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

  • December 12, 2022 - November 30, 2027 - Regulation of medullary thymic epithelial cells and thymic central tolerance by Ikaros , Co-Investigator . Sponsor: NIH, Sponsor Award ID: R01AI165829
  • July 25, 2018 - June 30, 2023 - Understanding Ikaros molecular functions for targeted therapies of pre-B ALL , Principal Investigator . Sponsor: NIH, 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, Sponsor Award ID: R01AI127709
  • July 9, 2016 - June 30, 2018 - Mechanism of Ikaros Tumor Suppression in progenitor B cell leukemia , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R21CA209229

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. Podgorica M, Drivet E, Viken JK, Richman A, Vestbøstad J, Szodoray P, Kvam AK, Wik HS, Tjønnfjord GE, Munthe LA, Frietze S, Schjerven H. Transcriptome analysis of primary adult B-cell lineage acute lymphoblastic leukemia identifies pathogenic variants and gene fusions, and predicts subtypes for in depth molecular diagnosis. Eur J Haematol. 2024 Jan 08.  View on PubMed
  2. Kadriye Nehir Cosgun, Mark E Robinson, Salim Oulghazi, Liang Xu, Gang Xiao, Lai N Chan, Jaewoong Lee, Kohei Kume, Etienne Leveille, David Fonseca Arce, Dhruv Khanduja, Niklas Feldhahn, Joo Y. Song, Wing C. Chan, Jianjun Chen, M. Mark Taketo, Hilde Schjerven, Julia Jellusova, Shalin Kothari, Matthew S Davids, Markus Müschen. Repurposing GSK3B Small Molecule Inhibitors for Refractory Lymphoid Malignancies. Blood. 2023 Nov 28; 142(Supplement 1):2818.  View on PubMed
  3. Sin JH, Sucharov J, Kashyap S, Wang Y, Proekt I, Liu X, Parent AV, Gupta A, Kastner P, Chan S, Gardner JM, Ntranos V, Miller CN, Anderson MS, Schjerven H, Waterfield MR. Ikaros is a principal regulator of Aire+ mTEC homeostasis, thymic mimetic cell diversity, and central tolerance. Sci Immunol. 2023 10 27; 8(88):eabq3109.  View on PubMed
  4. Kadriye Nehir Cosgun, Huda Jumaa, Mark E. Robinson, Liang Xu, Gang Xiao, David Fonseca Arce, Dhruv Khanduja, Lai N. Chan, Jaewoong Lee, Hilde Schjerven, Julia Jellusova, Markus Müschen. ß-catenin engages IKZF factors to control lymphopoiesis. The Journal of Immunology. 2023 May 1; 210(1_Supplement):65.09-65.09.  View on PubMed
  5. Cosgun KN, Jumaa H, Robinson ME, Kistner KM, Xu L, Xiao G, Chan LN, Lee J, Kume K, Leveille E, Fonseca-Arce D, Khanduja D, Ng HL, Feldhahn N, Song J, Chan WC, Chen J, Taketo MM, Kothari S, Davids MS, Schjerven H, Jellusova J, Müschen M. Targeted engagement of β-catenin-Ikaros complexes in refractory B-cell malignancies. bioRxiv. 2023 Mar 15.  View on PubMed
  6. Kogut S, Paculova H, Rodriguez P, Boyd J, Richman A, Palaria A, *Schjerven H, *Frietze S. . Ikaros Regulates microRNA Networks in Acute Lymphoblastic Leukemia. Epigenomes. 2022; 6(22):37.  View on PubMed
  7. Kogut S, Paculova H, Rodriguez P, Boyd J, Richman A, Palaria A, Schjerven H, Frietze S. Ikaros Regulates microRNA Networks in Acute Lymphoblastic Leukemia. Epigenomes. 2022 Oct 19; 6(4).  View on PubMed
  8. Boyd J, Rodriguez P, Schjerven H, Frietze S. ssvQC: an integrated CUT&RUN quality control workflow for histone modifications and transcription factors. BMC Res Notes. 2021 Sep 20; 14(1):366.  View on PubMed
  9. Rodriguez PD, Paculova H, Kogut S, Heath J, Schjerven H, Frietze S. . Non-Coding RNA Signatures of B-Cell Acute Lymphoblastic Leukemia. (Review). 2021; 5(22):2683.  View on PubMed
  10. Rodriguez PD, Paculova H, Kogut S, Heath J, Schjerven H, Frietze S. Non-Coding RNA Signatures of B-Cell Acute Lymphoblastic Leukemia. Int J Mol Sci. 2021 Mar 07; 22(5).  View on PubMed
  11. Eugene Park, Jingyu Chen, Andrew Moore, Maurizio Mangolini, Joseph R. Byod, Hilde Schjerven, James C. Williamson, Paul J. Lehner, Michael Leitges, Alexander Egle, Marc Schmidt-Supprian, Seth Frietze, Ingo Ringshausen. Abstract PO-62: Overcoming venetoclax resistance in B-cell malignancies by antagonism of stromal TGF-beta-mediated drug resistance. Blood Cancer Discovery. 2020 Nov 1; 1(3_Supplement):po-62-po-62.  View on PubMed
  12. Princess D Rodriguez, William Howell, Joseph Boyd, Seth Frietze, Hilde Schjerven. Ikaros regulates gene expression programs required for proper BCR-activation in mature B cells. The Journal of Immunology. 2020 May 1; 204(1_Supplement):218.2-218.2.  View on PubMed
  13. 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-β inhibition enhances chemosensitivity in B cell malignancies and overcomes drug resistance. Sci Transl Med. 2020 01 15; 12(526).  View on PubMed
  14. Hilde Schjerven, Princess D Rodriguez, William Howell, Johanne Vestbostad, Seth Frietze, Hilde Schjerven. Ikaros mutations can bypass the requirement for second co-stimulatory signal and lead to break of B-cell tolerance. The Journal of Immunology. 2019 May 1; 202(1_Supplement):179.16-179.16.  View on PubMed
  15. 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. J Exp Med. 2018 10 01; 215(10):2586-2599.  View on PubMed
  16. 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. Nature. 2018 06; 558(7711):E5.  View on PubMed
  17. Hilde Schjerven, Princess Rodriguez, Danielle Hagen, Marit Rasmussen, Etapong F. Ayongaba, Seth Frietze. Ikaros regulates B-cell tolerance. The Journal of Immunology. 2018 May 1; 200(1_Supplement):40.14-40.14.  View on PubMed
  18. Hilde Schjerven, Etapong F. Ayongaba, Princess Rodriguez, Seth Frietze. Ikaros regulates epigenetic and transcriptional programs in progenitor B cell leukemia. The Journal of Immunology. 2018 May 1; 200(1_Supplement):103.26-103.26.  View on PubMed
  19. 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. J Allergy Clin Immunol. 2018 08; 142(2):699-702.e12.  View on PubMed
  20. 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. Cell Rep. 2017 Nov 21; 21(8):2277-2290.  View on PubMed

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