We focus our efforts on the study of "typhoid toxin", a toxin exclusively produced by Salmonella typhi that we recently identified and it is central for the pathogenesis of typhoid fever.
- The study of the mechanisms by which Campylobacter jejuni is able to colonize the gut and the role of the intestinal microbiota in both, facilitating and preventing colonization.
- The investigation of the in vivo metabolism of C. jejuni. We are specifically interested in identifying its carbon sources and respiration substrates during infection and the contribution of the intestinal microbiota in providing those nutrients.
Medical Subject Headings (MeSH)
Research at a Glance
Yale Co-Authors
Publications Timeline
Research Interests
Mark Mooseker, PhD
Fulan Guan, PhD
María Lara-Tejero, DVM, PhD
Nigel Grindley, PhD
Salmonella
Type III Secretion Systems
Cryoelectron Microscopy
Immunity, Innate
Inflammation
Microscopy, Fluorescence
Publications
2024
Loss of function of metabolic traits in typhoidal Salmonella without apparent genome degradation
Machado L, Galán J. Loss of function of metabolic traits in typhoidal Salmonella without apparent genome degradation. MBio 2024, 15: e00607-24. PMID: 38572992, PMCID: PMC11077982, DOI: 10.1128/mbio.00607-24.Peer-Reviewed Original ResearchMeSH Keywords and ConceptsConceptsSalmonella enterica</i> serovar TyphiAdaptive convergent evolutionFunction of metabolic pathwaysAmino acid substitutionsConvergent evolutionMetabolic pathwaysParatyphi A.Paratyphi AHuman hostTranscriptional regulationAcid substitutionsMetabolic capabilitiesPoint mutationsParatyphoid feverTranscriptional regulatory proteinsMetabolic enzymesAffecting different genesPresence of point mutationsGenome degradationTyphoidal SalmonellaGlucose-6-phosphateCoding sequenceBioinformatics approachTyphiBacterial pathogens
2023
Parkinson’s disease kinase LRRK2 coordinates a cell-intrinsic itaconate-dependent defence pathway against intracellular Salmonella
Lian H, Park D, Chen M, Schueder F, Lara-Tejero M, Liu J, Galán J. Parkinson’s disease kinase LRRK2 coordinates a cell-intrinsic itaconate-dependent defence pathway against intracellular Salmonella. Nature Microbiology 2023, 8: 1880-1895. PMID: 37640963, PMCID: PMC10962312, DOI: 10.1038/s41564-023-01459-y.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsLeucine-rich repeat kinase 2Loss of LRRK2Host defense mechanismsKinase leucine-rich repeat kinase 2Parkinson's disease-associated leucine-rich repeat kinase 2Host defense pathwaysBacterial pathogen SalmonellaRepeat kinase 2Salmonella infectionSalmonella-containing vacuolesCell-intrinsic defenseIntracellular pathogensIntracellular SalmonellaFirst lineSalmonella replicationSalmonella mutantsKinase 2Pathogen SalmonellaDefense mechanismsSalmonellaHost mitochondriaDefense pathwaysDeliveryDefense responsesCells
2022
Assembly and architecture of the type III secretion sorting platform
Soto J, Galán J, Lara-Tejero M. Assembly and architecture of the type III secretion sorting platform. Proceedings Of The National Academy Of Sciences Of The United States Of America 2022, 119: e2218010119. PMID: 36512499, PMCID: PMC9907115, DOI: 10.1073/pnas.2218010119.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsType III secretion machinesType III secretion systemTarget eukaryotic cellsType III secretionSecretion of proteinsBacterial nanomachinesSecretion machineEukaryotic cellsExport pathwayImportant bacterial pathogensSecretion systemBacterial structureAntivirulence strategiesCoordinated mechanismFunctional complexityBacterial pathogensGenetic deletionStructure modelingProtein deliveryAssemblyRational developmentCross-linking strategyAssembly processProteinDeletionTyphoid toxin sorting and exocytic transport from Salmonella Typhi-infected cells
Chang SJ, Hsu YT, Chen Y, Lin YY, Lara-Tejero M, Galan JE. Typhoid toxin sorting and exocytic transport from Salmonella Typhi-infected cells. ELife 2022, 11: e78561. PMID: 35579416, PMCID: PMC9142146, DOI: 10.7554/elife.78561.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsCellular machineryType III protein secretion systemSpecific cellular machineryVesicle carriersProtein secretion systemExtracellular spaceTyphoid toxinEssential virulence factorExocytic transportGTPase Sar1Syntaxin 4Unusual biologySecretion systemPlasma membraneIntracellular transportRemarkable adaptationSpecific effectorsHost cellsIntracellular pathogensVirulence factorsMachineryCooptionVacuolesToxinSpecific environment
2019
The Injectisome, a Complex Nanomachine for Protein Injection into Mammalian Cells
Lara-tejero M, Galán J. The Injectisome, a Complex Nanomachine for Protein Injection into Mammalian Cells. 2019, 245-259. DOI: 10.1128/9781683670285.ch20.Peer-Reviewed Original ResearchCitationsConceptsSecretion machineType III protein secretion systemType III secretion machinesProtein secretion systemTarget eukaryotic cellsCell biological processesType III systemMultiprotein nanomachineEukaryotic hostsComplex nanomachinesGram-negative bacteriaPlant pathogensSymbiotic interactionsEukaryotic cellsEffector proteinsSecretion systemMammalian cellsImportant humanBiological processesStructural organizationInjectisomeBacteriaCurrent knowledgeCentral rolePrimary function
2016
Antibacterial Flavonoids from Medicinal Plants Covalently Inactivate Type III Protein Secretion Substrates
Tsou LK, Lara-Tejero M, RoseFigura J, Zhang ZJ, Wang YC, Yount JS, Lefebre M, Dossa PD, Kato J, Guan F, Lam W, Cheng YC, Galán J, Hang HC. Antibacterial Flavonoids from Medicinal Plants Covalently Inactivate Type III Protein Secretion Substrates. Journal Of The American Chemical Society 2016, 138: 2209-2218. PMID: 26847396, PMCID: PMC4831573, DOI: 10.1021/jacs.5b11575.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsVirulence pathwaysType III protein secretionType III secretion system effectorsSpecific plant metabolitesSPI-1 T3SSSecretion system effectorsS. typhimurium invasionSalmonella enterica serovar TyphimuriumSecretion substratesEnterica serovar TyphimuriumTraditional Chinese medicineUnappreciated mechanismPlant metabolitesTyphimurium invasionProtein secretionSerovar TyphimuriumAntibacterial flavonoidsBacterial invasionEpithelial cellsSpecific flavonoidsBacterial growthMedicinal plantsPathwayPotential mechanismsInvasion
2015
9 Typhoid toxin
Galan J. 9 Typhoid toxin. 2015, 261-266. DOI: 10.1016/b978-0-12-800188-2.00009-4.Peer-Reviewed Original ResearchConceptsTyphoid feverTyphoid toxinLife-threatening systemic diseaseUnique virulence factorsSalmonella enterica serovar TyphiPentameric B subunitEnterica serovar TyphiSystemic diseaseExperimental animalsFeverUnique receptorSerovar TyphiVirulence factorsToxinDiseaseB subunitSalmonella entericaPathogenesisSymptomsSpecificityHuman glycansImportant diseaseReceptors
2008
Interaction of Campylobacter jejuni with Host Cells
Watson R, Galán J. Interaction of Campylobacter jejuni with Host Cells. 2008, 287-296. DOI: 10.1128/9781555815554.ch16.Peer-Reviewed Original ResearchCitationsConceptsHost cellsBacterial internalizationCell biologyHost cell gene expressionVesicular trafficking pathwaysPowerful genetic toolsCell gene expressionEndocytic machineryTrafficking pathwaysStrong phenotypeGenetic toolsCampylobacter jejuniJejuni mutantsGene expressionIntestinal epithelial cellsMicrobial pathogensInnate immune responseNonphagocytic cellsOwn uptakeBacterial determinantsSpecific adaptationsIntracellular pathogensMutantsPathogenic bacteriaCell interactionsModulation of the actin cytoskeleton by Salmonella
Galan J. Modulation of the actin cytoskeleton by Salmonella. The FASEB Journal 2008, 22: 530.1-530.1. DOI: 10.1096/fasebj.22.1_supplement.530.1.Peer-Reviewed Original ResearchConceptsEffector proteinsHost cellsActin cytoskeletonBacterial proteinsCellular responsesBacterial effector proteinsProtein secretion systemSpecialized protein secretion systemActin cytoskeletal reorganizationDownstream effector proteinsSignal transduction pathwaysProtein Cdc42Exchange factorMembrane rufflingSmall GTPRho GTPasesSecretion systemCytoskeletal reorganizationTransduction pathwaysCytoskeletal rearrangementsCdc42RhoG.ProteinCytoskeletonRac
2007
Structure, assembly and function of the Salmonella type III protein secretion organelle
Galán J. Structure, assembly and function of the Salmonella type III protein secretion organelle. GBM Fall Meeting Hamburg 2007 2007, 2007 DOI: 10.1240/sav_gbm_2007_h_002101.Peer-Reviewed Original Research
Academic Achievements and Community Involvement
activity Advisor
Peer Review Groups and Grant Study SectionsBiomed CentralDetails2000 - PresentDescriptionEditorial Boardactivity Coordinator
Professional OrganizationsCold Spring Harbor LaboratoriesDetails2001 - PresentDescriptionBanbury Conference on Microbial Pathogenesisactivity Chairperson
Professional OrganizationsGordon ConferencesDetails2001 - PresentDescriptionGordon Conference on Microbial Adhesion and Signal Transductionactivity Member
Peer Review Groups and Grant Study SectionsCell Host & MicrobeDetails2006 - PresentDescriptionEditorial Boardactivity Advisory Board
ResearchDetails01/01/2013 - 11/01/2021Santiago, Santiago Metropolitan Region, ChileAbstract/SynopsisMember, Scientific Advisory Board, Millenium Science Initiative, Gobierno de Chile.
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The type III protein secretion machine
The type III protein secretion machine visualized at different resolution scales
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Microbial Pathogenesis
Boyer Center for Molecular Medicine, 295 Congress Av.
New Haven, CT 06536-0812
United States