Hilde Schjerven, PhD

Proper blood cell (hematopoietic) development is essential for life and is controlled by a fine-tuned regulatory network that is still incompletely understood. The critical importance of this is underscored by the wide range of diseases that can arise due to defects in the regulation of hematopoiesis, including immunodeficiency, autoimmunity and blood cell cancers.

The Schjerven lab studies normal and malignant blood cell development with a focus on transcriptional regulation, and the molecular mechanisms underlying how key genes regulate cell fate decisions, and how mutations in these key regulatory factors can cause disease. The transcription factor Ikaros, encoded by the IKZF1 gene, is a major focus of ongoing work. Due to the many roles of Ikaros in blood cell development and function, the lab has several diverse and complementary research projects.  

Ongoing projects and research directions:
Hematopoietic development: We use mutant mouse models and multi-color flow cytometry to study how specific genes regulate the development of different immune cell lineages. Ikaros, encoded by the Ikzf1 gene, is required for B-cell development, and also important for proper development of several other hematopoietic cell lineages, but the mechanisms underlying these critical developmental functions are not fully understood. In humans, mutations in IKZF1 is associated with immunodeficiency, autoimmunity as well as leukemia. Increased understanding of normal hematopoietic development, and the molecular mechanisms underlying cell fate decision is important both in regards to basic biology, but also in regards to understanding hematological diseases. 

Methods and Approach: In addition to classical molecular biology, cell culture and immunological techniques, we also utilize complex and state-of-the-art tools to address our biological questions. This includes mutant mouse models for in vivo or ex vivo studies, multi-parameter flow cytometry and FACS sorting, genome-wide profiling by next-generation sequencing (RNA-Seq, ATAC-Seq, ChIP-Seq) and gene manipulation by CRISPR/Cas9 or dCas9-mediated CRISPRi. We welcome collaborations and adaptations of new methods that can help us address our biological questions.

Additional research directions: Ikaros is known to be highly alternative spliced during blood cell development, but the functional importance of this is not well understood. Ikaros is a zinc finger (ZnF) transcription factor that is known to bind and recruit different chromatin modifying complexes, but the identity of these complexes, and how they might vary during different stages of blood cell development, is unknown. Furthermore, Ikaros is found to be mutated in patients with Autoimmunity, and we study the role of Ikaros in B-cell development and in B-cell tolerance, as well as in other cell lineages that are relevant to autoimmunity. Ikaros is also found to be an important tumor suppressor in leukemia, which is another area of study in our lab. We have recently embarked on studies of non-coding RNA and their role in normal and malignant blood cell development and function. Non-coding RNA is a pioneering field, where the many biological functions of these RNA molecules are just starting to be unraveled. Last, but not least, both developing blood cells and leukemic cells are dependent upon, and interact with their in vivo microenvironment, adapting to and also influencing the healthy cells of the host. We welcome lab members and collaborators interested in any of the above aspects.