Research Program A: Cell Biology and Tumor Biology

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Below you will find DKFZ divisions and research groups of the Research Program Cell Biology and Tumor Biology who are interested in recruiting Postdocs within the 2018 DKFZ Postdoctoral Fellowships Selection.

Please note that this is not an exhaustive list and new groups are continously added.

You may also contact the principal investigator of the DKFZ research group of your choice directly to discuss about current possibilities. More information about hiring labs can be found below and descriptions of DKFZ research programs via the general topic locator.

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Cell Signaling and Metabolism – Dr. Wilhelm Palm

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RESEARCH PROFILE

Nutrients supply the energetic and biosynthetic pathways which underlie all cellular functions. To match the metabolic demands of different physiological and pathological states, cells must tightly control nutrient uptake and utilization. For instance, quiescent cells import sufficient bioenergetic substrates to sustain homeostasis, but cells must increase nutrient uptake to grow and divide. To survive starvation, cells must access alternative nutrient sources. To grow unrestrainedly, cancer cells must acquire autonomous control over nutrient uptake.
We study nutrient acquisition and metabolism in mammalian cells. This problem is challenging, because mammalian cells are surrounded by diverse nutrients, which they import via multiple pathways. To understand how cells acquire nutrients, we characterize their cellular import pathways. Here, we are especially interested in metabolic roles of macropinocytosis and the lysosome. To understand how cells make choices between distinct nutrient acquisition strategies, we study their regulation by signal transduction. Here, we focus on growth factor signaling and the nutrient-sensing mTOR pathway. Cancer cells have increased metabolic demands, but must also cope with harsh metabolic environments. Hence, we study how oncogenes confer cancer cells metabolic autonomy to support uncontrolled growth and metabolic flexibility to navigate nutrient-poor tumor microenvironments. To this end, we combine imaging, mass spectrometry and CRISPR approaches and develop novel tissue culture systems that accurately model metabolic environments.

 

PROJECT TOPICS

We are looking for a highly motivated postdoctoral fellow who would like to address fundamental problems at the interface of metabolism, signaling and cell biology. Within this framework, there are a variety of projects available with focus on basic or cancer biology, depending on personal interests.

Please visit our website for further information on our research and recent publications.

 

LINK: https://www.dkfz.de/en/signaltransduktion-und-stoffwechsel-der-zelle/index.php

 

Neuronal Signaling and Morphogenesis – Dr. Annarita Patrizi

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RESEARCH PROFILE AND PROJECT TOPICS

Our young and dynamic team is looking for an enthusiastic and outstanding postdoctoral fellow to build a new research group dedicated to the identification of instructive signals critical for normal and pathological brain development. In particular we aim to unravel intrinsic and extrinsic factors essential for development and refinement of cortical brain circuit. To this end we will focus on the role of the choroid plexus, an unique interface between blood and cerebrospinal fluid. With the help on a multidisciplinary approach, including transcriptomic, proteomic, molecular and bioinformatic methods we plan to identify and to analyze unbiased choroid plexus - cerebrospinal fluid instructive signals during normal development and in neoplasm models. The postdoctoral fellow will establish a new pipeline for molecular and biochemical identification of unbiased instructive signals from mice to humans and perform meta analysis of multi-omics experiments.
We plan on using a wide spectrum of methods and offer a supportive, team-spirited, working environment in excellent facilities. The ideal candidate should possess a solid research background in at least one of the following areas: cellular and developmental neuroscience, single cell sequencing techniques, proteomics, bioinformatics and cell and organoid cultures. For this position the applicant must have the ability to independently drive a project forward, to work both independently and as part of a team, to enjoy working in multidisciplinary environments. Excellent communication skills and problem-solving skills are also required.

 

LINK: https://www.dkfz.de/en/neuronale-signalwege-morphogenese

Redox Regulation – PD Dr. Tobias P. Dick

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RESEARCH PROFILE

Our research is organized in three consecutive steps: (1) We aim to understand the detailed molecular mechanisms by which redox signals are transmitted inside cells. (2) We make use of mechanistic insights to create tools that enable monitoring and manipulating redox signals inside living cells and model organisms. (3) We employ these tools to obtain more detailed understanding of redox homeostasis in either healthy or malignant situations. We are interested in intervention strategies that enhance cytoprotective signals in healthy cells and disrupt them in malignant cells.

 

LINK

http://www.dkfz.de/en/redoxregulation/index.php

Vascular Oncology and Metastasis – Prof. Dr. Hellmut Augustin

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RESEARCH PROFILE

Jointly affiliated with the DKFZ (www.augustinlab.de) and the European Center for Angioscience (www.angioscience.de), our laboratory studies the cellular crosstalk in the tumor microenvironment. We thereby bridge vascular biology and oncology, to focus on disease mechanisms most importantly contributing to human mortality.

Directed by the recently funded ERC advanced grant 'AngioMature', the study of vessel maturation mechanisms and acquisition of organotypic differentiation during development, adult homeostasis and aging is increasingly emerging as center stage research field (see: Augustin and Koh, Science, 2017 for recent review). This is simply due to the fact that loss of the quiescent vascular phenotype is at the heart of vascular dysfunction, which is a leading contributor to at least 70% of human mortality (notably cardiovascular failure and cancer). The recent advances in big data omics analysis (up to single cell level) are presently revolutionizing vascular biology research and we pursue several projects along these lines (see Schlereth et al., eLife, 2018)

In oncology, we have a strong focus on preclinical tumor model development in order to address key unanswered questions related to tumor progression and metastasis (see Gengenbacher et al., Nat Rev Cancer, 2017 for recent review). We apply such models for the mechanistic validation of novel candidate molecules functionally controlling the premetastatic and metastatic niches.

PROJECT TOPICS

We presently consider the applications of highly motivated postdoctoral candidates with a genuine interest in vascular and/ or tumor biology research. Experience in either field or contribution of specialized knowhow would be a major asset, but is not mandatory.

Please visit our website for further information on our research and recent publications.

LINK: www.augustinlab.de

Molecular Neurobiology – Prof. Dr. Ana Martin-Villalba

Multi-omics studies of neural stem cells

Multi-omics studies of neural stem cells
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RESEARCH PROFILE

Over a million of different cell types and billions of connections underlie brain function. In the embryonic brain glial progenitors are responsible to generate the cellular diversity, however in the adult brain progenitor competences becomes more restricted. Our group has demonstrated, that an ischemic injury activates dormant glial progenitors by inducing an inflammatory transcriptional signature and demethylation of developmental enhancers in these glial progenitors.
The overall goal of this project is to identify ways to efficiently activate enhancers in dormant glial progenitors to re-direct lineage choices towards re-establishing brain function following injury. Technologies including clonal lineage tracing, genome editing, and single cells omics combined with genetic and injury animal models will be applied aiming at an integrated manipulation of the epigenome, transcriptome and environment for directed brain repair through endogenous progenitors.
This multidisciplinary approach combines cutting edge technologies in functional genomics, developmental biology and translational research.

Methods that will be used: A wide variety of state-of-the-art molecular, genetic, biochemical and cell biological technologies, including stem cell methodologies, single cell sequencing, RNA-Sequencing, Methylome, genome editing and work in a physiologically relevant mouse model of human brain damage.

Personal qualifications:
• PhD in biology, molecular medicine or any related discipline
• Extended knowledge in brain development or CrisprCas-directed genome editing
• Practical expertise in next generation sequencing
• High motivation for team work and for collaborative projects

 

LINK

http://www.dkfz.de/en/neurobiologie-von-gehirntumoren/index.php

Cell Fate Engineering and Disease Modeling – Dr. Moritz Mall

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RESEARCH PROFILE

Cancer is one of the leading causes of morbidity and mortality worldwide with brain tumors (gliomas) such as medulloblastoma and glioblastoma multiforme affecting both children and adults. Despite much progress in identifying oncogenes and tumor suppressors involved in glioma formation and progression, clinical outcomes of glioma treatment remain extremely poor. More recent avenues in glioma research and in other cancers have established dedifferentiation and adoption of stem cell-like properties as a hallmark of cancer. Our previous work showed that transcriptional repression drives neuronal differentiation and inhibits several brain tumor-promoting pathways such as Wnt, Notch, and Hedgehog (Mall, Nature 2017). This suggests that active transcriptional repression might act as a tumor suppressor itself and opens the exciting possibility that loss of neuronal identity could cause brain cancer.

PROJECT TOPICS

The postdoc project will investigate how transcriptional repression can counteract tumorigenesis in gliomas and if impaired neuronal differentiation or dedifferentiated neurons can lead to cancer formation.

 

CONTACT

Please contact Dr. Moritz Mall directly for further information: m.mall@dkfz.de

 

Stem Cells and Cancer – Prof. Andreas Trumpp

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RESEARCH PROFILE and PROJECT TOPICS

Genetic alterations of stem cells can lead to the generation of "cancer stem cells" (CSCs) that drive tumorigenesis and metastasis. Starting with mouse models, we extend our work to the analysis of primary patient samples using numerous genomic and mechanistic approaches including single cell assays and link the results to clinical parameters with the goal to develop innovative strategies to detect and target cancer and metastatic stem cells and break therapy resistance.

Our recent work identified critical roles for the Vitamin A-Retinoic acid signaling and the MYC oncogene in stem cell identity and dormancy (Scognamiglio et al., 2016 Cell; Cabezas-Wallscheid et al., 2017 Cell). We characterized and dissected a modular super enhancer, which is responsible for controlling the precise expression levels of Myc along the entire hematopoietic stem cell hierarchy (Bahr et al., 2018 Nature). Furthermore, we have used single-cell technologies to determine the structure and molecular landscape of the human hematopoietic system (Velten et al., 2017 Nature Cell Biology). In leukemic stem cells, we have identified the enzyme BCAT1 as an alternative pathway to mutations in IDH and TET2 leading to DNA hypermethylation and therapy resistance (Raffel et al., 2017 Nature). Next to our work on circulating tumor cells in breast cancer, we uncovered in pancreatic cancer a novel resistance mechanism based on CYP3A5 expression, for which we are now developing novel combination therapies and are planning a clinical trial (Noll et al., 2016 Nature Medicine).

The Trumpp lab offers an interdisciplinary and international environment and is part of the Heidelberg Institute for Stem Cell Technology and Experimental Medicine – HI-STEM.

 

LINK: https://www.dkfz.de/en/stammzellen-und-krebs

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