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.
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.
Mutations in histone modulators are associated with prolonged survival during azacitidine therapy
EpiFactors: a comprehensive database of human epigenetic factors and complexes
Database : the journal of biological databases and curation 2015;2015():bav067-
Epigenetic aberrations in acute myeloid leukemia: Early key events during leukemogenesis
Experimental hematology 2015;43(8):609-24
Remodeling of retrotransposon elements during epigenetic induction of adult visual cortical plasticity by HDAC inhibitors
Epigenetics & chromatin 2015;8():55-
Technical Advance: Transcription factor, promoter, and enhancer utilization in human myeloid cells
JOURNAL OF LEUKOCYTE BIOLOGY 2015;97(5):985-995
The Roles of SNF2/SWI2 Nucleosome Remodeling Enzymes in Blood Cell Differentiation and Leukemia
BIOMED RESEARCH INTERNATIONAL 2015;:347571-
Transcribed enhancers lead waves of coordinated transcription in transitioning mammalian cells
Science (New York, N.Y.) 2015;347(6225):1010-4
An atlas of active enhancers across human cell types and tissues
A promoter-level mammalian expression atlas
Differential methylation in CN-AML preferentially targets non-CGI regions and is dictated by DNMT3A mutational status and associated with predominant hypomethylation of HOX genes
High-throughput transcription profiling identifies putative epigenetic regulators of hematopoiesis
microRNA-34b/c on chromosome 11q23 is aberrantly methylated in chronic lymphocytic leukemia
The DEK oncoprotein binds to highly and ubiquitously expressed genes with a dual role in their transcriptional regulation
Molecular cancer 2014;13():215-
Allele-specific programming of Npy and epigenetic effects of physical activity in a genetic model of depression
Translational psychiatry 2013;3():e255-
Leukemia associated mutant Wilms' tumor gene 1 protein promotes expansion of human hematopoietic progenitor cells
Leukemia research 2013;37(10):1341-9
Antidepressant treatment is associated with epigenetic alterations in the promoter of P11 in a genetic model of depression
INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY 2012;15(5):669-79
Epigenetic alterations related to early life stressful events
ACTA NEUROPSYCHIATRICA 2012;24(5):253-254
Histone modification patterns and epigenetic codes
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS 2009;1790(9):863-8
The transcriptional network that controls growth arrest and differentiation in a human myeloid leukemia cell line
NATURE GENETICS 2009;41(5):553-62
All-trans retinoic acid-induced expression of bactericidal/permeability-increasing protein (BPI) in human myeloid cells correlates to binding of C/EBP beta and C/EBP epsilon to the BPI promoter
JOURNAL OF LEUKOCYTE BIOLOGY 2006;80(1):196-203
Functional and biochemical characterization of epithelial bactericidal/permeability-increasing protein
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY 2006;290(3):G557-67
A murine antibacterial ortholog to human bactericidal/permeability-increasing protein (BPI) is expressed in testis, epididymis, and bone marrow
JOURNAL OF LEUKOCYTE BIOLOGY 2005;77(3):369-77
Bactericidal Permeability-increasing protein (BPI), a potentially important facet of innate immunity in intestinal epithelial cells
FASEB JOURNAL 2005;19(4):A498-A498
AML-1, PU.1, and Sp3 regulate expression of human bactericidal/permeability-inereasing protein
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 2003;311(4):853-63
A murine orthologue to human bactericidal/permeability increasing protein (BPI) is expressed in bone marrow, testis, and epididymis and possesses antibacterial activity towards gram-negative bacteria.
Myeloid expression of the BPI (bactericidal permeability increasing protein) gene is regulated by AML1, Sp3, PU.1and C/EBP
EXPERIMENTAL HEMATOLOGY 2003;31(7):126-126
Myeloid expression of the BPI (bactericidal/permeability increasing protein) gene is regulated by AML1 and C/EBP.
Characterisation of the proximal promoter of human cathepsin G.