Joanne Attema, Ph.D. Assistant Professor
Joanne.Attema@med.lu.se
+46 (0) 46 222 3338
Students:
Mr. Holger Weishaupt, PhD student
Holger.Weishaupt@med.lu.se
+46 (0) 46 222 0312
Our research aims at understanding the epigenetic events involved in regulating normal and malignant blood cell development with an emphasis on hematopoietic stem cells and early differentiating progenitor subsets. These immature cells are responsible for generating all of the mature cell types (approx. 10) that constitute the blood system.
Epigenetic regulation in blood cell development
Epigenetics is the study of modifications to the chromatin fibre that controls the packaging and function of the genome. These changes are defined from a molecular biology perspective as being reversible without alteration of the DNA sequence, yet they can alter gene expression programs to encourage certain cellular fates. Such events have been found to be central for most cell biological processes, including hematopoietic cell development, and thus serve to propagate and maintain appropriate cellular identity. In animal cells, DNA can be modified by methylation of cytosine residues in CpG dinucleotides, and the N-terminal tails of histone proteins are subject to a wide range of different modifications, including acetylation, methylation, phosphorylation and ubiquitylation. All of these chemical changes seem to have a substantial influence on chromatin structure and gene function, which differs depending on the type and location of the modification. One of our primary and long standing interests in the laboratory is elucidate such processes in hematopoietic stem cell lineage commitment.
Epigenetic regulation in hematopoietic malignancies
In recent years, it has become increasingly recognized that epigenetic alterations play a major role in driving malignant transformation and cancer progression. These changes can be collectively referred to as “epigenetic lesions” that disrupt the normal transcriptional programming of a gene and combinatorial gene networks. A major goal of our research is to uncover the aberrant epigenetic lesions associated with haematological malignancies including acute myeloid leukemia and myeloproliferative disease. In the context of such disorders, we are examining signalling and transcription factor oncogenic mutations using relevant mouse models and human clinical samples. Ultimately, we hope to identify novel gene targets and pathways for the development of improved therapies in the clinic.
Our technology platforms
We use a combination of technically advanced molecular and cell biology approaches to address our various questions in stem cell biology. Our recent work has lead to significant and important advances in scaling down methods to probe chromatin states of rare populations of murine hematopoietic stem cells (Attema et al., 2007 PNAS). Our efforts in technology development are aimed at further refining and simplifying chromatin-based global methods for their application to rare primary cell subsets including leukemia target cells (Weishaupt et al., 2010). We utilize a range of cell biology assays including in vitro culture assays, transplantation assays to assess stem and progenitor cell function, functional screens using viral vectors for target gene overexpression and knockdown, transgenic and knockout mouse models. Our research is assisted by the continuous development of databases for bioinformatic analysis of the large datasets generated in our projects.
If you are interested in pursuing our exciting and new PhD or postdoctoral research projects with us, please contact Dr. Joanne Attema (Joanne.Attema@med.lu.se) and send through a copy of your CV and contacts for references.
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Last modified: 2012-02-08
