Research Summary

The development of blood cells (hematopoiesis) depends on a complex series of events that involves many regulatory processes. Blood cancer or immunological diseases can develop if these developing cells have loss of function or gain of function mutations in genes that control development, function, growth or survival.

Ikaros (encoded by the IKZF1 gene) is a transcription factor that is required for proper development of many different blood cell lineages. It is also an important tumor suppressor in certain subtypes of pre-B ALL (leukemia) and is implicated in other human immunological diseases through recent GWAS studies.

The overall research interest is in transcriptional regulation in the immune system during development and disease, and the current ongoing and proposed future research is focused on the role of the zinc finger (ZnF) transcription factor Ikaros. Studies use in vitro and in vivo models and also include the use of genome-wide analysis of DNA-binding and chromatin status (ChIP-Seq) as well as gene expression analysis (RNA-Seq). By increasing our knowledge about the molecular mechanism of action of key transcription factors in both normal development and disease, we might guide the development of targeted therapies for diseases where known transcriptional regulators are mutated.

Research Funding

  • July 25, 2018 - June 30, 2023 - Understanding Ikaros molecular functions for targeted therapies of pre-B ALL, Principal Investigator. Sponsor: NIH/NCI, Sponsor Award ID: R01CA230618
  • June 15, 2018 - May 31, 2023 - Role of the transcription factor Ikaros in development of autoimmune disease, Principal Investigator. Sponsor: NIH/NIAID, Sponsor Award ID: R01AI127709
  • July 9, 2016 - June 30, 2018 - Mechanism of Ikaros Tumor Suppression in progenitor B cell leukemia, Principal Investigator. Sponsor: NIH/NCI, Sponsor Award ID: R21CA209229
  • July 25, 2018 - June 30, 2023 - Understanding Ikaros molecular functions for targeted therapies of pre-B ALL, Principal Investigator. Sponsor: NIH/NCI, Sponsor Award ID: R01CA230618

Education

Norwegian University of Sports, 06/92, One-Year Study
Norwegian University of Science and Technology (NTNU), Department of Chemical Engineering, M.Sc. “Sivilingeniør” (Master of Science), 06/96, Biotechnology
One year exchange student at University of Wisconsin, Madison, 06/96, One year exchange Study
University of Oslo, Norway, Faculty of Medicine, Ph.D., 06/03, Molecular Immunology

Honors & Awards

  • 1999
    Ph.D. scholarship , Norwegian Cancer Society
  • 2003
    Postdoctoral Fellow Grant , Norwegian Research Council
  • 2012
    Early Career Faculty Travel Grant, American Association of Immunologists (AAI)
  • 2015
    Early Career Faculty Travel Grant., American Association of Immunologists (AAI)
  • 2015 - 2107
    ANRF Scholar
  • 2015-2017
    Hellman Fellow

Selected Publications

  1. Park E, Chen J, Moore A, Mangolini M, Santoro A, Boyd JR, Schjerven H, Ecker V, Buchner M, Williamson JC, Lehner PJ, Gasparoli L, Williams O, Bloehdorn J, Stilgenbauer S, Leitges M, Egle A, Schmidt-Supprian M, Frietze S, Ringshausen I Stromal cell protein kinase C-ß inhibition enhances chemosensitivity in B cell malignancies and overcomes drug resistance.  View on PubMed
  2. Fistonich C, Zehentmeier S, Bednarski JJ, Miao R, Schjerven H, Sleckman BP, Pereira JP Cell circuits between B cell progenitors and IL-7+ mesenchymal progenitor cells control B cell development.  View on PubMed
  3. Chan LN, Chen Z, Braas D, Lee JW, Xiao G, Geng H, Cosgun KN, Hurtz C, Shojaee S, Cazzaniga V, Schjerven H, Ernst T, Hochhaus A, Kornblau SM, Konopleva M, Pufall MA, Cazzaniga G, Liu GJ, Milne TA, Koeffler HP, Ross TS, Sánchez-García I, Borkhardt A, Yamamoto KR, Dickins RA, Graeber TG, Müschen M Author Correction: Metabolic gatekeeper function of B-lymphoid transcription factors.  View on PubMed
  4. Van Nieuwenhove E, Garcia-Perez JE, Helsen C, Rodriguez PD, van Schouwenburg PA, Dooley J, Schlenner S, van der Burg M, Verhoeyen E, Gijsbers R, Frietze S, Schjerven H, Meyts I, Claessens F, Humblet-Baron S, Wouters C, Liston A A kindred with mutant IKAROS and autoimmunity.  View on PubMed
  5. Ye J, Qiu J, Bostick JW, Ueda A, Schjerven H, Li S, Jobin C, Chen ZE, Zhou L The Aryl Hydrocarbon Receptor Preferentially Marks and Promotes Gut Regulatory T Cells.  View on PubMed
  6. Lai N. Chan, Zhengshan Chen, Gang Xiao, Jae Woong Lee, Kadriye Nehir Cosgun, Huimin Geng, Valeria Cazzaniga, Hilde Schjerven, Ross A. Dickins, Markus Muschen Abstract 93: Transcriptional control of glucocorticoid responses in leukemia.  View on PubMed
  7. Katerndahl CDS, Heltemes-Harris LM, Willette MJL, Henzler CM, Frietze S, Yang R, Schjerven H, Silverstein KAT, Ramsey LB, Hubbard G, Wells AD, Kuiper RP, Scheijen B, van Leeuwen FN, Müschen M, Kornblau SM, Farrar MA Antagonism of B cell enhancer networks by STAT5 drives leukemia and poor patient survival.  View on PubMed
  8. Chan LN, Chen Z, Braas D, Lee JW, Xiao G, Geng H, Cosgun KN, Hurtz C, Shojaee S, Cazzaniga V, Schjerven H, Ernst T, Hochhaus A, Kornblau SM, Konopleva M, Pufall MA, Cazzaniga G, Liu GJ, Milne TA, Koeffler HP, Ross TS, Sánchez-García I, Borkhardt A, Yamamoto KR, Dickins RA, Graeber TG, Müschen M Metabolic gatekeeper function of B-lymphoid transcription factors.  View on PubMed
  9. Schjerven H, Ayongaba EF, Aghajanirefah A, McLaughlin J, Cheng D, Geng H, Boyd JR, Eggesbø LM, Lindeman I, Heath JL, Park E, Witte ON, Smale ST, Frietze S, Müschen M Genetic analysis of Ikaros target genes and tumor suppressor function in BCR-ABL1+ pre-B ALL.  View on PubMed
  10. Li S, Heller JJ, Bostick JW, Lee A, Schjerven H, Kastner P, Chan S, Chen ZE, Zhou L Ikaros Inhibits Group 3 Innate Lymphoid Cell Development and Function by Suppressing the Aryl Hydrocarbon Receptor Pathway.  View on PubMed
  11. Arenzana TL, Schjerven H, Smale ST Regulation of gene expression dynamics during developmental transitions by the Ikaros transcription factor.  View on PubMed
  12. Song C, Gowda C, Pan X, Ding Y, Tong Y, Tan BH, Wang H, Muthusami S, Ge Z, Sachdev M, Amin SG, Desai D, Gowda K, Gowda R, Robertson GP, Schjerven H, Muschen M, Payne KJ, Dovat S Targeting casein kinase II restores Ikaros tumor suppressor activity and demonstrates therapeutic efficacy in high-risk leukemia.  View on PubMed
  13. Buchner M, Park E, Geng H, Klemm L, Flach J, Passegué E, Schjerven H, Melnick A, Paietta E, Kopanja D, Raychaudhuri P, Müschen M Identification of FOXM1 as a therapeutic target in B-cell lineage acute lymphoblastic leukaemia.  View on PubMed
  14. Shojaee Seyedmehdi, Zhengshan Chen, Maike Buchner, Christian Hurtz, Huimin Geng, Hilde Schjerven, Lai N Chan, Phillip Koeffler, Cheryl L. Willman, Stephen Hunger, Sinisa Dovat, Elisabeth Paietta, Wolf-Karsten Hofmann, Ari M Melnick, Warren S. Alexander, Steven M. Kornblau, Markus Muschen Erk and Stat5 Feedback Control Enables Pre-B Cell Transformation and Represents a Therapeutic Target in Acute Lymphoblastic Leukemia.  View on PubMed
  15. Seyedmehdi Shojaee, Valeria Cazzaniga, Hilde Schjerven, Maike Buchner, Christian Hurtz, Huimin Geng, Andreas Hochhaus, Giovanni Cazzaniga, Ari M Melnick, Steven M. Kornblau, Thomas G Graeber, Markus Muschen PTEN Is Essential for Normal Cytokine Signaling and Oncogenic Transformation of Pre-B Cells.  View on PubMed
  16. Heller JJ, Schjerven H, Li S, Lee A, Qiu J, Chen ZM, Smale ST, Zhou L Restriction of IL-22-producing T cell responses and differential regulation of regulatory T cell compartments by zinc finger transcription factor Ikaros.  View on PubMed
  17. Schjerven H, McLaughlin J, Arenzana TL, Frietze S, Cheng D, Wadsworth SE, Lawson GW, Bensinger SJ, Farnham PJ, Witte ON, Smale ST Selective regulation of lymphopoiesis and leukemogenesis by individual zinc fingers of Ikaros.  View on PubMed
  18. Jennifer Heller, Hilde Schjerven, Ju Qiu, Aileen Lee, Stephen Smale, Liang Zhou 118 Modulation of Treg and Th17 fate decision by selective ikaros zinc fingers.  View on PubMed
  19. Reynaud D, Demarco IA, Reddy KL, Schjerven H, Bertolino E, Chen Z, Smale ST, Winandy S, Singh H Regulation of B cell fate commitment and immunoglobulin heavy-chain gene rearrangements by Ikaros.  View on PubMed
  20. Damien REYNAUD, Karen REDDY, Hilde SCHJERVEN, Chauncey SPOONER, Eric BERTOLINO, Stephen T SMALE, Susan WINANDY, Harinder SINGH Regulation of B cell fate specification and VH gene rearrangements by Ikaros.  View on PubMed

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