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Mark Chance, PhD

Mark Chance, PhD

Professor 216.368.1490 (o)

Dr. Chance is an internationally recognized expert in proteomics and structural biology with over 270 publications who has built multiple internationally recognized science and training programs over a 25-year career in academia. He is also the Director of the Center for Proteomics and Bioinformatics (CPB) at Case Western Reserve University (CWRU). The faculty, staff and users of the CPB, including its structural biology facilities at Brookhaven National Laboratories, currently publish 100 papers per year using technologies ranging from next generation sequencing to mass spectrometry to crystallography and in fields from cancer to infectious disease to vision research. The CPB’s programs have attracted over $150 million in funding since 2005. He has been a leader in clinical and translational research within the Center for Translational Science Collaborative and the Case Comprehensive Cancer Center. He has led an NIH-funded Molecular Biophysics PhD program and recently established a Systems Biology and Bioinformatics graduate program at CWRU in 2011.

Recently, as Vice Dean for Research at the School of Medicine, he has reshaped the strategic directions of the Academic Medical Center in research and graduate education to respond to current trends in biomedical research. He has led an innovation and commercialization program to develop therapeutics, the Council for Advancing Human Health. He is a member of numerous advisory boards and frequently invited lecturer at national and international meetings. He has multiple patents and patent filings and has launched a successful startup company in the field of precision medicine, NeoProteomics, Inc. His career goals are to provide leadership as both a scientist and administrator to accelerate the development and translation of biomarkers and treatments for complex diseases and develop the next generation of scientific leaders through a wide range of academic and commercial initiatives.


Mark Chance CV (PDF)

Mark Chance Biosketch (PDF)

2015-Present Professor, Department of Nutrition, Case Western Reserve University, School of Medicine, Case Western Reserve University, Cleveland, OH
2011-Present Vice Dean for Research and Graduate Education, School of Medicine
2011-Present Charles W. and Iona A. Mathias Professor of Cancer Research
2010-Present Professor, Department of General Medical Sciences,
2010-Present Professor, Department of Genetics and Genome Sciences
2010-2012 Interim Chair, Department of Genetics and Genome Sciences
2009-Present Chief Scientific Officer, NeoProteomics, Inc. Cleveland, OH
2005-Present Director, Center for Proteomics and Bioinformatics
2005-2010 Professor, Department of Physiology & Biophysics
1995-Present Director, Center for Synchrotron Biosciences, National Synchrotron Light Source, Brookhaven Labs

2014 Naomi Kanof Investigator Award Lectureship and Medal for Distinguished Achievement in Clinical Investigation, Awarded by the Society of Investigative Dermatology
2015-Present National Prion Disease Pathology Surveillance Center Advisory Committee
2014-2015 Member, NIGMS National Centers for Systems Biology Program Evaluation Committee
2014, 2013 Member, NIGMS Systems Biology Center Review Panel (also 2007)
2014 Member, NIAMS Accelerating Medicines Partnership in Rheumatoid Arthritis and Lupus Review Panel
2010-2020 Editorial Board Member, Molecular and Cellular Proteomics
2010-2015 Editorial Board Member, Journal of Clinical Bioinformatics

1986 Ph.D. (Biophysics), University of Pennsylvania
1980-1984 Graduate courses and qualifying examination in Biochemistry, Massachusetts Institute of Technology
1980 B.A. with Honors in Biology, (cum laude) Wesleyan University

Publications for the past 5 years:


Hulscher RM, Bohon J, Rappé MC, Gupta S, D'Mello R, Sullivan M, Ralston CY,

Chance MR, Woodson SA. Probing the structure of ribosome assembly intermediates

in vivo using DMS and hydroxyl radical footprinting. Methods. 2016 Jul

1;103:49-56. doi: 10.1016/j.ymeth.2016.03.012. Epub 2016 Mar 22. PubMed

[citation] PMID: 27016143, PMCID: PMC4921310


Shukla S, Kanwal R, Shankar E, Datt M, Chance MR, Fu P, MacLennan GT, Gupta S.

Apigenin blocks IKKα activation and suppresses prostate cancer progression.

Oncotarget. 2015 Oct 13;6(31):31216-32. doi: 10.18632/oncotarget.5157. PubMed

[citation] PMID: 26435478, PMCID: PMC4741599


Tomechko SE, Lundberg KC, Jarvela J, Bebek G, Chesnokov NG, Schlatzer D, Ewing

RM, Boom WH, Chance MR, Silver RF. Proteomic and bioinformatics profile of paired

human alveolar macrophages and peripheral blood monocytes. Proteomics. 2015

Nov;15(22):3797-805. doi: 10.1002/pmic.201400496. PubMed [citation] PMID:



Kaur P, Tomechko SE, Kiselar J, Shi W, Deperalta G, Wecksler AT, Gokulrangan G,

Ling V, Chance MR. Characterizing monoclonal antibody structure by carboxyl group

footprinting. MAbs. 2015;7(3):540-52. doi: 10.1080/19420862.2015.1023683. PubMed

[citation] PMID: 25933350, PMCID: PMC4622658


Mbonye UR, Wang B, Gokulrangan G, Chance MR, Karn J. Phosphorylation of HEXIM1 at

Tyr271 and Tyr274 Promotes Release of P-TEFb from the 7SK snRNP Complex and

Enhances Proviral HIV Gene Expression. Proteomics. 2015 Jun;15(12):2078-86. doi:

10.1002/pmic.201500038. Epub 2015 May 15. PubMed [citation] PMID: 25900325,

PMCID: PMC4487608


Wang L, Chance MR. Detection of structural waters and their role in structural

dynamics of rhodopsin activation. Methods Mol Biol. 2015;1271:97-111. doi:

10.1007/978-1-4939-2330-4_7. PubMed [citation] PMID: 25697519


Kaur P, Kiselar J, Yang S, Chance MR. Quantitative protein topography analysis

and high-resolution structure prediction using hydroxyl radical labeling and

tandem-ion mass spectrometry (MS). Mol Cell Proteomics. 2015 Apr;14(4):1159-68.

doi: 10.1074/mcp.O114.044362. Epub 2015 Feb 16. PubMed [citation] PMID: 25687570,

PMCID: PMC4390260


Kerner J, Yohannes E, Lee K, Virmani A, Koverech A, Cavazza C, Chance MR, Hoppel

C. Acetyl-L-carnitine increases mitochondrial protein acetylation in the aged rat

heart. Mech Ageing Dev. 2015 Jan;145:39-50. doi: 10.1016/j.mad.2015.01.003. Epub

2015 Feb 7. PubMed [citation] PMID: 25660059, PMCID: PMC4712450


Tomechko SE, Liu G, Tao M, Schlatzer D, Powell CT, Gupta S, Chance MR, Daneshgari

F. Tissue specific dysregulated protein subnetworks in type 2 diabetic bladder

urothelium and detrusor muscle. Mol Cell Proteomics. 2015 Mar;14(3):635-45. doi:

10.1074/mcp.M114.041863. Epub 2015 Jan 8. PubMed [citation] PMID: 25573746,

PMCID: PMC4349983


Huang W, Ravikumar KM, Chance MR, Yang S. Quantitative mapping of protein

structure by hydroxyl radical footprinting-mediated structural mass spectrometry:

a protection factor analysis. Biophys J. 2015 Jan 6;108(1):107-15. doi:

10.1016/j.bpj.2014.11.013. Erratum in: Biophys J. 2015 Feb 3;108(3):780. PubMed

[citation] PMID: 25564857, PMCID: PMC4286602


Kaur P, Tomechko S, Kiselar J, Shi W, Deperalta G, Wecksler AT, Gokulrangan G,

Ling V, Chance MR. Characterizing monoclonal antibody structure by

carbodiimide/GEE footprinting. MAbs. 2014;6(6):1486-99. doi:

10.4161/19420862.2014.975096. Retraction in: MAbs. 2015;7(3):651. PubMed

[citation] PMID: 25484052, PMCID: PMC4622050


Klinger AL, Kiselar J, Ilchenko S, Komatsu H, Chance MR, Axelsen PH. A

synchrotron-based hydroxyl radical footprinting analysis of amyloid fibrils and

prefibrillar intermediates with residue-specific resolution. Biochemistry. 2014

Dec 16;53(49):7724-34. doi: 10.1021/bi5010409. Epub 2014 Dec 3. PubMed [citation]

PMID: 25382225, PMCID: PMC4270378


Lundberg KC, Fritz Y, Johnston A, Foster AM, Baliwag J, Gudjonsson JE, Schlatzer

D, Gokulrangan G, McCormick TS, Chance MR, Ward NL. Proteomics of skin proteins

in psoriasis: from discovery and verification in a mouse model to confirmation in

humans. Mol Cell Proteomics. 2015 Jan;14(1):109-19. doi: 10.1074/mcp.M114.042242.

Epub 2014 Oct 28. PubMed [citation] PMID: 25351201, PMCID: PMC4288247


Liu Y, Chance MR. Integrating phosphoproteomics in systems biology. Comput Struct

Biotechnol J. 2014 Jul;10(17):90-7. doi: 10.1016/j.csbj.2014.07.003. Review.

PubMed [citation] PMID: 25349677, PMCID: PMC4204398


Guyuron B, Yohannes E, Miller R, Chim H, Reed D, Chance MR. Electron microscopic

and proteomic comparison of terminal branches of the trigeminal nerve in patients

with and without migraine headaches. Plast Reconstr Surg. 2014

Nov;134(5):796e-805e. doi: 10.1097/PRS.0000000000000696. PubMed [citation] PMID:

25347655, PMCID: PMC4465394


Manjasetty BA, Chance MR, Burley SK, Panjikar S, Almo SC. Crystal structure of

Clostridium acetobutylicum Aspartate kinase (CaAK): An important allosteric

enzyme for amino acids production. Biotechnol Rep (Amst). 2014 Sep 1;3:73-85.

PubMed [citation] PMID: 25170437, PMCID: PMC4142519


Liu Y, Koyutürk M, Maxwell S, Xiang M, Veigl M, Cooper RS, Tayo BO, Li L,

LaFramboise T, Wang Z, Zhu X, Chance MR. Discovery of common sequences absent in

the human reference genome using pooled samples from next generation sequencing.

BMC Genomics. 2014 Aug 16;15:685. doi: 10.1186/1471-2164-15-685. PubMed

[citation] PMID: 25129063, PMCID: PMC4148959


Gupta S, Chai J, Cheng J, D'Mello R, Chance MR, Fu D. Visualizing the kinetic

power stroke that drives proton-coupled zinc(II) transport. Nature. 2014 Aug

7;512(7512):101-4. doi: 10.1038/nature13382. Epub 2014 Jun 22. PubMed [citation]

PMID: 25043033, PMCID: PMC4144069


Gupta S, Celestre R, Petzold CJ, Chance MR, Ralston C. Development of a

microsecond X-ray protein footprinting facility at the Advanced Light Source. J

Synchrotron Radiat. 2014 Jul;21(Pt 4):690-9. doi: 10.1107/S1600577514007000. Epub

2014 May 16. PubMed [citation] PMID: 24971962, PMCID: PMC4073957


Salanga CL, Dyer DP, Kiselar JG, Gupta S, Chance MR, Handel TM. Multiple

glycosaminoglycan-binding epitopes of monocyte chemoattractant protein-3/CCL7

enable it to function as a non-oligomerizing chemokine. J Biol Chem. 2014 May

23;289(21):14896-912. doi: 10.1074/jbc.M114.547737. Epub 2014 Apr 11. PubMed

[citation] PMID: 24727473, PMCID: PMC4031540


Wang B, Tsybovsky Y, Palczewski K, Chance MR. Reliable determination of

site-specific in vivo protein N-glycosylation based on collision-induced MS/MS

and chromatographic retention time. J Am Soc Mass Spectrom. 2014

May;25(5):729-41. doi: 10.1007/s13361-013-0823-6. Epub 2014 Feb 19. PubMed

[citation] PMID: 24549892, PMCID: PMC3988243


Bohon J, D'Mello R, Ralston C, Gupta S, Chance MR. Synchrotron X-ray footprinting

on tour. J Synchrotron Radiat. 2014 Jan;21(Pt 1):24-31. doi:

10.1107/S1600577513024715. Epub 2013 Nov 2. PubMed [citation] PMID: 24365913,

PMCID: PMC3874017


Liu Y, Chance MR. Pathway analyses and understanding disease associations. Curr

Genet Med Rep. 2013 Dec 1;1(4). doi: 10.1007/s40142-013-0025-3. PubMed [citation]

PMID: 24319650, PMCID: PMC3851310


Di XJ, Han DY, Wang YJ, Chance MR, Mu TW. SAHA enhances Proteostasis of

epilepsy-associated α1(A322D)β2γ2 GABA(A) receptors. Chem Biol. 2013 Dec

19;20(12):1456-68. doi: 10.1016/j.chembiol.2013.09.020. Epub 2013 Nov 7. PubMed

[citation] PMID: 24211135, PMCID: PMC3872227


Patel VN, Gokulrangan G, Chowdhury SA, Chen Y, Sloan AE, Koyutürk M,

Barnholtz-Sloan J, Chance MR. Network signatures of survival in glioblastoma

multiforme. PLoS Comput Biol. 2013;9(9):e1003237. doi:

10.1371/journal.pcbi.1003237. Epub 2013 Sep 19. PubMed [citation] PMID: 24068912,

PMCID: PMC3777929


Ghosh SK, McCormick TS, Eapen BL, Yohannes E, Chance MR, Weinberg A. Comparison

of epigenetic profiles of human oral epithelial cells from HIV-positive (on

HAART) and HIV-negative subjects. Epigenetics. 2013 Jul;8(7):703-9. doi:

10.4161/epi.25028. Epub 2013 May 17. PubMed [citation] PMID: 23804146, PMCID:



Meisch JP, Vogel RM, Schlatzer DM, Li X, Chance MR, Levine AD. Human β-defensin 3

induces STAT1 phosphorylation, tyrosine phosphatase activity, and cytokine

synthesis in T cells. J Leukoc Biol. 2013 Sep;94(3):459-71. doi:

10.1189/jlb.0612300. Epub 2013 Jun 26. PubMed [citation] PMID: 23804808, PMCID:



Bjelić S, Wieser M, Frey D, Stirnimann CU, Chance MR, Jaussi R, Steinmetz MO,

Kammerer RA. Structural basis for the oligomerization-state switch from a dimer

to a trimer of an engineered cortexillin-1 coiled-coil variant. PLoS One. 2013

May 14;8(5):e63370. doi: 10.1371/journal.pone.0063370. Print 2013. PubMed

[citation] PMID: 23691037, PMCID: PMC3653964


Mbonye UR, Gokulrangan G, Datt M, Dobrowolski C, Cooper M, Chance MR, Karn J.

Phosphorylation of CDK9 at Ser175 enhances HIV transcription and is a marker of

activated P-TEFb in CD4(+) T lymphocytes. PLoS Pathog. 2013;9(5):e1003338. doi:

10.1371/journal.ppat.1003338. Epub 2013 May 2. PubMed [citation] PMID: 23658523,

PMCID: PMC3642088


Schlatzer DM, Sugalski JM, Chen Y, Barnholtz-Sloan J, Davitkov P, Hazlett FE,

Funderburg N, Rodriguez B, Lederman MM, Sieg SF, Chance MR, Anthony DD. Plasma

proteome analysis reveals overlapping, yet distinct mechanisms of immune

activation in chronic HCV and HIV infections. J Acquir Immune Defic Syndr. 2013

Aug 15;63(5):563-71. doi: 10.1097/QAI.0b013e3182909847. PubMed [citation] PMID:

23507661, PMCID: PMC3762939


Padayatti PS, Wang L, Gupta S, Orban T, Sun W, Salom D, Jordan SR, Palczewski K,

Chance MR. A hybrid structural approach to analyze ligand binding by the

serotonin type 4 receptor (5-HT4). Mol Cell Proteomics. 2013 May;12(5):1259-71.

doi: 10.1074/mcp.M112.025536. Epub 2013 Feb 1. PubMed [citation] PMID: 23378516,

PMCID: PMC3650337


Liu Y, Maxwell S, Feng T, Zhu X, Elston RC, Koyutürk M, Chance MR. Gene, pathway

and network frameworks to identify epistatic interactions of single nucleotide

polymorphisms derived from GWAS data. BMC Syst Biol. 2012;6 Suppl 3:S15. doi:

10.1186/1752-0509-6-S3-S15. Epub 2012 Dec 17. PubMed [citation] PMID: 23281810,

PMCID: PMC3524014


Erten S, Chowdhury SA, Guan X, Nibbe RK, Barnholtz-Sloan JS, Chance MR, Koyutürk

M. Identifying stage-specific protein subnetworks for colorectal cancer. BMC

Proc. 2012 Nov 13;6 Suppl 7:S1. doi: 10.1186/1753-6561-6-S7-S1. Epub 2012 Nov 13.

PubMed [citation] PMID: 23173715, PMCID: PMC3504924


Ghosh SK, Yohannes E, Bebek G, Weinberg A, Jiang B, Willard B, Chance MR, Kinter

MT, McCormick TS. Proteomic and bioinformatic profile of primary human oral

epithelial cells. J Proteome Res. 2012 Nov 2;11(11):5492-502. doi:

10.1021/pr3007254. Epub 2012 Oct 16. PubMed [citation] PMID: 23035736, PMCID:



Kiser PD, Farquhar ER, Shi W, Sui X, Chance MR, Palczewski K. Structure of RPE65

isomerase in a lipidic matrix reveals roles for phospholipids and iron in

catalysis. Proc Natl Acad Sci U S A. 2012 Oct 9;109(41):E2747-56. doi:

10.1073/pnas.1212025109. Epub 2012 Sep 24. PubMed [citation] PMID: 23012475,

PMCID: PMC3478654


Gupta S, D'Mello R, Chance MR. Structure and dynamics of protein waters revealed

by radiolysis and mass spectrometry. Proc Natl Acad Sci U S A. 2012 Sep

11;109(37):14882-7. doi: 10.1073/pnas.1209060109. Epub 2012 Aug 27. PubMed

[citation] PMID: 22927377, PMCID: PMC3443160


Kaur P, Schlatzer D, Cooke K, Chance MR. Pairwise protein expression classifier

for candidate biomarker discovery for early detection of human disease prognosis.

BMC Bioinformatics. 2012 Aug 7;13:191. doi: 10.1186/1471-2105-13-191. PubMed

[citation] PMID: 22870920, PMCID: PMC3468399


Liu Y, Koyutürk M, Maxwell S, Zhao Z, Chance MR. Integrative analysis of common

neurodegenerative diseases using gene association, interaction networks and mRNA

expression data. AMIA Jt Summits Transl Sci Proc. 2012;2012:62-71. Epub 2012 Mar

19. PubMed [citation] PMID: 22779053, PMCID: PMC3392058


Liu Y, Koyutürk M, Barnholtz-Sloan JS, Chance MR. Gene interaction enrichment and

network analysis to identify dysregulated pathways and their interactions in

complex diseases. BMC Syst Biol. 2012 Jun 13;6:65. doi: 10.1186/1752-0509-6-65.

PubMed [citation] PMID: 22694839, PMCID: PMC3426489


Linderman GC, Chance MR, Bebek G. MAGNET: MicroArray Gene expression and Network

Evaluation Toolkit. Nucleic Acids Res. 2012 Jul;40(Web Server issue):W152-6. doi:

10.1093/nar/gks526. Epub 2012 Jun 4. PubMed [citation] PMID: 22669910, PMCID:



Guan X, Chance MR, Barnholtz-Sloan JS. Splitting random forest (SRF) for

determining compact sets of genes that distinguish between cancer subtypes. J

Clin Bioinforma. 2012 May 22;2(1):13. doi: 10.1186/2043-9113-2-13. PubMed

[citation] PMID: 22616791, PMCID: PMC3444418


Manjasetty BA, Yu XH, Panjikar S, Taguchi G, Chance MR, Liu CJ. Structural basis

for modification of flavonol and naphthol glucoconjugates by Nicotiana tabacum

malonyltransferase (NtMaT1). Planta. 2012 Sep;236(3):781-93. doi:

10.1007/s00425-012-1660-8. Epub 2012 May 19. PubMed [citation] PMID: 22610270


Orban T, Jastrzebska B, Gupta S, Wang B, Miyagi M, Chance MR, Palczewski K.

Conformational dynamics of activation for the pentameric complex of dimeric G

protein-coupled receptor and heterotrimeric G protein. Structure. 2012 May

9;20(5):826-40. doi: 10.1016/j.str.2012.03.017. PubMed [citation] PMID: 22579250,

PMCID: PMC3351692


Bebek G, Koyutürk M, Price ND, Chance MR. Network biology methods integrating

biological data for translational science. Brief Bioinform. 2012

Jul;13(4):446-59. doi: 10.1093/bib/bbr075. Epub 2012 Mar 5. Review. PubMed

[citation] PMID: 22390873, PMCID: PMC3404396


Chen Y, Farquhar ER, Chance MR, Palczewski K, Kiser PD. Insights into substrate

specificity and metal activation of mammalian tetrahedral aspartyl

aminopeptidase. J Biol Chem. 2012 Apr 13;287(16):13356-70. doi:

10.1074/jbc.M112.347518. Epub 2012 Feb 22. PubMed [citation] PMID: 22356908,

PMCID: PMC3339940


Schlatzer DM, Dazard JE, Ewing RM, Ilchenko S, Tomcheko SE, Eid S, Ho V, Yanik G,

Chance MR, Cooke KR. Human biomarker discovery and predictive models for disease

progression for idiopathic pneumonia syndrome following allogeneic stem cell

transplantation. Mol Cell Proteomics. 2012 Jun;11(6):M111.015479. doi:

10.1074/mcp.M111.015479. Epub 2012 Feb 15. PubMed [citation] PMID: 22337588,

PMCID: PMC3433920


Schlatzer D, Maahs DM, Chance MR, Dazard JE, Li X, Hazlett F, Rewers M,

Snell-Bergeon JK. Novel urinary protein biomarkers predicting the development of

microalbuminuria and renal function decline in type 1 diabetes. Diabetes Care.

2012 Mar;35(3):549-55. doi: 10.2337/dc11-1491. Epub 2012 Jan 11. PubMed

[citation] PMID: 22238279, PMCID: PMC3322681


Wang L, Cvetkov TL, Chance MR, Moiseenkova-Bell VY. Identification of in vivo

disulfide conformation of TRPA1 ion channel. J Biol Chem. 2012 Feb

24;287(9):6169-76. doi: 10.1074/jbc.M111.329748. Epub 2011 Dec 29. PubMed

[citation] PMID: 22207754, PMCID: PMC3307328


Yohannes E, Ghosh SK, Jiang B, McCormick TS, Weinberg A, Hill E, Faddoul F,

Chance MR. Proteomic signatures of human oral epithelial cells in HIV-infected

subjects. PLoS One. 2011;6(11):e27816. doi: 10.1371/journal.pone.0027816. Epub

2011 Nov 16. PubMed [citation] PMID: 22114700, PMCID: PMC3218055


Kiselar JG, Datt M, Chance MR, Weiss MA. Structural analysis of proinsulin

hexamer assembly by hydroxyl radical footprinting and computational modeling. J

Biol Chem. 2011 Dec 23;286(51):43710-6. doi: 10.1074/jbc.M111.297853. Epub 2011

Oct 26. PubMed [citation] PMID: 22033917, PMCID: PMC3243561


Oztug Durer ZA, Kamal JK, Benchaar S, Chance MR, Reisler E. Myosin binding

surface on actin probed by hydroxyl radical footprinting and site-directed

labels. J Mol Biol. 2011 Nov 25;414(2):204-16. doi: 10.1016/j.jmb.2011.09.035.

Epub 2011 Oct 1. PubMed [citation] PMID: 21986200, PMCID: PMC3221818






Schlatzer DM, Sugalski J, Dazard JE, Chance MR, Anthony DD. A quantitative

proteomic approach for detecting protein profiles of activated human myeloid

dendritic cells. J Immunol Methods. 2012 Jan 31;375(1-2):39-45. doi:

10.1016/j.jim.2011.09.004. Epub 2011 Sep 16. PubMed [citation] PMID: 21945394,

PMCID: PMC3253886


Berman LE, Allaire M, Chance MR, Hendrickson WA, Héroux A, Jakoncic J, Liu Q,

Orville AM, Robinson HH, Schneider DK, Shi W, Soares AS, Stojanoff V, Stoner-Ma

D, Sweet RM. Optics Concept for a Pair of Undulator Beamlines for MX. Nucl

Instrum Methods Phys Res A. 2011 Sep 1;649(1):131-135. PubMed [citation] PMID:

21822346, PMCID: PMC3150574


Wang L, Chance MR. Structural mass spectrometry of proteins using hydroxyl

radical based protein footprinting. Anal Chem. 2011 Oct 1;83(19):7234-41. doi:

10.1021/ac200567u. Epub 2011 Aug 1. PubMed [citation] PMID: 21770468, PMCID: