Visual Universitätsmedizin Mainz

Current Projects

Project 1: The importance of Cohesin activity at active cis-regulatory regions during the normal hematopoiesis and leukemogenesis – cooperation with Professor Brian Huntly, University of Cambridge, UK

Myeloid malignancies are heterogeneous neoplasia that share many common characteristics, such as altered transcriptional regulation caused by recurrent mutations of signaling, transcription and epigenetic factors. Several of these mutations occur in members of the Cohesin complex (STAG2, RAD21, SMC1a or SMC3, less frequent STAG1). The mutations are mutually exclusive, are predicted to cause loss of function alleles and a decrease of complex activity. In this study we aim to determine a mechanism for the establishment of cohesin-deficient myeloid neoplasia utilizing integrative analysis of cohesin binding, gene expression, chromatin state and 3D-DNA topology at genome scale, assessing different cellular states - hematopoietic progenitors, erythroid and myeloid cells - followed by matched analysis after inducible shRNA-mediated knockdown (KD) of multiple cohesin members. We additionally aim to translate our results into pre-established in-vitro and in-vivo models of leukemogenesis, finally intending to exploit therapeutic targets that Cohesin-mutated myeloid neoplasia rely on.

Project 2: Targeting aberrant NCAM1 expression in Acute Myeloid Leukemia – cooperation with PD Dr. Thomas Kindler, University Medical Center Mainz

Acute myeloid leukemia (AML) is a heterogeneous disease of the hematopoietic progenitor cell driven by the subsequent acquisition of genetic alterations. Approximately 20% of AML patients display strong expression of NCAM1 (neural cell adhesion molecule 1;  CD56). Expression of NCAM1 is associated with poor overall survival; however, the functional role of aberrant NCAM expression has not been investigated to date. The goal of this study is to examine the biological role of NCAM in AML and to explore whether NCAM represents a potential therapeutic target.