Dr Alena Pance, PhD; MSc; | Senior Staff Scientist

Pance, Alena

My main work centres on the development of stem cell-based strategies to study the host contribution to malaria infection. This study includes genome editing, haematopoietic differentiation and malaria infection. Other areas of interest are transcriptional regulation and cell differentiation as well as immunology, particularly the innate immune response.

The most clinically relevant stage of malaria infection is the parasite expansion in the blood, which is dependent on multiple receptor-ligand cell surface interactions. We have used a piggy-bac random mutagenesis approach for the identification of the parasite factors implicated in invasion and survival in collaboration with John Adams (https://sangerinstitute.wordpress.com/2013/10/08/target-practice-with-malaria-parasites/). Identification of host receptors is more difficult because erythrocytes are enucleated and therefore genetic approaches are not possible so many receptors remain unknown. To overcome this limitation, we are using stem cells to introduce genomic modifications that will be carried by the erythrocytes differentiated from these stem cells through our protocol and challenged with the parasite (see example figure below). This project will allow us to understand the interaction between the parasite and its host better, which we hope will contribute to the fight against this disease. Within this project, I collaborate with Cedric Ghevaert, in Haematology Cambridge, to engineer human stem cell lines for haematopoietic differentiation.

I am also interested in the differentiation process and its regulation, mainly at the transcriptional level. My work on transcriptional regulation has been focused on the inducible nitric oxide synthase (iNOS), which is part of the innate immune response and plays an important role in infectious disease as well as in cancer. We identified a novel regulatory element in the iNOS promoter and demonstrated that Oct-1 binding to it controls expression of iNOS by PolII recruitment and pausing (see the model below). More recently we showed that some cells express another member of this family of transcription factors, Oct-2, which forms a higher order complex on the promoter preventing PolII recruitment thereby repressing iNOS.

I also collaborate with Tony Jackson, in Biochemistry Cambridge, on a series of cell biology studies (https://sangerinstitute.wordpress.com/2014/10/13/the-life-and-death-of-a-b-cell/), to understand intracellular trafficking and chemotaxis.

Publications

  • A Stem Cell Strategy Identifies Glycophorin C as a Major Erythrocyte Receptor for the Rodent Malaria Parasite Plasmodium berghei.

    Yiangou L, Montandon R, Modrzynska K, Rosen B, Bushell W et al.

    PloS one 2016;11;6;e0158238

  • Oct-1, to go or not to go? That is the PolII question.

    Pance A

    Biochimica et biophysica acta 2016;1859;6;820-4

  • Oct-2 forms a complex with Oct-1 on the iNOS promoter and represses transcription by interfering with recruitment of RNA PolII by Oct-1.

    Bentrari F, Chantôme A, Knights A, Jeannin JF and Pance A

    Nucleic acids research 2015;43;20;9757-65

  • Oct-1 cooperates with the TATA binding initiation complex to control rapid transcription of human iNOS.

    Reveneau S, Petrakis TG, Goldring CE, Chantôme A, Jeannin JF and Pance A

    Cellular and molecular life sciences : CMLS 2012;69;15;2609-19

  • Tailoring the models of transcription.

    Pance A

    International journal of molecular sciences 2013;14;4;7583-97

  • Atypical mitogen-activated protein kinase phosphatase implicated in regulating transition from pre-S-Phase asexual intraerythrocytic development of Plasmodium falciparum.

    Balu B, Campbell C, Sedillo J, Maher S, Singh N et al.

    Eukaryotic cell 2013;12;9;1171-8

  • CCR4-associated factor 1 coordinates the expression of Plasmodium falciparum egress and invasion proteins.

    Balu B, Maher SP, Pance A, Chauhan C, Naumov AV et al.

    Eukaryotic cell 2011;10;9;1257-63

  • A role for the transcriptional repressor REST in maintaining the phenotype of neurosecretory-deficient PC12 cells.

    Pance A, Livesey FJ and Jackson AP

    Journal of neurochemistry 2006;99;5;1435-44

  • Chemosensitization by a non-apoptogenic heat shock protein 70-binding apoptosis-inducing factor mutant.

    Schmitt E, Parcellier A, Gurbuxani S, Cande C, Hammann A et al.

    Cancer research 2003;63;23;8233-40

  • HSP27 is a ubiquitin-binding protein involved in I-kappaBalpha proteasomal degradation.

    Parcellier A, Schmitt E, Gurbuxani S, Seigneurin-Berny D, Pance A et al.

    Molecular and cellular biology 2003;23;16;5790-802

  • Hemopoietic-specific Sf3b1-K700E knock-in mice display the splicing defect seen in human MDS but develop anemia without ring sideroblasts.

    Mupo A, Seiler M, Sathiaseelan V, Pance A, Yang Y et al.

    Leukemia 2017;31;3;720-727

  • Oct-2 forms a complex with Oct-1 on the iNOS promoter and represses transcription by interfering with recruitment of RNA PolII by Oct-1.

    Bentrari F, Chantôme A, Knights A, Jeannin JF and Pance A

    Nucleic acids research 2015;43;20;9757-65

  • Atypical mitogen-activated protein kinase phosphatase implicated in regulating transition from pre-S-Phase asexual intraerythrocytic development of Plasmodium falciparum.

    Balu B, Campbell C, Sedillo J, Maher S, Singh N et al.

    Eukaryotic cell 2013;12;9;1171-8

  • Tailoring the models of transcription.

    Pance A

    International journal of molecular sciences 2013;14;4;7583-97

  • Oct-1 cooperates with the TATA binding initiation complex to control rapid transcription of human iNOS.

    Reveneau S, Petrakis TG, Goldring CE, Chantôme A, Jeannin JF and Pance A

    Cellular and molecular life sciences : CMLS 2012;69;15;2609-19

  • CCR4-associated factor 1 coordinates the expression of Plasmodium falciparum egress and invasion proteins.

    Balu B, Maher SP, Pance A, Chauhan C, Naumov AV et al.

    Eukaryotic cell 2011;10;9;1257-63

  • Secretory granule biogenesis in sympathoadrenal cells: identification of a granulogenic determinant in the secretory prohormone chromogranin A.

    Courel M, Rodemer C, Nguyen ST, Pance A, Jackson AP et al.

    The Journal of biological chemistry 2006;281;49;38038-51

  • A role for the transcriptional repressor REST in maintaining the phenotype of neurosecretory-deficient PC12 cells.

    Pance A, Livesey FJ and Jackson AP

    Journal of neurochemistry 2006;99;5;1435-44

  • Nitric oxide and hormones in breast cancer: allies or enemies?

    Pance A

    Future oncology (London, England) 2006;2;2;275-88

  • Distinct domains of the sodium channel beta3-subunit modulate channel-gating kinetics and subcellular location.

    Yu EJ, Ko SH, Lenkowski PW, Pance A, Patel MK and Jackson AP

    The Biochemical journal 2005;392;Pt 3;519-26

  • Progesterone enhances cytokine-stimulated nitric oxide synthase II expression and cell death in human breast cancer cells.

    Bentrari F, Arnould L, Jackson AP, Jeannin JF and Pance A

    Laboratory investigation; a journal of technical methods and pathology 2005;85;5;624-32

  • Casein kinase II-mediated phosphorylation of NF-kappaB p65 subunit enhances inducible nitric-oxide synthase gene transcription in vivo.

    Chantôme A, Pance A, Gauthier N, Vandroux D, Chenu J et al.

    The Journal of biological chemistry 2004;279;23;23953-60

  • Kinetics of tumor cell apoptosis and immune cell activation during the regression of tumors induced by lipid A in a rat model of colon cancer.

    Larmonier CB, Arnould L, Larmonier N, Baumann S, Moutet M et al.

    International journal of molecular medicine 2004;13;3;355-61

  • Chemosensitization by a non-apoptogenic heat shock protein 70-binding apoptosis-inducing factor mutant.

    Schmitt E, Parcellier A, Gurbuxani S, Cande C, Hammann A et al.

    Cancer research 2003;63;23;8233-40

  • Heat shock protein 70 binding inhibits the nuclear import of apoptosis-inducing factor.

    Gurbuxani S, Schmitt E, Cande C, Parcellier A, Hammann A et al.

    Oncogene 2003;22;43;6669-78

  • HSP27 is a ubiquitin-binding protein involved in I-kappaBalpha proteasomal degradation.

    Parcellier A, Schmitt E, Gurbuxani S, Seigneurin-Berny D, Pance A et al.

    Molecular and cellular biology 2003;23;16;5790-802

  • Antitumoral effects of lipid A: preclinical and clinical studies.

    Pance A, Reisser D and Jeannin JF

    Journal of investigative medicine : the official publication of the American Federation for Clinical Research 2002;50;3;173-8

  • A repressor in the proximal human inducible nitric oxide synthase promoter modulates transcriptional activation.

    Pance A, Chantome A, Reveneau S, Bentrari F and Jeannin JF

    FASEB journal : official publication of the Federation of American Societies for Experimental Biology 2002;16;6;631-3

  • Mechanisms of the antitumoral effect of lipid A.

    Reisser D, Pance A and Jeannin JF

    BioEssays : news and reviews in molecular, cellular and developmental biology 2002;24;3;284-9

  • Heat shock enhances transcriptional activation of the murine-inducible nitric oxide synthase gene.

    Goldring CE, Reveneau S, Chantome A, Pance A, Fleury C et al.

    FASEB journal : official publication of the Federation of American Societies for Experimental Biology 2000;14;15;2393-5

  • A PC12 variant lacking regulated secretory organelles: aberrant protein targeting and evidence for a factor inhibiting neuroendocrine gene expression.

    Pance A, Morgan K, Guest PC, Bowers K, Dean GE et al.

    Journal of neurochemistry 1999;73;1;21-30

  • Detection of specific antibodies to Plasmodium falciparum in blood bank donors from malaria-endemic and non-endemic areas of Venezuela.

    Contreras CE, Pance A, Marcano N, González N and Bianco N

    The American journal of tropical medicine and hygiene 1999;60;6;948-53

Career/Research Highlights

Pance, Alena
Alena's Timeline
2008

Staff scientist, Sanger Institute UK

2005

Research associate, Department of Biochemistry, Cambridge UK

2002

Marie Curie Individual Fellow, Biochemistry Cambridge UK

1998

Research Associate, Faculty of Medicine Universite de Bourgogne France

PhD defended, Cambridge UK