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Education

Andreas Lennartsson has a master in Biotechnology from Lund University in Sweden. He did his PhD in Experimental hematology also at Lund University. After his PhD he contunied to the OMICS center at RIKEN in JAPAN for post-doc training in Piero Carninci's group. He carried out his second post-doc i Karl Ekwall's group at Karolinska Institute, where he is now leading a sub-group in Prof. Ekwall's laboratory.

Research description

Epigenetic regulation of myelopoiesis and its role in acute myeloid leukemia

Acute myeloid leukemia (AML) is the most common form of acute leukemia. It is characterised by high mortality with a long-term survival of only 15%. Currently the majority of treatments for AML are cytotoxic drugs with poor specificity. In order to develop safer therapeutics and more effective drugs, better understanding of the mechanisms that underlie the disease are needed.

My research aims at understanding the epigenetic regulatory mechanisms of myelopoiesis and how they regulate multi-potency and differentiation. The importance of epigenetic regulation in myelopoiesis is demonstrated by the finding of mutation in several epigenetic regulating genes in acute myeloid leukemia (AML). To be able to interpret the abnormal epigenetic regulations in AML, it is essential to first characterize and understand the epigenetic regulation during normal myelopoiesis. We aim to identify epigenetic regulatory enzymes that are important to keep the cell in a multi-potent stage, regulate lineage choice and differentiation. Their contribution to AML development and maintenance is also  analyzed. 

Another focus is on enhancers and how they regulate the transcriptome during normal and malign myelopoiesis. A key component to cell identity is the enhancer activity and how they control cell specific transcriptome. We recently showed that DNA demethylation coincide with enhancer activity during granulopoiesis (Rönnerblad et al 2014 Blood). 

Our aims are to:

 1. Map how the epigenetic modifications that are connected to enhancers are disturbed in acute myeloid leukemic stem cells.

 2. Characterize the effect the deregulated epigenetic modifications have on enhancer activity and on the transcriptional program that creates and stabilize multi-potency.  

3. Identify key epigenetic factors that regulate enhancer activity and multi-potency in hematopoietic stem cells.

4. Investigate whether these epigenetic factors are deregulated in AML and how they contribute to the leukemic phenotype.

 5. Analyze the role of the identified epigenetic factors have in drug resistance.

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