Vincent Marchesi, MD, PhD
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Anthony N. Brady Professor Emeritus of Pathology
Director, Boyer Center for Molecular MedicineBiography
I am a graduate of Yale College (BA 1957), Oxford University (D.Phil.1961)
and the Yale School of Medicine (MD, 1963). I trained in anatomical
pathology at Washington University (1963-65), spent a post-doctoral year at
Rockefeller University with George Palade, and served in the USPHS at the
NIH from1966 to 1972.
I was recruited to Yale by Lewis Thomas in 1972, and a
year later was named the Anthony N. Brady Professor of pathology and chair
of the department and Pathologist-in-Chief of the Yale New Haven Hospital.
In 1991 I became the Director of the Boyer Center for Molecular Medicine. I
am a member of the National Academy of Sciences and the Institute of
Medicine.
Appointments
Pathology
EmeritusPrimary
Other Departments & Organizations
Education & Training
- MD
- Yale University School of Medicine (1963)
- PhD
- Oxford University (1961)
- BA
- Yale University (1957)
Research
Overview
Alzheimer’s dementia is the result of a cascade of
pathological processes that work
in concert over many decades to reduce the number of functioning neurons of the
human brain that are responsible
for memory and other executive actions. Neuronal cell death is believed
to be due to the accumulation of potentially toxic amyloid related peptides,
referred to as Abeta 40 and 42, through either their excessive production or
reduced clearance. Amyloid
deposits can be removed from animal and human brains by specific
antibody treatments, and clinical trials using this approach are now under way. Antibodies
to fragments of amyloid abeta peptides are now recognized as biological agents
with great therapeutic potential.
Two recent reports present evidence that naturally occurring auto-antibodies to abeta might be neuro-protective. In one study auto-antibodies to an aggregated form of abeta were found to be depressed in AD patients, but, paradoxically, elevated in normal, young adults. A second report describes a decrease in the incidence of AD in people treated with intravenous immunoglobulin preparations Both results are consistent with the idea that natural antibodies to abeta exist in all people and are depleted in advanced AD.
Contrary to these results, we have found that there is no clear correlation with levels of anti-abeta antibodies and the clinical status of the donor. Antibodies to a peptide fragment (p16-34) of abeta are elevated in many but not all individuals with advanced AD. We have found that intravenous immunoglobulin preparations also react with the p16-34 abeta fragment. If naturally occurring antibodies to abeta are indeed neuro-protective, as the available evidence suggests, it will be important to determine which epitopes of abeta induce the protective response, and, equally important, to identify the epitopes that might confer toxicity. The patho-physiological significance of auto-antibodies to amyloid abeta peptides is clearly a complicated question that deserves further study. auto-antibodies to amyloid abeta peptides
neuro-protective antibodies
Two recent reports present evidence that naturally occurring auto-antibodies to abeta might be neuro-protective. In one study auto-antibodies to an aggregated form of abeta were found to be depressed in AD patients, but, paradoxically, elevated in normal, young adults. A second report describes a decrease in the incidence of AD in people treated with intravenous immunoglobulin preparations Both results are consistent with the idea that natural antibodies to abeta exist in all people and are depleted in advanced AD.
Contrary to these results, we have found that there is no clear correlation with levels of anti-abeta antibodies and the clinical status of the donor. Antibodies to a peptide fragment (p16-34) of abeta are elevated in many but not all individuals with advanced AD. We have found that intravenous immunoglobulin preparations also react with the p16-34 abeta fragment. If naturally occurring antibodies to abeta are indeed neuro-protective, as the available evidence suggests, it will be important to determine which epitopes of abeta induce the protective response, and, equally important, to identify the epitopes that might confer toxicity. The patho-physiological significance of auto-antibodies to amyloid abeta peptides is clearly a complicated question that deserves further study. auto-antibodies to amyloid abeta peptides
neuro-protective antibodies
Medical Subject Headings (MeSH)
Alzheimer Disease; Autoantibodies; Cell Biology; Pathology; Protein Folding
Research at a Glance
Publications Timeline
A big-picture view of Vincent Marchesi's research output by year.
41Publications
2,300Citations
Publications
2008
The Relevance of Research on Red Cell Membranes to the Understanding of Complex Human Disease: A Personal Perspective
Marchesi VT. The Relevance of Research on Red Cell Membranes to the Understanding of Complex Human Disease: A Personal Perspective. Annual Review Of Pathology Mechanisms Of Disease 2008, 3: 1-9. PMID: 18039128, DOI: 10.1146/annurev.pathmechdis.3.121806.154321.Peer-Reviewed Original ResearchCitationsMeSH Keywords and ConceptsConceptsCell membrane proteinsMembrane proteinsHuman cell membrane proteinsHuman diseasesRed blood cell membrane proteinsComplex human diseasesMolecular biological studiesRed cell membraneRecombinant DNAMolecular analysisCell membraneHuman erythrocyte membranesService of researchBiological studiesProteinErythrocyte membranesMembrane
2005
An alternative interpretation of the amyloid Aβ hypothesis with regard to the pathogenesis of Alzheimer's disease
Marchesi VT. An alternative interpretation of the amyloid Aβ hypothesis with regard to the pathogenesis of Alzheimer's disease. Proceedings Of The National Academy Of Sciences Of The United States Of America 2005, 102: 9093-9098. PMID: 15967987, PMCID: PMC1166615, DOI: 10.1073/pnas.0503181102.Peer-Reviewed Original ResearchCitationsMeSH KeywordsAmino Acid MotifsAmino Acid SequenceAmyloid beta-PeptidesAmyloid beta-Protein PrecursorAmyloid Precursor Protein SecretasesCell MembraneCentral Nervous SystemDimerizationEndopeptidasesHumansLipid BilayersMembrane GlycoproteinsMembrane ProteinsModels, BiologicalMolecular Sequence DataNeuronsPeptide HydrolasesPeptidesPresenilin-1Protein BindingSequence Homology, Amino AcidSodium Dodecyl SulfateTemperature
1998
www.fasebj.org
Marchesi V. www.fasebj.org. The FASEB Journal 1998, 12: 1253-1253. PMID: 9761769, DOI: 10.1096/fasebj.12.13.1253.Peer-Reviewed Original ResearchCitationsFrom Molecular Analysis to Medical Practice: Recent Studies Reveal New Therapeutic Targets for an Old Medicine
Marchesi V. From Molecular Analysis to Medical Practice: Recent Studies Reveal New Therapeutic Targets for an Old Medicine. The FASEB Journal 1998, 12: 1061-1061. PMID: 9737709, DOI: 10.1096/fasebj.12.12.1061.Peer-Reviewed Original ResearchCitationsMeSH Keywords and ConceptsHard Days … on the Endless Frontier? … or in the Trenches?
Marchesi V. Hard Days … on the Endless Frontier? … or in the Trenches? The FASEB Journal 1998, 12: 253-253. PMID: 9506464, DOI: 10.1096/fasebj.12.3.253.Peer-Reviewed Original ResearchMeSH Keywords“According to the definition of intellectual property,” Mario Biagioli notes, “a scientist is literally a non-author.”
Marchesi V. “According to the definition of intellectual property,” Mario Biagioli notes, “a scientist is literally a non-author.”. The FASEB Journal 1998, 12: 1-1. DOI: 10.1096/fasebj.12.1.1.Peer-Reviewed Original ResearchCitationsConcepts“According to the definition of intellectual property,” Mario Biagioli notes, “a scientist is literally a non‐author.”
Marchesi V. “According to the definition of intellectual property,” Mario Biagioli notes, “a scientist is literally a non‐author.”. The FASEB Journal 1998, 12: 1-1. DOI: 10.1096/fsb2fasebj.12.1.1.Peer-Reviewed Original ResearchConcepts
1996
The Life Sciences Forum–A Call for Contributions
Marchesi V. The Life Sciences Forum–A Call for Contributions. The FASEB Journal 1996, 10: 1111-1111. PMID: 8751712, DOI: 10.1096/fasebj.10.10.8751712.Peer-Reviewed Original Research
1995
Yale’s Boyer Center for Molecular Medicine
Marchesi V. Yale’s Boyer Center for Molecular Medicine. Molecular Medicine 1995, 1: 477-478. PMID: 8529113, PMCID: PMC2229965, DOI: 10.1007/bf03401584.Peer-Reviewed Original Research
1993
In vitro assembly of multiprotein complexes containing alpha, beta, and gamma tubulin, heat shock protein HSP70, and elongation factor 1 alpha.
Marchesi V, Ngo N. In vitro assembly of multiprotein complexes containing alpha, beta, and gamma tubulin, heat shock protein HSP70, and elongation factor 1 alpha. Proceedings Of The National Academy Of Sciences Of The United States Of America 1993, 90: 3028-3032. PMID: 8464918, PMCID: PMC46230, DOI: 10.1073/pnas.90.7.3028.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsMeSH KeywordsAnimalsCentrifugation, Density GradientCHO CellsCricetinaeElectrophoresis, Polyacrylamide GelHeat-Shock ProteinsHeLa CellsHumansImmunoblottingMacromolecular SubstancesMitosisModels, StructuralMolecular WeightNocodazolePeptide Elongation Factor 1Peptide Elongation FactorsRibonucleoproteinsTubulinConceptsElongation factor 1 alphaHeat shock protein Hsp70Multiprotein complexesShock protein Hsp70Factor 1 alphaGamma-tubulinProtein Hsp70Regulation of mitosisPresence of ATPDistinct complexesMitotic centrosomesActin isoformsSucrose gradient ultracentrifugationVitro assemblyTubulin isoformsLow abundanceCHO cellsHSP70Degrees C incubationProteinCognate formIsoformsSmall precursorsHigh-speed centrifugationComplexes
Academic Achievements and Community Involvement
honor National Academy of Sciences
National AwardDetails07/01/1988United Stateshonor Institute of Medicine
National AwardDetails07/01/1988United States
Links & Media
News
- April 15, 2007
A clear solution to a protein puzzle
- March 01, 2007
A crystal-clear look at a puzzling protein
- September 15, 2001
For 500 alumni and their guests, a return to New Haven
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