Hilde Schjerven, PhD
UCSF
Laboratory Medicine, Box 0451
513 Parnassus Avenue, Room S-1479
San Francisco, CA 94143
United States
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.
- 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 May;112(5):731-742. doi: 10.1111/ejh.14164. Epub 2024 Jan 8. PMID: 38192186; PMCID: PMC10990798.
- 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 Oct 27;8(88):eabq3109. doi: 10.1126/sciimmunol.abq3109. Epub 2023 Oct 27. PMID: 37889983;
PMCID: PMC11433069. - 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 [Preprint]. 2023 Mar 15:2023.03.13.532152. doi: 10.1101/2023.03.13.532152. PMID: 36993619; PMCID: PMC10054980.
- 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):37. doi: 10.3390/epigenomes6040037. PMID: 36278683; PMCID: PMC9624360.
For a complete list through PubMed:
- Hellman Fellow