The continued production of functional blood cells is based on maturation of multipotent progenitors gradually loosing lineage potentials to end up as progenitor cells committed into a defined category of blood cells. This process involves an intricate interplay between transcription factor networks acting to drive development by activation of transcriptional programs but also to impose epigenetic silencing of genes associated with alternative blood cell types to ensure stable lineage commitment. The maturation process is further under the influence of external regulatory cues provided by the microenvironment in the bone marrow.
Our laboratory focuses the research on understanding the molecular processes that regulate B-lymphocyte differentiation and lineage commitment as well as the disruption of these networks underlying malignant transformation in leukemia (B-ALL) - one of the most common causes of childhood malignancies.
One of our major lines of investigations focuses on the unraveling of how the interplay between transcription factors and external signals are integrated to drive cell differentiation and lineage commitment. To this end we have identified several auto-regulatory, partially overlapping feed forward loops that interconnect to drive differentiation. This process progresses through a specification route recognised by the activation of B-lineage restricted genes into a second stage where all alternative lineage potentials are lost. The transcription factor loops are interconnected to cellular signalling creating a highly complex network of events. We are currently analyzing the mechanisms of epigenetic activation and silencing of genes associated with defined steps of development with the long-term aim to understand the details of the molecular regulation of lymphocyte commitment.
- To unravel the molecular mechanisms underlying cell specification and differentiation in normal and malignant lymphocyte development.
- To understand the molecular interplay between leukemia cells and the microenvironment in malignant disease
While the genetic alterations underlying the formation of leukemia are becoming rather well understood, it remains a challenge to understand how these mutations impact the normal growth and differentiation of progenitor cells in the BM. cells. Hence, our research aims to increase the understanding of the complex interactions that drive normal cell differentiation as well as malignant transformation. This knowledge can be used to understand the complex molecular interplay that drives the transformation process.
(name linked to profile in Lund University research portal)
Principal Investigator, Mikael [dot] Sigvardsson [at] med [dot] lu [dot] se
Research Scientist, Christina [dot] Jensen [at] med [dot] lu [dot] se
Research Scientist, Jonas [dot] Ungerback [at] med [dot] lu [dot] se
Research Engineer, Maria [dot] Malmberg [at] med [dot] lu [dot] se
PhD student, Johanna [dot] Tingvall-Gustafsson [at] med [dot] lu [dot] se