skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: The role of proteomics in assessing beta-cell dysfunction and death in type 1 diabetes

Abstract

Introduction: Type 1 diabetes is characterized by autoimmune destruction of the pancreatic beta cells, resulting in the shortage of insulin and inability to control glycemia. Unfortunately, the process of beta-cell death is poorly understood, and the current best treatment for type 1 diabetes is administration of exogenous insulin. To better understand the process of beta-cell death and to develop new therapies for T1D, there is an urgent need for biomarkers that can reliably predict each stage of the disease. Areas covered: Mass spectrometry-based proteomics and complementary techniques are playing an important role in understanding the processes of the autoimmune response, inflammation and beta-cell death. Mass spectrometry is also a leading technology for the identification of biomarkers. This, and the technical difficulties and new technologies that provide opportunities to characterize small amounts of sample in great depth and to analyze large sample cohorts will be discussed in the present review. Expert opinion: Understanding mechanisms of and discovering biomarkers associated with disease development are interconnected processes that depend on each other to be successful. Ideal biomarkers would be molecules specific to the different stages of the disease process that are released from beta cells to the bloodstream. However, such molecules are likelymore » present in trace amounts in the blood due to the small number of pancreatic beta cells in the human body and the heterogeneity of the target organ and disease process. New and better proteomics technologies will play a major role in achieving a better understanding of the disease and in identifying specific and sensitive biomarkers.« less

Authors:
ORCiD logo [1]; ORCiD logo [1];  [2];  [3];  [4]; ORCiD logo [1]
  1. BATTELLE (PACIFIC NW LAB)
  2. Indiana University School of Medicine
  3. Indiana University - Purdue University at Indianapolis
  4. Université Libre de Bruxelles
Publication Date:
Research Org.:
Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
1543305
Report Number(s):
PNNL-SA-142336
DOE Contract Number:  
AC05-76RL01830
Resource Type:
Journal Article
Journal Name:
Expert Review of Proteomics
Additional Journal Information:
Journal Volume: 16; Journal Issue: 7
Country of Publication:
United States
Language:
English

Citation Formats

Nakayasu, Ernesto S., Qian, Weijun, Evans-Molina, Carmella, Mirmira, Raghavendra, Eizirik, Decio L., and Metz, Thomas O. The role of proteomics in assessing beta-cell dysfunction and death in type 1 diabetes. United States: N. p., 2019. Web. doi:10.1080/14789450.2019.1634548.
Nakayasu, Ernesto S., Qian, Weijun, Evans-Molina, Carmella, Mirmira, Raghavendra, Eizirik, Decio L., & Metz, Thomas O. The role of proteomics in assessing beta-cell dysfunction and death in type 1 diabetes. United States. doi:10.1080/14789450.2019.1634548.
Nakayasu, Ernesto S., Qian, Weijun, Evans-Molina, Carmella, Mirmira, Raghavendra, Eizirik, Decio L., and Metz, Thomas O. Wed . "The role of proteomics in assessing beta-cell dysfunction and death in type 1 diabetes". United States. doi:10.1080/14789450.2019.1634548.
@article{osti_1543305,
title = {The role of proteomics in assessing beta-cell dysfunction and death in type 1 diabetes},
author = {Nakayasu, Ernesto S. and Qian, Weijun and Evans-Molina, Carmella and Mirmira, Raghavendra and Eizirik, Decio L. and Metz, Thomas O.},
abstractNote = {Introduction: Type 1 diabetes is characterized by autoimmune destruction of the pancreatic beta cells, resulting in the shortage of insulin and inability to control glycemia. Unfortunately, the process of beta-cell death is poorly understood, and the current best treatment for type 1 diabetes is administration of exogenous insulin. To better understand the process of beta-cell death and to develop new therapies for T1D, there is an urgent need for biomarkers that can reliably predict each stage of the disease. Areas covered: Mass spectrometry-based proteomics and complementary techniques are playing an important role in understanding the processes of the autoimmune response, inflammation and beta-cell death. Mass spectrometry is also a leading technology for the identification of biomarkers. This, and the technical difficulties and new technologies that provide opportunities to characterize small amounts of sample in great depth and to analyze large sample cohorts will be discussed in the present review. Expert opinion: Understanding mechanisms of and discovering biomarkers associated with disease development are interconnected processes that depend on each other to be successful. Ideal biomarkers would be molecules specific to the different stages of the disease process that are released from beta cells to the bloodstream. However, such molecules are likely present in trace amounts in the blood due to the small number of pancreatic beta cells in the human body and the heterogeneity of the target organ and disease process. New and better proteomics technologies will play a major role in achieving a better understanding of the disease and in identifying specific and sensitive biomarkers.},
doi = {10.1080/14789450.2019.1634548},
journal = {Expert Review of Proteomics},
number = 7,
volume = 16,
place = {United States},
year = {2019},
month = {7}
}

Works referenced in this record:

Beta cells in type 1 diabetes: mass and function; sleeping or dead?
journal, February 2019


The role of inflammation in insulitis and β-cell loss in type 1 diabetes
journal, April 2009

  • Eizirik, Décio L.; Colli, Maikel L.; Ortis, Fernanda
  • Nature Reviews Endocrinology, Vol. 5, Issue 4
  • DOI: 10.1038/nrendo.2009.21

Type 1 diabetes
journal, June 2018


Etiology of Type 1 Diabetes
journal, April 2010


Genetic risk factors for type 1 diabetes
journal, June 2016


Estimated Life Expectancy in a Scottish Cohort With Type 1 Diabetes, 2008-2010
journal, January 2015


Life expectancy of type 1 diabetic patients during 1997–2010: a national Australian registry-based cohort study
journal, January 2016


Staging Presymptomatic Type 1 Diabetes: A Scientific Statement of JDRF, the Endocrine Society, and the American Diabetes Association
journal, September 2015

  • Insel, Richard A.; Dunne, Jessica L.; Atkinson, Mark A.
  • Diabetes Care, Vol. 38, Issue 10
  • DOI: 10.2337/dc15-1419

Targeting of memory T cells with alefacept in new-onset type 1 diabetes (T1DAL study): 12 month results of a randomised, double-blind, placebo-controlled phase 2 trial
journal, December 2013


Alefacept provides sustained clinical and immunological effects in new-onset type 1 diabetes patients
journal, July 2015

  • Rigby, Mark R.; Harris, Kristina M.; Pinckney, Ashley
  • Journal of Clinical Investigation, Vol. 125, Issue 8
  • DOI: 10.1172/JCI81722

Low-Dose Anti-Thymocyte Globulin (ATG) Preserves β-Cell Function and Improves HbA 1c in New-Onset Type 1 Diabetes
journal, July 2018

  • Haller, Michael J.; Schatz, Desmond A.; Skyler, Jay S.
  • Diabetes Care, Vol. 41, Issue 9
  • DOI: 10.2337/dc18-0494

Mass-spectrometric exploration of proteome structure and function
journal, September 2016


Stable Isotope Labeling by Amino Acids in Cell Culture, SILAC, as a Simple and Accurate Approach to Expression Proteomics
journal, May 2002

  • Ong, Shao-En; Blagoev, Blagoy; Kratchmarova, Irina
  • Molecular & Cellular Proteomics, Vol. 1, Issue 5
  • DOI: 10.1074/mcp.M200025-MCP200

Isobaric Labeling-Based Relative Quantification in Shotgun Proteomics
journal, November 2014

  • Rauniyar, Navin; Yates, John R.
  • Journal of Proteome Research, Vol. 13, Issue 12
  • DOI: 10.1021/pr500880b

Tools for Label-free Peptide Quantification
journal, December 2012

  • Nahnsen, Sven; Bielow, Chris; Reinert, Knut
  • Molecular & Cellular Proteomics, Vol. 12, Issue 3
  • DOI: 10.1074/mcp.R112.025163

Quantitative mass spectrometry in proteomics: a critical review
journal, August 2007

  • Bantscheff, Marcus; Schirle, Markus; Sweetman, Gavain
  • Analytical and Bioanalytical Chemistry, Vol. 389, Issue 4
  • DOI: 10.1007/s00216-007-1486-6

Advances in targeted proteomics and applications to biomedical research
journal, August 2016


Contributions of immunoaffinity chromatography to deep proteome profiling of human biofluids
journal, May 2016


Combining laser capture microdissection and proteomics: Methodologies and clinical applications
journal, February 2010


Characterization of peptides bound to the class I MHC molecule HLA-A2.1 by mass spectrometry
journal, March 1992


Constitutive and Inflammatory Immunopeptidome of Pancreatic  -Cells
journal, August 2012

  • Dudek, N. L.; Tan, C. T.; Gorasia, D. G.
  • Diabetes, Vol. 61, Issue 11
  • DOI: 10.2337/db11-1333

Conventional and Neo-antigenic Peptides Presented by β Cells Are Targeted by Circulating Naïve CD8+ T Cells in Type 1 Diabetic and Healthy Donors
journal, December 2018

  • Gonzalez-Duque, Sergio; Azoury, Marie Eliane; Colli, Maikel L.
  • Cell Metabolism, Vol. 28, Issue 6
  • DOI: 10.1016/j.cmet.2018.07.007

When one becomes many-Alternative splicing in β-cell function and failure
journal, September 2018

  • Alvelos, Maria Inês; Juan-Mateu, Jonàs; Colli, Maikel Luis
  • Diabetes, Obesity and Metabolism, Vol. 20
  • DOI: 10.1111/dom.13388

Pathogenic CD4 T cells in type 1 diabetes recognize epitopes formed by peptide fusion
journal, February 2016


A roadmap of the generation of neoantigens as targets of the immune system in type 1 diabetes
journal, December 2016


Posttranslational Modification of HLA-DQ Binding Islet Autoantigens in Type 1 Diabetes
journal, October 2013

  • van Lummel, M.; Duinkerken, G.; van Veelen, P. A.
  • Diabetes, Vol. 63, Issue 1
  • DOI: 10.2337/db12-1214

Systematic discovery of regulated and conserved alternative exons in the mammalian brain reveals NMD modulating chromatin regulators
journal, March 2015

  • Yan, Qinghong; Weyn-Vanhentenryck, Sebastien M.; Wu, Jie
  • Proceedings of the National Academy of Sciences, Vol. 112, Issue 11
  • DOI: 10.1073/pnas.1502849112

Alternative isoform regulation in human tissue transcriptomes
journal, November 2008

  • Wang, Eric T.; Sandberg, Rickard; Luo, Shujun
  • Nature, Vol. 456, Issue 7221
  • DOI: 10.1038/nature07509

Peptide splicing by the proteasome
journal, November 2017

  • Vigneron, Nathalie; Ferrari, Violette; Stroobant, Vincent
  • Journal of Biological Chemistry, Vol. 292, Issue 51
  • DOI: 10.1074/jbc.R117.807560

A large fraction of HLA class I ligands are proteasome-generated spliced peptides
journal, October 2016


Identification of Hybrid Insulin Peptides (HIPs) in Mouse and Human Islets by Mass Spectrometry
journal, December 2018


Do post-translational beta cell protein modifications trigger type 1 diabetes?
journal, September 2013

  • Størling, Joachim; Overgaard, Anne Julie; Brorsson, Caroline Anna
  • Diabetologia, Vol. 56, Issue 11
  • DOI: 10.1007/s00125-013-3045-3

Human islets and dendritic cells generate post-translationally modified islet autoantigens: Post-Translational Modification by Human Islets and DC
journal, May 2016

  • McLaughlin, R. J.; de Haan, A.; Zaldumbide, A.
  • Clinical & Experimental Immunology, Vol. 185, Issue 2
  • DOI: 10.1111/cei.12775

PAD, a growing family of citrullinating enzymes: genes, features and involvement in disease
journal, November 2003

  • Vossenaar, Erik R.; Zendman, Albert J. W.; van Venrooij, Walther J.
  • BioEssays, Vol. 25, Issue 11
  • DOI: 10.1002/bies.10357

Citrullinated Glucose-Regulated Protein 78 Is an Autoantigen in Type 1 Diabetes
journal, September 2014

  • Rondas, Dieter; Crèvecoeur, Inne; D’Hertog, Wannes
  • Diabetes, Vol. 64, Issue 2
  • DOI: 10.2337/db14-0621

Inflammation-Induced Citrullinated Glucose-Regulated Protein 78 Elicits Immune Responses in Human Type 1 Diabetes
journal, October 2018

  • Buitinga, Mijke; Callebaut, Aïsha; Marques Câmara Sodré, Fernanda
  • Diabetes, Vol. 67, Issue 11
  • DOI: 10.2337/db18-0295

Interferon-α mediates human beta cell HLA class I overexpression, endoplasmic reticulum stress and apoptosis, three hallmarks of early human type 1 diabetes
journal, January 2017


IFN-α induces a preferential long-lasting expression of MHC class I in human pancreatic beta cells
journal, January 2018

  • Coomans de Brachène, Alexandra; Dos Santos, Reinaldo S.; Marroqui, Laura
  • Diabetologia, Vol. 61, Issue 3
  • DOI: 10.1007/s00125-017-4536-4

PDL1 is expressed in the islets of people with type 1 diabetes and is up-regulated by interferons-α and-γ via IRF1 induction
journal, October 2018


A Comprehensive Analysis of Cytokine-induced and Nuclear Factor-κB-dependent Genes in Primary Rat Pancreatic β-Cells
journal, October 2001

  • Cardozo, Alessandra K.; Heimberg, Harry; Heremans, Yves
  • Journal of Biological Chemistry, Vol. 276, Issue 52
  • DOI: 10.1074/jbc.M108658200

Conditional and specific NF- B blockade protects pancreatic beta cells from diabetogenic agents
journal, March 2006

  • Eldor, R.; Yeffet, A.; Baum, K.
  • Proceedings of the National Academy of Sciences, Vol. 103, Issue 13
  • DOI: 10.1073/pnas.0508166103

Proteomics Analysis of Cytokine-induced Dysfunction and Death in Insulin-producing INS-1E Cells: New Insights into the Pathways Involved
journal, October 2007

  • D'Hertog, Wannes; Overbergh, Lut; Lage, Kasper
  • Molecular & Cellular Proteomics, Vol. 6, Issue 12
  • DOI: 10.1074/mcp.M700085-MCP200

Viral infections in type 1 diabetes mellitus — why the β cells?
journal, March 2016

  • Op de Beeck, Anne; Eizirik, Decio L.
  • Nature Reviews Endocrinology, Vol. 12, Issue 5
  • DOI: 10.1038/nrendo.2016.30

Coxsackievirus-Induced Proteomic Alterations in Primary Human Islets Provide Insights for the Etiology of Diabetes
journal, September 2017

  • Nyalwidhe, Julius O.; Gallagher, Glen R.; Glenn, Lindsey M.
  • Journal of the Endocrine Society, Vol. 1, Issue 10
  • DOI: 10.1210/js.2017-00278

Differential cell autonomous responses determine the outcome of coxsackievirus infections in murine pancreatic α and β cells
journal, June 2015

  • Marroqui, Laura; Lopes, Miguel; dos Santos, Reinaldo S.
  • eLife, Vol. 4
  • DOI: 10.7554/eLife.06990

TiSH — a robust and sensitive global phosphoproteomics strategy employing a combination of TiO2, SIMAC, and HILIC
journal, October 2012

  • Engholm-Keller, Kasper; Birck, Pernille; Størling, Joachim
  • Journal of Proteomics, Vol. 75, Issue 18
  • DOI: 10.1016/j.jprot.2012.08.007

Quantitative Phosphoproteomics Revealed Glucose-Stimulated Responses of Islet Associated with Insulin Secretion
journal, October 2015


Glucose-regulated and drug-perturbed phosphoproteome reveals molecular mechanisms controlling insulin secretion
journal, November 2016

  • Sacco, Francesca; Humphrey, Sean J.; Cox, Jürgen
  • Nature Communications, Vol. 7, Issue 1
  • DOI: 10.1038/ncomms13250

Characterization of Membrane-shed Microvesicles from Cytokine-stimulated β-Cells Using Proteomics Strategies
journal, February 2012

  • Palmisano, Giuseppe; Jensen, Søren Skov; Le Bihan, Marie-Catherine
  • Molecular & Cellular Proteomics, Vol. 11, Issue 8
  • DOI: 10.1074/mcp.M111.012732

The Role for Endoplasmic Reticulum Stress in Diabetes Mellitus
journal, November 2007

  • Eizirik, Décio L.; Cardozo, Alessandra K.; Cnop, Miriam
  • Endocrine Reviews, Vol. 29, Issue 1
  • DOI: 10.1210/er.2007-0015

Signalling danger: endoplasmic reticulum stress and the unfolded protein response in pancreatic islet inflammation
journal, November 2012


ER Stress in Pancreatic   Cells: The Thin Red Line Between Adaptation and Failure
journal, February 2010


Novel Insights into the Global Proteome Responses of Insulin-Producing INS-1E Cells To Different Degrees of Endoplasmic Reticulum Stress
journal, October 2010

  • D’Hertog, Wannes; Maris, Michael; Ferreira, Gabriela B.
  • Journal of Proteome Research, Vol. 9, Issue 10
  • DOI: 10.1021/pr1004086

Early differences in islets from prediabetic NOD mice: combined microarray and proteomic analysis
journal, January 2017


GATA Factors Promote ER Integrity and β-Cell Survival and Contribute to Type 1 Diabetes Risk
journal, January 2014

  • Sartori, Daniel J.; Wilbur, Christopher J.; Long, Simon Y.
  • Molecular Endocrinology, Vol. 28, Issue 1
  • DOI: 10.1210/me.2013-1265

Islet  -Cell Endoplasmic Reticulum Stress Precedes the Onset of Type 1 Diabetes in the Nonobese Diabetic Mouse Model
journal, March 2012

  • Tersey, S. A.; Nishiki, Y.; Templin, A. T.
  • Diabetes, Vol. 61, Issue 4
  • DOI: 10.2337/db11-1293

Restoration of the Unfolded Protein Response in Pancreatic   Cells Protects Mice Against Type 1 Diabetes
journal, November 2013


Expression of endoplasmic reticulum stress markers in the islets of patients with type 1 diabetes
journal, June 2012


Characterization of hydroxyl radical modified GAD 65 : A potential autoantigen in type 1 diabetes
journal, January 2009


The insulin A-chain epitope recognized by human T cells is posttranslationally modified
journal, October 2005

  • Mannering, Stuart I.; Harrison, Leonard C.; Williamson, Nicholas A.
  • The Journal of Experimental Medicine, Vol. 202, Issue 9
  • DOI: 10.1084/jem.20051251

Recognition of Posttranslationally Modified GAD65 Epitopes in Subjects With Type 1 Diabetes
journal, April 2014

  • McGinty, J. W.; Chow, I. -T.; Greenbaum, C.
  • Diabetes, Vol. 63, Issue 9
  • DOI: 10.2337/db13-1952

Autoimmunity against a defective ribosomal insulin gene product in type 1 diabetes
journal, February 2017

  • Kracht, Maria J. L.; van Lummel, Menno; Nikolic, Tatjana
  • Nature Medicine, Vol. 23, Issue 4
  • DOI: 10.1038/nm.4289

Serum proteomics reveals systemic dysregulation of innate immunity in type 1 diabetes
journal, December 2012

  • Zhang, Qibin; Fillmore, Thomas L.; Schepmoes, Athena A.
  • The Journal of Experimental Medicine, Vol. 210, Issue 1
  • DOI: 10.1084/jem.20111843

Peptide serum markers in islet autoantibody-positive children
journal, November 2016

  • von Toerne, Christine; Laimighofer, Michael; Achenbach, Peter
  • Diabetologia, Vol. 60, Issue 2
  • DOI: 10.1007/s00125-016-4150-x

Serum Proteomes Distinguish Children Developing Type 1 Diabetes in a Cohort With HLA-Conferred Susceptibility
journal, January 2015

  • Moulder, Robert; Bhosale, Santosh D.; Erkkilä, Timo
  • Diabetes, Vol. 64, Issue 6
  • DOI: 10.2337/db14-0983

Quantitative Differences in the Urinary Proteome of Siblings Discordant for Type 1 Diabetes Include Lysosomal Enzymes
journal, June 2015


Type 1 Diabetes: Urinary Proteomics and Protein Network Analysis Support Perturbation of Lysosomal Function
journal, January 2017

  • Singh, Harinder; Yu, Yanbao; Suh, Moo-Jin
  • Theranostics, Vol. 7, Issue 10
  • DOI: 10.7150/thno.19679

Serum biomarkers for diagnosis and prediction of type 1 diabetes
journal, November 2018


High-Abundance Polypeptides of the Human Plasma Proteome Comprising the Top 4 Logs of Polypeptide Abundance
journal, August 2008


Quantitative variability of 342 plasma proteins in a human twin population
journal, February 2015

  • Liu, Yansheng; Buil, Alfonso; Collins, Ben C.
  • Molecular Systems Biology, Vol. 11, Issue 2
  • DOI: 10.15252/msb.20145728

Plasma Proteome Profiling to Assess Human Health and Disease
journal, March 2016


Temporal expression profiling of plasma proteins reveals oxidative stress in early stages of Type 1 Diabetes progression
journal, February 2018


Deep-Dive Targeted Quantification for Ultrasensitive Analysis of Proteins in Nondepleted Human Blood Plasma/Serum and Tissues
journal, August 2017


Progression to Diabetes in Relatives of Type 1 Diabetic Patients: Mechanisms and Mode of Onset
journal, December 2009

  • Ferrannini, E.; Mari, A.; Nofrate, V.
  • Diabetes, Vol. 59, Issue 3
  • DOI: 10.2337/db09-1378

Patterns of Metabolic Progression to Type 1 Diabetes in the Diabetes Prevention Trial-Type 1
journal, February 2006


β Cell dysfunction exists more than 5 years before type 1 diabetes diagnosis
journal, August 2018


Elevations in the Fasting Serum Proinsulin–to–C-Peptide Ratio Precede the Onset of Type 1 Diabetes
journal, July 2016

  • Sims, Emily K.; Chaudhry, Zunaira; Watkins, Renecia
  • Diabetes Care, Vol. 39, Issue 9
  • DOI: 10.2337/dc15-2849

Measurement of Pro-Islet Amyloid Polypeptide (1–48) in Diabetes and Islet Transplants
journal, March 2017

  • Courtade, Jaques A.; Klimek-Abercrombie, Agnieszka M.; Chen, Yi-Chun
  • The Journal of Clinical Endocrinology & Metabolism, Vol. 102, Issue 7
  • DOI: 10.1210/jc.2016-2773

Circulating microRNAs as novel biomarkers for diabetes mellitus
journal, April 2013


MicroRNA 21 targets BCL2 mRNA to increase apoptosis in rat and human beta cells
journal, March 2017

  • Sims, Emily K.; Lakhter, Alexander J.; Anderson-Baucum, Emily
  • Diabetologia, Vol. 60, Issue 6
  • DOI: 10.1007/s00125-017-4237-z

MicroRNAs miR-23a-3p, miR-23b-3p, and miR-149-5p Regulate the Expression of Proapoptotic BH3-Only Proteins DP5 and PUMA in Human Pancreatic β-Cells
journal, October 2016

  • Grieco, Fabio Arturo; Sebastiani, Guido; Juan-Mateu, Jonas
  • Diabetes, Vol. 66, Issue 1
  • DOI: 10.2337/db16-0592

The MicroRNA Spectrum in 12 Body Fluids
journal, September 2010


Profiling of circulating microRNAs in children with recent onset of type 1 diabetes
journal, February 2017


Lymphocyte-Derived Exosomal MicroRNAs Promote Pancreatic β Cell Death and May Contribute to Type 1 Diabetes Development
journal, February 2019


Beta cell extracellular vesicle miR-21-5p cargo is increased in response to inflammatory cytokines and serves as a biomarker of type 1 diabetes
journal, February 2018


Plasma-derived exosome characterization reveals a distinct microRNA signature in long duration Type 1 diabetes
journal, July 2017


Glypican-1 identifies cancer exosomes and detects early pancreatic cancer
journal, June 2015

  • Melo, Sonia A.; Luecke, Linda B.; Kahlert, Christoph
  • Nature, Vol. 523, Issue 7559
  • DOI: 10.1038/nature14581

Tissue-specific exosome biomarkers for noninvasively monitoring immunologic rejection of transplanted tissue
journal, March 2017

  • Vallabhajosyula, Prashanth; Korutla, Laxminarayana; Habertheuer, Andreas
  • Journal of Clinical Investigation, Vol. 127, Issue 4
  • DOI: 10.1172/JCI87993

Chip-based analysis of exosomal mRNA mediating drug resistance in glioblastoma
journal, May 2015

  • Shao, Huilin; Chung, Jaehoon; Lee, Kyungheon
  • Nature Communications, Vol. 6, Issue 1
  • DOI: 10.1038/ncomms7999

Acoustic Purification of Extracellular Microvesicles
journal, February 2015

  • Lee, Kyungheon; Shao, Huilin; Weissleder, Ralph
  • ACS Nano, Vol. 9, Issue 3
  • DOI: 10.1021/nn506538f

Detection of   cell death in diabetes using differentially methylated circulating DNA
journal, November 2011

  • Akirav, E. M.; Lebastchi, J.; Galvan, E. M.
  • Proceedings of the National Academy of Sciences, Vol. 108, Issue 47
  • DOI: 10.1073/pnas.1111008108

Detection of Islet β-Cell Death in Vivo by Multiplex PCR Analysis of Differentially Methylated DNA
journal, September 2013

  • Fisher, Marisa M.; Perez Chumbiauca, Cristina N.; Mather, Kieren J.
  • Endocrinology, Vol. 154, Issue 9
  • DOI: 10.1210/en.2013-1223

Identification of tissue-specific cell death using methylation patterns of circulating DNA
journal, March 2016

  • Lehmann-Werman, Roni; Neiman, Daniel; Zemmour, Hai
  • Proceedings of the National Academy of Sciences, Vol. 113, Issue 13
  • DOI: 10.1073/pnas.1519286113

β Cell death and dysfunction during type 1 diabetes development in at-risk individuals
journal, February 2015

  • Herold, Kevan C.; Usmani-Brown, Sahar; Ghazi, Tara
  • Journal of Clinical Investigation, Vol. 125, Issue 3
  • DOI: 10.1172/JCI78142

Circulating Differentially Methylated Amylin DNA as a Biomarker of β-Cell Loss in Type 1 Diabetes
journal, April 2016


Glucokinase Gene May Be a More Suitable Target Than the Insulin Gene for Detection of β Cell Death
journal, May 2017

  • Sklenarova, Jana; Petruzelkova, Lenka; Kolouskova, Stanislava
  • Endocrinology, Vol. 158, Issue 7
  • DOI: 10.1210/en.2016-1923

Quantitative proteomic analysis of single pancreatic islets
journal, October 2009

  • Waanders, Leonie F.; Chwalek, Karolina; Monetti, Mara
  • Proceedings of the National Academy of Sciences, Vol. 106, Issue 45
  • DOI: 10.1073/pnas.0908351106

Proteomic profiling of human islets collected from frozen pancreata using laser capture microdissection
journal, January 2017


Spatially-Resolved Proteomics: Rapid Quantitative Analysis of Laser Capture Microdissected Alveolar Tissue Samples
journal, December 2016

  • Clair, Geremy; Piehowski, Paul D.; Nicola, Teodora
  • Scientific Reports, Vol. 6, Issue 1
  • DOI: 10.1038/srep39223

Development and Evaluation of a Micro- and Nanoscale Proteomic Sample Preparation Method
journal, December 2005

  • Wang, Haixing; Qian, Wei-Jun; Mottaz, Heather M.
  • Journal of Proteome Research, Vol. 4, Issue 6
  • DOI: 10.1021/pr050160f

An Integrated Platform for Isolation, Processing, and Mass Spectrometry-based Proteomic Profiling of Rare Cells in Whole Blood
journal, March 2015

  • Li, Siyang; Plouffe, Brian D.; Belov, Arseniy M.
  • Molecular & Cellular Proteomics, Vol. 14, Issue 6
  • DOI: 10.1074/mcp.M114.045724

Ultrasensitive Proteome Profiling for 100 Living Cells by Direct Cell Injection, Online Digestion and Nano-LC-MS/MS Analysis
journal, June 2015


Nanoliter-Scale Oil-Air-Droplet Chip-Based Single Cell Proteomic Analysis
journal, March 2018


SCoPE-MS: mass spectrometry of single mammalian cells quantifies proteome heterogeneity during cell differentiation
journal, October 2018


Nanodroplet processing platform for deep and quantitative proteome profiling of 10–100 mammalian cells
journal, February 2018


Heterogeneity of the Human Pancreatic Islet
journal, April 2019


Nanowell-mediated two-dimensional liquid chromatography enables deep proteome profiling of <1000 mammalian cells
journal, January 2018

  • Dou, Maowei; Zhu, Ying; Liyu, Andrey
  • Chemical Science, Vol. 9, Issue 34
  • DOI: 10.1039/C8SC02680G

Integrating ion mobility spectrometry into mass spectrometry-based exposome measurements: what can it add and how far can it go?
journal, January 2017

  • Metz, Thomas O.; Baker, Erin S.; Schymanski, Emma L.
  • Bioanalysis, Vol. 9, Issue 1
  • DOI: 10.4155/bio-2016-0244

SPE-IMS-MS: An automated platform for sub-sixty second surveillance of endogenous metabolites and xenobiotics in biofluids
journal, December 2016


Online Parallel Accumulation–Serial Fragmentation (PASEF) with a Novel Trapped Ion Mobility Mass Spectrometer
journal, November 2018

  • Meier, Florian; Brunner, Andreas-David; Koch, Scarlet
  • Molecular & Cellular Proteomics, Vol. 17, Issue 12
  • DOI: 10.1074/mcp.TIR118.000900

Experimental Evaluation and Optimization of Structures for Lossless Ion Manipulations for Ion Mobility Spectrometry with Time-of-Flight Mass Spectrometry
journal, September 2014

  • Webb, Ian K.; Garimella, Sandilya V. B.; Tolmachev, Aleksey V.
  • Analytical Chemistry, Vol. 86, Issue 18, p. 9169-9176
  • DOI: 10.1021/ac502055e

Nanowell-mediated multidimensional separations combining nanoLC with SLIM IM-MS for rapid, high-peak-capacity proteomic analyses
journal, November 2018

  • Dou, Maowei; Chouinard, Christopher D.; Zhu, Ying
  • Analytical and Bioanalytical Chemistry, Vol. 411, Issue 21
  • DOI: 10.1007/s00216-018-1452-5

Single-Cell Mass Cytometry of Differential Immune and Drug Responses Across a Human Hematopoietic Continuum
journal, May 2011


Multiplexed Epitope-Based Tissue Imaging for Discovery and Healthcare Applications
journal, April 2016


Single-Cell Mass Cytometry Analysis of the Human Endocrine Pancreas
journal, October 2016


The long lifespan and low turnover of human islet beta cells estimated by mathematical modelling of lipofuscin accumulation
journal, October 2009


Mass Cytometry Identifies Distinct Subsets of Regulatory T Cells and Natural Killer Cells Associated With High Risk for Type 1 Diabetes
journal, May 2019


Multiplexed In Situ Imaging Mass Cytometry Analysis of the Human Endocrine Pancreas and Immune System in Type 1 Diabetes
journal, March 2019


A Map of Human Type 1 Diabetes Progression by Imaging Mass Cytometry
journal, March 2019