Konstantinos Anastassiadis - Mechanisms that control the totipotency and differentiation of mouse ES cells

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Previous and current research

The research interest in my lab is to unravel the molecular pathways that regulate self-renewal and lineage commitment of stem cells and the molecular mechanisms that are involved in cellular reprogramming. We work with mouse and human embryonic stem cells (mES, hES), neural stem cells (NSCs), mesenchymal stromal cells (MSCs) and induced pluripotent stem cells (iPS). My lab is also focusing on the development of genetic engineering tools that can be used to address the above questions. A short overview of the projects in my lab is presented below:

1) Development of new genetic engineering tools. We generated deleter and reporter mice for a new site-specific recombinase, named Dre and mice using C57Bl/6 ES cells with Flpo, a codon optimized version of the Flp-recombinase. Further we established methods for BAC transgenesis and gene targeting in human embryonic stem cells.

2) Conditional immortalization as a system for expansion of rare cell types. The system is based on tetracycline regulated expression of SV40 Large T Antigen and enables the isolation of adult cell types for conditional expansion. We performed cellular cloning of mesenchymal stomal cells isolated from tet-regulated Large T Antigen mice and identified polulations with distinct differentiation properties.

3) Identification of the molecular mechanisms involved in somatic cell reprogramming. The aim is to elucidate the role of histone methyltransferases (HMTs) and histone demethylases (HDMs) in the efficiency of reprogramming. An assay for induced reprogramming from mouse NS cells using transposase-mediated delivery of the reprogramming factors has been established. For testing the effect of the HMTs or HDMs we use tetracycline regulated overexpression or conditional mutagenesis.

Future prospects and goals

Correction of patient specific induced pluripotent stem cells by gene targeting
Dissect the role of histone demethylases in cellular reprogramming
Conditional immortalization for analyzing the lineage commitment of conditioanlly immortalized mesenchymal stromal cells

Selected publications

Andreu-Vieyra CV, Chen R, Agno J, Glaser S, Anastassiadis K, Stewart AF and Matzuk MM (2010): Mll2 is required in oocytes for bulk histone 3 lysine 4 trimethylation and global transcriptional silencing. PLoS Biology. 8(8): e1000453

Kranz A, Fu J, Duerschke K, Weidlich S, Naumann R, Stewart AF, Anastassiadis K. (2010): An improved Flp deleter mouse in C57Bl/6 based on Flpo recombinase. Genesis. 48(8): 512-20

Anastassiadis K, Rostovskaya M, Lubitz S, Weidlich S, Stewart AF. (2010): Precise conditional immortalization of mouse cells using tetracycline-regulated SV40 large T-antigen. Genesis. 48(4): 220-32

Anastassiadis K, Fu J, Patsch C, Hu S, Weidlich S, Duerschke K, Buchholz F, Edenhofer F, Stewart AF. (2009): Dre recombinase, like Cre, is a highly efficient site-specific recombinase in E. coli, mammalian cells and mice. Dis Model Mech. 2(9-10): 508-515

Cambridge SB, Geissler D, Calegari F, Anastassiadis K, Hasan MT, Stewart AF, Huttner WB, Hagen V, Bonhoeffer T. (2009): Doxycycline-dependent photoactivated gene expression in eukaryotic systems. Nat Methods. 6(7): 527-31

Lubitz, S., S. Glaser, J. Schaft, A.F. Stewart, K. Anastassiadis (2007): Increased apoptosis and skewed differentiation in mouse embryonic stem cells lacking the histone methyltransferase Mll2. Mol Biol Cell. 18(6):2356-66
 Konstantinos Anastassiadis
Konstantinos Anastassiadis

1993: Dr. sc.agr., TU Berlin

1993-1995: Post Doctoral work at the TU Munich

1996-2001: Post Doctoral work at the EMBL Heidelberg

2002-2003: Post Doctoral work at the BIOTEC/TU Dresden

2004-2006: Group leader, BIOTEC/TU Dresden

since Feb 2006: Group leader, CRTD