D30: Jürgen Behrens | Dominic Bernkopf, Department of
Experimental Medicine II
Axin at microtubuli
Axin is a key negative regulator of the oncogenic Wnt/beta-catenin pathway scaffolding the beta-catenin destruction complex. We suggest that the newly found anchoring of axin to microtubules (MTs) is of functional importance for regulating the pathway. We will (i) describe the dynamics of axin association with MTs; (ii) determine the biochemical basis of this interaction and its regulation by phosphorylation; and (iii) define the functional role of axin anchoring to MTs in Wnt signaling.
Prof. Dr. Jürgen Behrens
Phone: +49 9131 85-29109
Dr. Dominic Bernkopf
Phone: +49 9131 85-29122
D31: Anja Bosserhoff, Institute of Biochemistry
Modulation of oncogene-induced senescence
Oncogene-induced senescence (OIS) was recently introduced as a strong tumor suppressive mechanism seen e.g. in development of nevi out of melanocytes after BRAF mutation. Tumor cells like melanoma obviously can overcome these limiting mechanisms by further changes, however the molecular mechanisms leading to and overcoming OIS are just being started to be understood. We aim to understand the role of cell adhesion processes and mechanotransduction in induction and overcoming OIS.
Prof. Dr. Anja Bosserhoff
Phone: +499131 85-24190
D32: Peter Dietrich, Department of Medicine 1
NPY in chemo-resistance and immune-escape in HCC
Term: 01.03.2020 – 28.02.2023
Neuropeptide Y (NPY) and its receptors represent a highly conserved system which is involved in cancer-related hallmarks. However, the impact of the NPY-system on hepatocellular carcinoma (HCC) remains unclear. The aims of this study are i) to unravel the role of NPY-receptor/NPY-crosstalk in resistance to tyrosine kinase inhibitors such as sorafenib and lenvatinib in HCC, and ii) to analyze the unknown role of the NPY-system as a potential major determinant of immune-escape in HCC.
Dr. Dr. Peter Dietrich
Phone: +49 9131 85-45221
D33: Markus Metzler, Department of Pediatrics |
Dimitrios Mougiakakos, Department of Medicine 5
Immunometabolism in CML
Term: 16.05.2020 – 30.06.2023
Despite the improvement through tyrosine kinase inhibitors (TKIs), treatment resistance, relapse and therapy-induced side effects are central problems of CML therapy. Our interdisciplinary project addresses the question whether and how TKIs alter CML cell metabolism and induce synthetic lethality in combination with compounds specifically targeting metabolic pathways. Our approach could help to improve efficacy and reduce side effects of CML treatment in pediatric and adult patients alike.
Prof. Dr. Markus Metzler
Phone: +49 9131 85-33117
Prof. Dr. Dimitrios Mougiakakos
D34: Andreas Ramming, Department of Medicine 3 |
Michael Stürzl, Department of Surgery
Fibroblast polarization in colorectal carcinoma
Term: 01.05.2020 – 31.07.2023
We have identified PU.1 as a key regulator of fibroblast polarization. Its role in colorectal carcinoma (CRC) is unknown. We will address the following aims: (1) characterization of cancer-associated fibroblast (CAF) heterogeneity in CRC, (2) analysis of CAF polarization-dependent fibrocrine effects in vitro and (3) in experimental animal models, and (4) validation of the results in CRC tissues. Deciphering the role of fibroblast polarization in CRC may provide a new target for therapy.
Dr. Andreas Ramming
Phone: +49 9131 85-34742
Prof. Dr. Michael Stürzl
Phone: +49 9131 85-39520
D35: Johannes Schödel, Department of Medicine 4
Interactions of DPF3 and hypoxia in renal cancer
Term: 01.07.2020 – 31.12.2022
The renal cancer risk SNP on chromosome 14q24.2 creates a novel Hypoxia inducible transcription factor (HIF)-binding DNA element in an intronic region of the DPF3 gene, a member of the SWI/SNF chromatin remodelling complex. DPF3 is upregulated in a SNP- and HIF-dependent fashion in renal tubular cells. We investigate the regulation of DPF3 in renal cells and cancer as well as its contribution to global chromatin status and transcription factor binding to critical DNA regions.
PD Dr. Johannes Schödel
Phone: +49 9131 85-39560
D36: Reiner Strick, Department of Obstetrics and Gynaecology |
Arndt Hartmann, Department of Pathology
Endogenous retroviruses drive tumor inflammation
Term: 01.03.2020 – 20.02.2023
This proposal will focus on the molecular basis of tumor inflammation of two different advanced cancers; Bladder cancer (MIBC) and Ovarian cancer (OVCA) with poor survival outcomes and high recurrence rates. Endogenous retrovirus (ERV) activations are linked with innate immunity and tumor inflammation. We will correlate patient immune signatures with ERVs and determine the functional role of ERVs, including dsRNA and RNA/DNA intermediates using tumors, cell lines and tumoroids of MIBC and OVCA.
Prof. Dr. Reiner Strick
Phone: +49 9131 85-36671
Prof. Dr. Arndt Hartmann
Phone: +49 9131 85-22286