Roman Zubarev Group

The Roman Zubarev group focuses on Molecular Biometry using mass spectrometry for studying various processes of biological and medical importance.

Special research interests beyond Proteomics

Immunology

We have developed a monocyte-based proteomics assay to quantify the innate immune response to xenomolecules and used it to characterize the toxicity of various nanoparticles.

We have also pioneered “SpotLight proteomics” which is based on de novo sequencing of the repertoire of antibody motifs present in blood of a patient cohort.

Gas-phase fragmentation

Roman Zubarev is one of the pioneers of electron capture dissociation (ECD) and related ion-electron reactions. He discovered that organic radicals come in two kinds, hydrogen-abundant and hydrogen-deficient radicals, which differ significantly in their reactivity and properties.

Fasmatech (Athens, Greece) built the ultimate device for gas-phase structural analysis of polypeptides for us – the OMNI-trap. With this device, the decades-old dream of the “top-down” sequencing of large proteins may come true.

Isospartyl in Alzheimer’s disease (AD), ageing and stemness

We formulated the isoaspartate (isoAsp) hypothesis of the AD origin, that postulates that deamidation of asparagyl residue and isomerization of aspartyl residues in proteins initiate the cascade of protein aggregation, ultimately resulting in AD, but also playing an important role in ageing.

We are studying ways to:

  1. measure the isoAsp content in human blood as an AD risk factor,
  2. reduce the isoAsp load in the organism to prevent AD and slow down ageing,
  3. study the role of isoAsp repair in stemness.

Cancer and cell death modalities

Cell morphology measured at the molecular level via abundant, structural proteins can faithfully reflect the behavior of drug targets.

Based on this finding, we are identifying all possible types of cell death by treating cancer cells with a variety of anticancer agents (work in progress).

Origin of life and Astrobiology

We have shown that abiotically produced (from simple gases and water) organic matter can support life of prokaryotes, supporting the idea that early Earth was a hospitable place for primitive life.

For the first time, a living cell was produced from dead matter.

Effect of stable isotopes on biology: Isotopic resonance hypothesis

We have discovered that the average terrestrial isotopic compositions of the elements C, H, N and O are not random but correspond to a “resonance” for molecules with Z=0, where Z = C – (N+H)/2. At an isotopic resonance, a reduction of complexity occurs, and most reactions acquire faster kinetics. Among the molecules with Z=0, 11 out of 20 amino acid residues, and many proteins.

The isotopic resonance hypothesis has been extensively tested and found truthful at p<10-15 level. Therefore, life on Earth has benefitted in early days, and continues to benefit now, by the presence of the Z=0 isotopic resonance. In contrast, neither Mars nor Venus have isotopic resonances. In general, isotopic compositions on Mars are found to be detrimental for terrestrial life.

We continue to explore the isotopic resonance phenomenon and its consequences for biology, medicine and technology.

Staff

Juan Astorga-WellsAssociated
Alexandra BernadotteAssociated
Christian BeuschAssociated
Alexey ChernobrovkinPostdoc
Luciano Di StefanoScholar
Massimiliano GaetaniProject coordinator
Mohsen GhasemiAssociated
Susanna LundströmSenior research specialist
Aleksandr ManoilovAssociated
Carina PalmbergBiomedical scientist
Sergey RodinSenior researcher
Pierre SabatierPhD student, R&D trainee
Amirata Saei DibavarResearch assistant on study grant
Marie StåhlbergBiomedical scientist
Alexander TonevitskyAssociated
Xuepei ZhangAssociated
Roman ZubarevProfessor

Contact

Professor

Roman Zubarev

Phone: +46-(0)8-524 875 94
Organizational unit: Roman Zubarev's group
E-mail: Roman.Zubarev@ki.se

Visiting address

Selected publications

Covariation of Peptide Abundances Accurately Reflects Protein Concentration Differences.
Zhang B, Pirmoradian M, Zubarev R, Käll L
Mol. Cell Proteomics 2017 May;16(5):936-948

Self-assembly of Deinococcus radiodurans supports nanocell scenario of life origin.
Bernadotte A, Semenova V, Musial VAM, Kasprzykowska A, Zubarev RA
Discoveries 2017, Jan-Mar; 5(1):e72

Cytotoxic and Proinflammatory Effects of Metal-Based Nanoparticles on THP-1 Monocytes Characterized by Combined Proteomics Approaches.
Tarasova N, Gallud A, Ytterberg A, Chernobrovkin A, Aranzaes J, Astruc D, et al
J. Proteome Res. 2017 Feb;16(2):689-697

SpotLight Proteomics: uncovering the hidden blood proteome improves diagnostic power of proteomics.
Lundström S, Zhang B, Rutishauser D, Aarsland D, Zubarev R
Sci Rep 2017 Feb;7():41929

On the Effect of Planetary Stable Isotope Compositions on Growth and Survival of Terrestrial Organisms.
Xie X, Zubarev R
PLoS ONE 2017 ;12(1):e0169296

How well can morphology assess cell death modality? A proteomics study.
Chernobrovkin A, Zubarev R
Cell Death Discov ;2():16068

Establishing a Proteomics-Based Monocyte Assay To Assess Differential Innate Immune Activation Responses.
Tarasova N, Ytterberg A, Lundberg K, Zhang X, Harris R, Zubarev R
J. Proteome Res. 2016 Jul;15(7):2337-45

Isoelectric point region pI≈7.4 as a treasure island of abnormal proteoforms in blood
Pirmoradian M, Aarsland D, Zubarev RA
Discoveries 2016, Jul-Sep; 4(4):e67

DeMix-Q: Quantification-Centered Data Processing Workflow.
Zhang B, Käll L, Zubarev R
Mol. Cell Proteomics 2016 Apr;15(4):1467-78

Multijunction Capillary Isoelectric Focusing Device Combined with Online Membrane-Assisted Buffer Exchanger Enables Isoelectric Point Fractionation of Intact Human Plasma Proteins for Biomarker Discovery.
Pirmoradian M, Astorga-Wells J, Zubarev R
Anal. Chem. 2015 Dec;87(23):11840-6

Primordial soup was edible: abiotically produced Miller-Urey mixture supports bacterial growth.
Xie X, Backman D, Lebedev A, Artaev V, Jiang L, Ilag L, et al
Sci Rep 2015 Sep;5():14338

Functional Identification of Target by Expression Proteomics (FITExP) reveals protein targets and highlights mechanisms of action of small molecule drugs.
Chernobrovkin A, Marin-Vicente C, Visa N, Zubarev R
Sci Rep 2015 Jun;5():11176

Isotopic resonance hypothesis: experimental verification by Escherichia coli growth measurements.
Xie X, Zubarev R
Sci Rep 2015 Mar;5():9215

Prognostic polypeptide blood plasma biomarkers of Alzheimer's disease progression.
Yang H, Lyutvinskiy Y, Herukka S, Soininen H, Rutishauser D, Zubarev R
J. Alzheimers Dis. 2014 ;40(3):659-66

In silico instrumental response correction improves precision of label-free proteomics and accuracy of proteomics-based predictive models.
Lyutvinskiy Y, Yang H, Rutishauser D, Zubarev R
Mol. Cell Proteomics 2013 Aug;12(8):2324-31

Peptide Radical Cations: Gender Determines Dissociation Chemistry. Mass Spectrometry.
Zubarev R
Mass Spectrometry 2013;2(Spec Iss):S0004

Alzheimer's disease and mild cognitive impairment are associated with elevated levels of isoaspartyl residues in blood plasma proteins.
Yang H, Lyutvinskiy Y, Soininen H, Zubarev R
J. Alzheimers Dis. 2011 ;27(1):113-8

Early life relict feature in peptide mass distribution
Zubarev R, Artemenko K, Zubarev A, Mayrhofer C, Yang H, Fung Y
Open Life Sciences 2010, 5(2):190-196

Electron ionization dissociation of singly and multiply charged peptides.
Fung Y, Adams C, Zubarev R
J. Am. Chem. Soc. 2009 Jul;131(29):9977-85

Reactions of polypeptide ions with electrons in the gas phase.
Zubarev R
Mass Spectrom Rev ;22(1):57-77

Automated de novo sequencing of proteins by tandem high-resolution mass spectrometry.
Horn D, Zubarev R, McLafferty F
Proc. Natl. Acad. Sci. U.S.A. 2000 Sep;97(19):10313-7

Electron capture dissociation for structural characterization of multiply charged protein cations.
Zubarev R, Horn D, Fridriksson E, Kelleher N, Kruger N, Lewis M, et al
Anal. Chem. 2000 Feb;72(3):563-73