Norman PAVELKA

Principal Investigator

Adj. Assistant Prof (NTU), Visiting Scientist, Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands


  • Fabien COTTIER, Ph.D
  • Gloria TSO, Ph.D
  • Jose REALES, Ph.D
  • TAN Tze Guan, Ph.D
  • LAI Ghee Chuan, Ph.D
  • Alrina TAN
  • Flora TEOH Ph.D student

Profile

Research Focus

Candida albicans is the most common fungal colonizer and pathogen of humans.  It primarily inhabits the gastrointestinal (GI) tract, where it homeostatically interacts with the host immune system and the GI microbiota.  However, immune suppression or antibiotic treatment are known to disrupt this equilibrium and to lead to infections associated with high morbidity and mortality. The Pavelka lab is focused on understanding the ecological and evolutionary forces that govern the three-way interaction between C. albicans, GI bacteria and the immune system.  We are primarily studying the evolution of C. albicans under the selective pressures of the mammalian GI tract and the role played by the fungal cell wall in determining host-microbe interactions.  Moreover, we discovered microbiota-derived metabolites that inhibit C. albicans growth and fungal resistance mechanisms against these metabolites that could potentially be further altered by diet.  Finally, we are developing novel microbiome analysis methods to study GI bacteria and fungi in both healthy and diseased individuals and studying how changes in these communities affect immune responses.

Biography

Dr Pavelka received his Degree in Biotechnology from the University of Milano-Bicocca in 2001 and his Ph.D. in Immunology from the University of Rome “Tor Vergata” in 2006. He formerly worked as a graduate student in Prof Paola Castagnoli’s lab at the University of Milano-Bicocca, where he developed his microarray data analysis skills and contributed to numerous Functional Genomics projects aimed at understanding the role of dendritic cells in host-pathogen interactions. Dr Pavelka then joined Prof Rong Li’s group at the Stowers Institute for Medical Research as a Postdoctoral Research Associate in May 2006, where he published seminal papers on the role of aneuploidy in evolution of yeast cells. While at the Stowers Institute, he collaborated with Dr Michael Washburn, publishing important contributions to the proteomics data analysis field. In October 2010, Dr Pavelka was awarded the A*STAR Investigatorship in Biomedical Sciences and set up his laboratory at the Singapore Immunology Network in May 2011, to study the ecology and evolution of host-microbe interactions and the genome changes that underlie such complex and dynamic processes. Since 2011, Dr Pavelka is serving as an Associate Editor at Frontiers in Genetics (Section of Bioinformatics and Computational Biology) and in 2013 became Adjunct Assistant Professor at the School of Biological Sciences of the Nanyang Technological University of Singapore.

Projects

  • Immune factors shaping evolution of host-fungal interaction

    Candida albicans is a clinically important fungal pathogen for which drug resistances arise very frequently and for which a vaccine is not yet commercially available. It is characterized by remarkable genome plasticity that we hypothesize could facilitate rapid evolution of immune evasion and virulence mechanisms.

    read more
  • Interaction of fungal pathogens with the gut microbiome

    While Candida albicans is widely represented in the human population with an impact on health ranging from inoffensive to life threatening, this organism is generally absent from the gastrointestinal tract of mice.

    read more

Publications

2017

Schönherr FA, Sparber F, Kirchner FR, Guiducci E, Trautwein-Weidner K, Gladiator A, Sertour N, Hetzel U, Le GT, Pavelka N, d'Enfert C, Bougnoux ME, Corti CF, LeibundGut-Landmann S. The intraspecies diversity of C. albicans triggers qualitatively and temporally distinct host responses that determine the balance between commensalism and pathogenicity. Mucosal Immunol. 2017 Feb 8. [Epub ahead of print]

2016

Sem X, Le GT, Tan AS, Tso G, Yurieva M, Liao WW, Lum J, Srinivasan KG, Poidinger M, Zolezzi F, Pavelka N. β-glucan Exposure on the Fungal Cell Wall Tightly Correlates with Competitive Fitness of Candida Species in the Mouse Gastrointestinal Tract. Front Cell Infect Microbiol. 2016 Dec 22;6:186.

Ter Horst R, Jaeger M, Smeekens SP, Oosting M, Swertz MA, Li Y, Kumar V, Diavatopoulos DA, Jansen AF, Lemmers H, Toenhake-Dijkstra H, van Herwaarden AE, Janssen M, van der Molen RG, Joosten I, Sweep FC, Smit JW, Netea-Maier RT, Koenders MM, Xavier RJ, van der Meer JW, Dinarello CA, Pavelka N, Wijmenga C, Notebaart RA, Joosten LA, Netea MG. Host and Environmental Factors Influencing Individual Human Cytokine Responses. Cell. 2016 Nov 3;167(4):1111-1124.e13.

Netea MG, Joosten LA, Li Y, Kumar V, Oosting M, Smeekens S, Jaeger M, Ter Horst R, Schirmer M, Vlamakis H, Notebaart R, Pavelka N, Aguirre-Gamboa RR, Swertz MA, Tunjungputri RN, van de Heijden W, Franzosa EA, Ng A, Graham D, Lassen K, Schraa K, Netea-Maier R, Smit J, de Mast Q, van de Veerdonk F, Kullberg BJ, Tack C, van de Munckhof I, Rutten J, van der Graaf J, Franke L, Hofker M, Jonkers I, Platteel M, Maatman A, Fu J, Zhernakova A, van der Meer JW, Dinarello CA, van der Ven A, Huttenhouwer C, Koenen H, Joosten I, Xavier RJ, Wijmenga C. Understanding human immune function using the resources from the Human Functional Genomics Project. Nat Med. 2016 Aug 4;22(8):831-3.

Teoh F, Pavelka N. How Chemotherapy Increases the Risk of Systemic Candidiasis in Cancer Patients: Current Paradigm and Future Directions. Pathogens. 2016 Jan 15;5(1). 

2015

Liu G, Yong MY, Yurieva M, Srinivasan KG, Liu J, Lim JS, Poidinger M, Wright GD, Zolezzi F, Choi H, Pavelka N, Rancati R. Gene Essentiality Is a Quantitative Property Linked to Cellular Evolvability. Cell. 2015 Dec 3;163(6):1388-99.

Cottier F, Tan AS, Xu X, Wang Y, Pavelka N. MIG1 regulates resistance of Candida albicans against the fungistatic effect of weak organic acids. Eukaryot Cell. 2015 Oct;14(10):1054-61.

Cottier F, Tan AS, Chen J, Lum J, Zolezzi F, Poidinger M, Pavelka N. The Transcriptional Stress Response of Candida albicans to Weak Organic Acids. G3 (Bethesda). 2015 Jan 29;5(4):497-505.

2013

Rancati G, Pavelka N. Karyotypic changes as drivers and catalyzers of cellular evolvability: A perspective from non-pathogenic yeasts. Semin Cell Dev Biol. 2013 Apr;24(4):332-8.

Pavelka N, Rancati G. Never in Neutral: A Systems Biology and Evolutionary Perspective on how Aneuploidy Contributes to Human Diseases. Cytogenet Genome Res. 2013;139(3):193-205.

2012

Cottier F, Pavelka N. Complexity and dynamics of host-fungal interactions. Immunol Res. 2012 Sep;53(1-3):127-35.

 

Zhu J, Pavelka N, Bradford WD, Rancati G, Li R. Karyotypic determinants of chromosome instability in aneuploid budding yeast. PLoS Genet. 2012 May;8(5):e1002719. 

Cottier F, Raymond M, Kurzai O, Bolstad M, Leewattanapasuk W, Jiménez-López C, Lorenz MC, Sanglard D, Váchová L, Pavelka N, Palková Z, Mühlschlegel FA. The bZIP Transcription Factor Rca1p Is a Central Regulator of a Novel CO(2) Sensing Pathway in Yeast. PLoS Pathog. 2012 Jan;8(1):e1002485.

2011

Choi H, Pavelka N. When one and one gives more than two: Challenges and opportunities of integrative omics. Front Gene. 2011; 2:105.

2010

Pavelka N, Rancati G, Li R. Dr Jekyll and Mr Hyde: role of aneuploidy in cellular adaptation and cancer. Curr Opin Cell Biol. 2010 Dec;22(6):809-15. 

Pavelka N, Rancati G, Zhu J, Bradford WD, Saraf A, Florens L, Sanderson BW, Hattem GL, Li R. Aneuploidy confers quantitative proteome changes and phenotypic variation in budding yeast. Nature. 2010 Nov 11;468(7321):321-5.

Fournier ML, Paulson A, Pavelka N, Mosley AL, Gaudenz K, Bradford WD, Glynn E, Li H, Sardiu ME, Fleharty B, Seidel C, Florens L, Washburn MP. Delayed correlation of mRNA and protein expression in rapamycin-treated cells and a role for Ggc1 in cellular sensitivity to rapamycin. Mol Cell Proteomics. 2010 Feb;9(2):271-84.

2009

Mineri R, Pavelka N, Fernandez-Vizarra E, Ricciardi-Castagnoli P, Zeviani M, Tiranti V. How do human cells react to the absence of mitochondrial DNA? PLoS One. 2009 May 28;4(5):e5713. 

2008

Rancati G, Pavelka N, Fleharty B, Noll A, Trimble R, Walton K, Perera A, Staehling-Hampton K, Seidel CW, Li R. Aneuploidy underlies rapid adaptive evolution of yeast cells deprived of a conserved cytokinesis motor. Cell. 2008 Nov 28;135(5):879-93.

Pavelka N, Fournier ML, Swanson SK, Pelizzola M, Ricciardi-Castagnoli P, Florens L, Washburn MP. Statistical similarities between transcriptomics and quantitative shotgun proteomics data. Mol Cell Proteomics. 2008 Apr;7(4):631-44. 

2007

Splendiani A, Brandizi M, Even G, Beretta O, Pavelka N, Pelizzola M, Mayhaus M, Foti M, Mauri G, Ricciardi-Castagnoli P. The genopolis microarray database. BMC Bioinformatics. 2007 Mar 8;8 Suppl 1:S21. 

2006

Pelizzola M, Pavelka N, Foti M, Ricciardi-Castagnoli P. AMDA: an R package for the automated microarray data analysis. BMC Bioinformatics. 2006 Jul 6;7:335

Vizzardelli C, Pavelka N, Luchini A, Zanoni I, Bendickson L, Pelizzola M, Beretta O, Foti M, Granucci F, Nilsen-Hamilton M, Ricciardi-Castagnoli P. Effects of dexamethazone on LPS-induced activationand migration of mouse dendritic cells revealed by a genome-wide transcriptional analysis. Eur J Immunol. 2006 Jun;36(6):1504-15.

2005

Aidinis V, Carninci P, Armaka M, Witke W, Harokopos V, Pavelka N, Koczan D, Argyropoulos C, Thwin MM, Möller S, Waki K, Gopalakrishnakone P, Ricciardi-Castagnoli P, Thiesen HJ, Hayashizaki Y, Kollias G. Cytoskeletal rearrangements in synovial fibroblasts as a novel pathophysiological determinant of modeled rheumatoid arthritis. PLoS Genet. 2005 Oct;1(4):e48.

Aebischer T, Bennett CL, Pelizzola M, Vizzardelli C, Pavelka N, Urbano M, Capozzoli M, Luchini A, Ilg T, Granucci F, Blackburn CC, Ricciardi-Castagnoli P. A critical role for lipophosphoglycan in proinflammatory responses of dendritic cells to Leishmania mexicana. Eur J Immunol. 2005 Feb;35(2):476-86.

Aksoy E, Zouain CS, Vanhoutte F, Fontaine J, Pavelka N, Thieblemont N, Willems F, Ricciardi-Castagnoli P, Goldman M, Capron M, Ryffel B, Trottein F. Double-stranded RNAs from the helminth parasite Schistosoma activate TLR3 in dendritic cells. J Biol Chem. 2005 Jan 7;280(1):277-83.

2004

Pavelka N, Pelizzola M, Vizzardelli C, Capozzoli M, Splendiani A, Granucci F, Ricciardi-Castagnoli P. A power law global error model for the identification of differentially expressed genes in microarray data. BMC Bioinformatics. 2004 Dec17;5:203.

Granucci F, Zanoni I, Pavelka N, Van Dommelen SL, Andoniou CE, Belardelli F, Degli Esposti MA, Ricciardi-Castagnoli P. A contribution of mouse dendritic cell-derived IL-2 for NK cell activation. J Exp Med. 2004 Aug 2;200(3):287-95.

Trottein F, Pavelka N, Vizzardelli C, Angeli V, Zouain CS, Pelizzola M, Capozzoli M, Urbano M, Capron M, Belardelli F, Granucci F, Ricciardi-Castagnoli P. A type I IFN-dependent pathway induced by Schistosoma mansoni eggs in mouse myeloid dendritic cells generates an inflammatory signature. J Immunol. 2004 Mar 1;172(5):3011-7. 

2003

Granucci F, Feau S, Zanoni I, Pavelka N, Vizzardelli C, Raimondi G, Ricciardi-Castagnoli P. The immune response is initiated by dendritic cells via interaction with microorganisms and interleukin-2 production. J Infect Dis. 2003 Jun 15;187 Suppl 2:S346-50.

2001

Granucci F, Vizzardelli C, Pavelka N, Feau S, Persico M, Virzi E, Rescigno M, Moro G, Ricciardi-Castagnoli P. Inducible IL-2 production by dendritic cells revealed by global gene expression analysis. Nat Immunol. 2001 Sep;2(9):88

CV

Full name Norman Pavelka
Work address
Singapore Immunology Network (SIgN)
Agency of Science, Technology and Research (A*STAR)
8A Biomedical Grove, #04-06, Immunos
Singapore 138648
Singapore
Work phone +65 6407 0633
Work fax +65 6464 2057
E-mail norman_pavelka@immunol.a-star.edu.sg
Citizenships Austrian / Italian
Date and place of birth January 11, 1977 – Milan, Italy
Languages Italian / German / English

Work Experience

2011 - present
Principal Investigator
Scientific projects:
SIgN – A*STAR – Singapore
• Evolution of Candida albicans to selective pressures from the host immune system
• Evolution of C. albicans to selective pressures from the host microbiome
• Genome changes underlying antifungal drug resistance in Candida species
2006 - 2011
Postdoctoral Research Associate
Scientific projects:
Prof. Rong Li’s lab – SIMR – Kansas City, MO – USA
• Effects of aneuploidy on the transcriptome, the proteome and the phenome
• Adaptive evolution of budding yeast to genetic perturbations in the cytokinesis pathway
• Application of microarray data analysis methods to proteomics data sets
2001 - 2006
Graduate student
Scientific projects:
Prof. Paola Ricciardi-Castagnoli’s lab – University of Milano-Bicocca – Milan – Italy
• Mass spectrometry-based analysis of the plasma membrane proteome of dendritic cells
• Design, implementation and validation of a method for identifying differentially expressed genes in microarray data, based on a Power Law Global Error Model
• Contribution to the design of a fully automated microarray data analysis pipeline
• Comparative analysis of the transcriptional response of dendritic cells after encounter of two developmental stages of the extra-cellular parasite Schistosoma mansoni
• Contribution to a number of specific collaborations in the field of Functional Genomics approaches to the study of host-pathogen interactions
August 2003
Visiting student
Scientific projects:
Dr. Vassilis Aidinis’ lab – BSRC “Alexander Fleming” – Athens – Greece
• Analysis of a microarray experiment designed to study Rheumatoid Arthritis in two different mouse models
• Integration of the results with data obtained from a subtractive cDNA library
2000 - 2001
Undergraduate student
Scientific projects:
Prof. Paola Ricciardi-Castagnoli’s lab – University of Milano-Bicocca – Milan – Italy
• Transcriptional profiling of the maturation dynamics of dendritic cells after encountering gram-negative bacteria
• Study of the role of interleukin-2 produced by dendritic cells after microbial stimulation in the activation of both the innate and the adaptive immune system
• Study of the role of interleukin-2 produced by dendritic cells after microbial stimulation in the activation of both the innate and the adaptive immune system

Additional Appointments
 
2015 - present 
Visiting Scientist 
Department of Internal Medicine – Radboud University Medical Center – Nijmegen, The Netherlands
2015 - present  Editorial Board Member  Scientific Reports – Nature Publishing Group 
2014 - present  Editorial Board Member  Microbial Pathogenesis – Elsevier 
2013 - present  Adjunct Assistant Professor  School of Biological Sciences – Nanyang Technological University – Singapore 
2011 - present Associate Editor Frontiers in Bioinformatics and Computational Biology


Education & Training
2006
Ph.D. in Immunology
Thesis title:
University of Rome “Tor Vergata” – Rome – Italy
• Integrated Functional Genomics approaches to study the cellular response of dendritic cells to pathogens
2005
Advanced Course
Main subjects:
3rd Computational and Statistical Aspects of Microarray Analysis – Brixen – Italy
• Use of Bioconductor to analyze and interpret microarray data: normalization, quality assessment, gene identification, machine learning and inference for graphs and networks
2001
BS/MS Biotechnology
Thesis title:
University of Milano-Bicocca – Milan – Italy
• Role of dendritic cells-derived interleukin-2 in mouse natural killer cells activation

Honors & Awards
2010 A*STAR Investigatorship (Biomedical Sciences) Agency for Science, Technology and Research – Singapore
2007 Best Oral Presentation by a Postdoctoral Researcher Stowers Research Day 2007 – Kansas City, MO – USA
2006 Novel & Newsworthy Top Pick ASCB Meeting 2006 – San Diego, CA – USA

Memberships to Scientific Societies
2012 - present Faculty Member Singaporean Society for Immunology (SgSI)
2009 - 2011
Member Society for Molecular Biology and Evolution (SMBE)
2006 - 2011 Postdoctoral member American Society of Cell Biology (ASCB)

SOFTWARE

• R package “plgem”, available from: http://www.bioconductor.org
• R package “AMDA”, available from: http://www.genopolis.it

Lab

Back (left to right): Norman Pavelka, Webber Liao (shared with Bioinformatics group), Jose Reales, Fabien Cottier

Front (left to right): Flora Teoh, Gloria Tso, Giang Le, Alrina Tan


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