Mafalda Araujo Pereira

Picture of Mafalda Araujo Pereira

Name: Mafalda Araújo Pereira

Nationality: Portuguese

Academic Background: Master’s degree in Molecular oncology

Project Title: Uncovering the role of KDM5C during normal hematopoiesis

Project Background: Hematopoiesis is responsible for forming all cellular components of the blood. It relies on a well-regulated balance between self-renewal and differentiation of Hematopoietic Stem Cells (HSCs) to maintain the lifelong regeneration of blood cells. This homeostasis is highly dependent on regulated gene expression both at transcriptional and post-transcriptional level.

An important determinant of transcriptional regulation is deposition of post-translational histone-modifications (histone marks) on gene regulatory elements. Consequently, the enzymes regulating these marks are crucial determinants of cellular identity.

We have previously conducted an shRNA screen to identify the histone demethylase KDM5C as a tumor suppressor in Acute Myeloid Leukemia (AML). KDM5c catalyses the conversion of Histone 3 Lysine 4 (H3K4) into a mono-methylated state, and we show that this activity keeps genes important for Leukemic Stem Cells (LSCs) in a repressed state.

To assess the role of KDM5C in normal hematopoiesis, we have generated a conditional Kdm5c knock-out (KO) mouse-strain. Preliminary data shows that hematopoietic Kdm5c KO perturbs normal hematopoiesis via reduced HSC-fitness.

Project Aim:  In this PhD project, our aim is to gain insight into the mechanisms underlying the above-described preliminary findings regarding the functions of KDM5C in normal hematopoiesis. To meet this aim, we propose a project, which is divided into the following 3 Work Packages (WP):

  • WP1 – Phenotypic characterization of Kdm5c-KO mouse strain
  • WP2 – Gene expression analyses
  • WP3 – Identification of KDM5C targets

 

Expected Outcome:  We believe that this project will increase the understanding of the mechanistic basis of the role of KDM5C in hematopoiesis and thus of the regulation of this crucial physiological process. The outcome of these analyses will allow us to identify specific cell populations and molecular targets relying on KDM5c activity.

Contact:  Mafalda.araujo@finsenlab.dk