More information

Alexander Wurm Group

The interplay between non-coding RNAs and the epigenome – a map for precision oncology?

Portrait Alexander Wurm

Cancer comprises a group of lethal diseases caused by malignant transformation of healthy cells. Biologically, cancer is a very heterogeneous collection of different neoplasias that share distinct features: Increased cellular survival combined with an increased proliferation and a reduced differentiation ability. The molecular origin of this phenotypic phenomenon shows huge variations that have only partially been understood.

Recent studies revealed that different tumor entities share molecular characteristics that influence intracellular pathway activity and treatment response. Hence, novel therapy concepts are needed that consider the molecular properties of every individual tumor and every individual patient. Therefore, various biomarkers based on gene mutations, chromosomal translocations or single gene expression levels are under consideration. However, including gene expression analysis into clinical routine diagnostic is challenging. Major pitfalls encompass low mRNA-protein correlation and the lack of appropriate controls.

Non-coding RNAs (ncRNAs) are functional RNA molecules that are transcribed from DNA but not translated into proteins. Considering that only around 2% of the human transcriptome is translated, ncRNAs represent a huge proportion of the DNA encoded genetic information. Many ncRNA subspecies have been described, for instance microRNAs, small nucleolar RNAs or long non-coding RNAs (lncRNAs). They play pivotal roles in a plethora of cellular processes in development and diseases, including cancer, and can interact with nearly all cellular components.

By exploring various cancer entities and state-of-the art techniques, we want to demonstrate that non-coding RNAs can drive tumorigenesis and influence anti-cancer treatment response. In addition, we will explore their suitability to function as biomarkers for precision oncology based approaches.

We are currently focusing on the following aspects:

MiRNA signatures as tool for precision oncology

MicroRNAs (miRNAs) are small non-coding RNAs that influence many biological processes including cancer initiation and progression. Expression of several miRNAs is associated with treatment response to standard first line therapy in cancer. In comparison to protein coding genes, measurement of miRNA signatures by high throughput RNA sequencing technologies give more consistent information about possible cellular activities as they are determined at a mature stage. Thus, we monitor the potential to use these signatures as biomarkers for pathway activities and subsequent target therapies in cancer.

Non-coding RNAs and leukemia initiating cells in AML

Acute myeloid leukemia (AML) is a disorder of the hematopoietic system caused by malignant alterations of the myeloid differentiation cascade. AML is a heterogeneous disease that consists of highly proliferative blast cells and a smaller population of stem cell-like cells, the leukemia initiating cells (LICs). The LICs show distinct epigenetic and non-coding RNA signatures. We are interested how these signatures contribute to leukemia initiating, progression and treatment response.

lncRNA-epigenome landscapes in gastrointestinal cancers

Similar molecular mechanisms can be found in solid tumors. Hence, we are interested how lncRNAs can shape the epigenome of colorectal cancers and how this knowledge can give novel options for target epigenetic therapies

Future Projects and Goals

  • Identification and characterization of cancer-driving ncRNAs
  • Characterization of ncRNA-epigenome landscapes in various cancers
  • Defining prognostic ncRNA scores for different targeted cancer therapies
  • Exploring therapy resistance associated ncRNAs

Methodological and Technical Expertise

  • RNA interaction assays (such as RIP)
  • Functional Genomics for ncRNAs and protein coding genes (CRISPR-Cas9, shRNA)
  • Various in vitro and in vivo leukemia models
  • Various models for cancer drug resistance
  • ncRNA gene expression pipelines (PCR, NGS)

Apply now!

Alexander Wurm is recruiting in the PhD Fall Selection 2021

Apply now!
Open Project
  • Understanding the epigenome-lncRNA network in cancer progression and response to epigenetic therapies
    Preferred Course of Study/Expertise of Candidate: Biomedicine, Cell Biology, Molecular Biology

CV

Since December 2020
DKTK investigator

Since July 2020
MSNZ Group Leader at NCT Dresden

2019–2020
Postdoc, NCT Dresden

2017–2018
Postdoc, Leipzig University Hospital

2013–2017
PhD student, Leipzig University and Institute of Molecular Genetics, Prague

2011–2013
Research Associate, Leipzig University Hospital

2005–2010
Diploma (MSc equivalent) in Biology, TUD

Selected Publications

Wurm AA, Pina C
Long Non-coding RNAs as Functional and Structural Chromatin Modulators in Acute Myeloid Leukemia.
Front Oncol. 9:899 (2019)

Krakowski RHE*, Wurm AA*, Gerloff D, Katzerke C, Bräuer-Hartmann D, Hartmann J, Wilke F, Thiede C, Müller-Tidow C, Niederwieser D, Behre G
MiR-451a abrogates treatment resistance in FLT3-ITD-positive acute myeloid leukemia.
Blood Cancer J. 8(3):36 (2018)
*both authors contributed equally

Wurm AA, Zjablovskaja P, Kardosova M, Gerloff D, Bräuer-Hartmann D, Katzerke C, Hartmann JU, Benoukraf T, Fricke S, Hilger N, Müller AM, Bill M, Schwind S, Tenen DG, Niederwieser D, Alberich-Jorda M, Behre G
Disruption of the C/EBPα-miR-182 balance impairs granulocytic differentiation.
Nat Commun 8(1):46 (2017)

Zjablovskaja P, Kardosova M, Danek P, Angelisova P, Benoukraf T, Wurm AA, Kalina T, Sian S, Balastik M, Delwel R, Brdicka T, Tenen DG, Behre G, Fiore F, Malissen B, Horejsi V, Alberich-Jorda M
EVI2B is a C/EBPα target gene required for granulocytic differentiation and functionality of hematopoietic progenitors.
Cell Death Differ. 24(4):705–716 (2017)

Wurm AA, Tenen DG, Behre G
The Janus-faced Nature of miR-22 in Hematopoiesis: Is It an Oncogenic Tumor Suppressor or Rather a Tumor-Suppressive Oncogene?
PLoS Genet 13(1):e1006505 (2017)