05-06 November 2015 Naturfreundehaus Bruchsal PostDoc Retreat

2015
PostDoc Retreat
Bruchsal
05-06 November 2015
Naturfreundehaus Bruchsal
PDN
presents
Dear PostDocs,
We are welcoming you to the 4th PostDoc Retreat! These retreats were initiated to give the
broad spectrum of DKFZ PostDocs a forum to interact, network and present their recent
advancements in cutting edge research.
We are looking forward to going with you through a very exciting scientific and social program.
Besides the scientific presentations we would like to address special issues that every PostDoc
has to face, we are pleased to welcome our guest speakers Susan Kentner and Aidan Budd.
They will present their ideas and suggestions for funding/grant applications and networking,
respectively. Furthermore, we are aiming to activate a lively conversation during our panel
discussion giving you the chance to point out aspects and ideas you would like to emphasize.
We, the PostDoc Network (PDN), hope
you enjoy the Retreat.
The scientific and personal diversity of
the postdoctoral community encountered
at the DKFZ required the establishment
of a unifying platform that efficiently
represents the interests and need of
postdocs. The PDN is continually aiming
to maintain and grow a vibrant
postdoctoral experience at the DKFZ.
Several
subgroups
have
been
established to provide the optimal
infrastructure to achieve our goals:
Visibility
Career Perspectives
Networking
The PDN Committee is meeting on a regular basis every second Thursday at 11.00am. You
could get many personal benefits out of an active participation in the life of the PDN, so don’t
hesitate to bring in your own ideas, to contact us at pdn@dkfz.de and to join us!
The PDN wishes you a successful Retreat and hope to see you at the up-coming PDN events.
Best Regards,
The PDN Retreat Organizing Team
Kristin Rattay
Marina Laplana
Antje Reuter
Heiko Weyd
Ann-Christin Gaupel
Sreejith Rajasekharan
Eva Nievergall
Yi Sun
Table of Contents
Program………………………………………………..................
7
Guest Speakers’ Portraits………………………………………..
10
Oral Presentations Overview…………………………………….
12
Oral Presentations………………………………………………..
13
Poster Presentations Overview………………………………….
24
Poster Presentations……………………………………………..
26
Matched Expertise Exchange…………………………………….
47
List of Participants…………………………………………………
49
Program
November 5th, Thursday
10:00
Registration
10:15
Welcome
11:00
Oral presentations - Session 1
12:30
Lunch
14:00
Guest Speaker - Dr. Aidan Budd
15:15
Coffee break / Poster session 1
16:15
Oral presentations - Session 2
17:15
Round Table Discussion
19:00
Dinner
20:30
Evening program
November 6th, Friday
08:00
Breakfast
09:00
Oral presentations - Session 3
10:20
Coffee break / Poster session 2
11:15
Guest Speaker - Dr. Susan Kentner
12:30
Lunch
13:30
Matched Expertise Exchange
14:30
Coffee break / Poster session 3
15:30
Closing remarks, prize ceremony and departure
GUEST SPEAKERS’
PORTRAITS
PostDoc Retreat 2015
Dr. Budd, Aidan
Dr. Aidan Budd is a senior project manager for bioinformatics at the European
Molecular Biology Laboratory (EMBL) in Heidelberg. He obtained his PhD in
Bioinformatics at EMBL Heidelberg, worked as a commissioning editor at Wiley-VCH
and as a computational biologist at EMBL afterwards.
A key element of Aidan’s work involves organizing and facilitating scientific events,
including courses, conference sessions, and unconferences/unseminars e.g. the
Heidelberg Unseminars in Bioinformatics (HUB http://hub-hub.de). Another focus of his
work is on facilitating collaborations, networking, and community building amongst
scientists.
10
PostDoc Retreat 2015
Dr. Kentner, Susan
Dr. Susan Kentner is in the DKFZ department “Administrative Project Management”,
with special responsibility for EU and international funding programs. After 20 years’
experience in medical and scientific publishing, including stints with Springer-Verlag in
Heidelberg, VCH-Wiley in Weinheim and 12 years as managing director of her own
medical publishing company Palatium Verlag, she joined the Helmholtz Association in
2002 as the Scientific Officer for health research in Brussels, and became head of the
Helmholtz Brussels Office, where she worked until June 2014. Susan also has a record
as a successful trainer in communication skills and has taught workshops and lectured
on subjects relating to grant writing, research management in health and life sciences,
EU affairs and collaboration opportunities.
11
PostDoc Retreat 2015
Oral Presentations
Overview
Session
Session 1
Thursday
05.11.2015
11:00-12:30
Session 2
Thursday
05.11.2015
16:15-17:15
Session 3
Friday
06.11.2015
9:00-10:20
Talk
First Name
T1.1
Heiko
Weyd
The tolerogenic function of annexins on
apoptotic cells is mediated by the
annexin core domain
T1.2
Yan
Tang
In vivo recording of hypothalamic
neurons controlling feeding behavior:
Transition from Shanghai to Heidelberg
Title
T1.3
Hua
Jing
Imaging and selective elimination of
glioblastoma stem cells with theranostic
near-infrared-labeled CD133-specific
antibodies
T1.4
Mikolaj
Slabicki
Systematic dissection of CD20
regulation in lymphoma
T2.5
Roberta
Scognamiglio
Loss of Myc Activity Induces Cellular
Dormancy in Embryonic Stem Cells
Mimicking the Status of Diapause
Embryos
T2.6
Abhishek
Kumar
Oncogenomics of familial colorectal
cancer for identification of germline
variants with deleterious implications
T2.7
Mona
Malz
Academic drug discovery at the DKFZ
T3.8
Christian
Breunig
Regulation of the oncoprotein c-Met in
breast cancer and its effect on cell
migration
T3.9
Michael
Fletcher
de novo transcriptome assembly finds
novel glioblastoma subtype-specific
transcripts
T3.10 Konstantina Rowald
T3.11 Petros
12
Last Name
Selective advantages gained through
chromosome instability outweigh fitness
drop during cancer initiation
A novel thymoma-associated
Christopoulos immunodeficiency with increased naive
T cells and reduced CD247 expression
PostDoc Retreat 2015
T1.1 - Weyd, Heiko
The tolerogenic function of annexins on apoptotic cells is mediated by the
annexin core domain
Björn Linke1, Lucie Abeler-Dörner1,2, Veronika Jahndel1, Alexandra Kurz1, Andrea
Mahr1,2, Sandra Pfrang1, Linda Linke1,4, Peter H. Krammer1, Heiko Weyd1
1
Division of Immunogenetics, Tumor Immunology Program, German Cancer Research
Center, 69120 Heidelberg, Germany.
2
Current affiliation: Peter Gorer Department of Immunobiology, London, SE1 9RT,
United Kingdom.
3
Current affiliation: Immatics Biotechnologies GmbH, 72076 Tübingen, Germany.
4
Current affiliation: Division of Pediatric Neurooncology, German Cancer Research
Center, 69120 Heidelberg, Germany.
Immunological tolerance is constantly being maintained in the periphery by dendritic
cells (DCs) processing material from apoptotic cells (ACs) in the steady-state. While
research has focussed on the uptake of ACs by phagocytes, tolerogenic signals
exposed by the ACs are much less well defined. In this article, we show that the
annexin (Anx) family members AnxA5 and AnxA13 translocate to the surface of ACs to
function as redundant tolerogenic signals in vitro and in vivo. Exposure of bone marrowderived dendritic cells (BMDCs) to AnxA5 or AnxA13 in vitro resulted in the inhibition of
both the pro-inflammatory cytokine secretion and the upregulation of co-stimulatory
molecules upon TLR-stimulation. The highly conserved annexin core domain was
sufficient to mediate these effects, whereas recognition by N-formyl peptide receptor
(FPR) family members was dispensable. In vivo, co-injection of apoptotic OVAexpressing and Anx-expressing cells prevented induction of antigen-specific CD8+ T
cells. These results suggest that several annexins contribute to AC-induced
immunosuppression of DC activation. Manipulating Anx-mediated immunosuppression
may, therefore, prove beneficial for patients with cancer or autoimmune diseases and
chronic inflammatory disorders.
13
PostDoc Retreat 2015
T1.2 - Tang, Yan
In vivo recording of hypothalamic neurons controlling feeding behavior:
Transition from Shanghai to Heidelberg
Yan Tang1, Long-Nian Lin1, Valery Grinevich1,2
1
Key Laboratory of Brain Functional Genomics of Ministry of Education, School of Life
Sciences, East China Normal University, Shanghai 200062, China.
2
Schaller Research Group on Neuropeptides, German Cancer Research Center DKFZ
and Network Cluster of Excellence of the University of Heidelberg, Heidelberg 69120,
Germany.
The hypothalamus is the key brain center regulating energy homeostasis. Thus it
becomes a hotspot to study feeding behavior, which is profoundly influence by energy
balance. During the last decade it was shown that several hypothalamic structures such
as paraventricular (PVN), arcuate, ventromedial nuclei, as well as the lateral
hypothalamus contribute to the control of appetite. However – despite many studies
focused on molecular mechanisms of hypothalamic obesity (see, for example, Vinnikov
et al., J. Neurosci., 2014), the electrical activity of neurons of these areas in the context
of feeding behavior was not explored. Therefore, the team of co-authors from Shanghai
used in vivo multi-electrodes recording system to monitor activity of hypothalamic
neurons during starvation and eating behaviours. In the course of these studies three
types of hypothalamic neurons were identified, which have been activated during (type
1) and food intake silent neurons (type 2). However, the main obstacle for the
interpretation of these results was the lack of identification of their nature. Therefore we
initiated cooperation to establish optoelectrode-based recordings of specific neuronal
populations. Our first choice is the population of PVN neurons expressing oxytocin,
which is one of most powerful anorexic peptides. In these studies we will combine
experiences in the in vivo electrophysiology (Yan Tang), optogenetics and viral vector
(Valery Grinevich’s group) to record specific types of hypothalamic neurons during
starvation and eating as well as other forms of feeding-related social behaviours. This
project is highly relevant to the modern human society, which is severely suffered by
overeating, low energy expenditure and obesity.
14
PostDoc Retreat 2015
T1.3 - Jing, Hua
Imaging and selective elimination of glioblastoma stem cells with theranostic
near-infrared-labeled CD133-specific antibodies
Hua Jing1,3, Claudia Weidensteiner2, Wilfried Reichardt2, Xuekai Zhu1,3, Hisataka
Kobayashi4, Gabriele Niedermann1,3
1
Dept. for Radiation Oncology University Hospital Freiburg, D-79106 Freiburg,
Germany.
2
Radiology Medical Physics, University Hospital Freiburg, D-79106 Freiburg, Germany.
3
German Cancer Consortium (DKTK), Freiburg, and German Cancer Research Centre
(DKFZ), D-69121 Heidelberg, Germany.
4
Molecular Imaging Program, Center for Cancer Research, National Cancer Institute,
National Institutes of Health, Bethesda, MD 20892, USA.
Near-infrared photoimmunotherapy (NIR-PIT), which employs monoclonal antibody
(mAb)-phototoxic phthalocyanine dye IR700 conjugates, permits the specific, imageguided and spatiotemporally controlled elimination of tumor cells. Here, we report the
highly efficient NIR-PIT of human tumor xenografts initiated from patient-derived cancer
stem cells (CSCs). Using glioblastoma stem cells (GBM-SCs) expressing the prototypic
CSC marker AC133/CD133, we also demonstrate here for the first time that NIR-PIT is
highly effective against brain tumors. The intravenously injected theranostic AC133 mAb
conjugate enabled the non-invasive detection of orthotopic gliomas by NIR fluorescence
imaging, and reached AC133+ GBM-SCs at the invasive tumor front. AC133-targeted
NIR-PIT induced the rapid cell death of AC133+ GBM-SCs and thereby strong
shrinkage of both subcutaneous and invasively growing brain tumors harbouring
AC133+ GBM-SCs. A single round of NIR-PIT extended the overall survival of mice with
established orthotopic gliomas by more than a factor of two, even though the harmless
NIR light was applied through the intact skull. Humanised versions of this theranostic
agent may facilitate intraoperative imaging and histopathological evaluation of tumor
borders and enable the highly specific and efficient eradication of CSCs.
15
PostDoc Retreat 2015
T1.4 - Slabicki, Mikolaj
Systematic dissection of CD20 regulation in lymphoma
Mikołaj Słabicki, Thorsten Zenz
Department of Translational Oncology, National Center for Tumor Diseases (NCT) and
German Cancer Research Center (DKFZ), Heidelberg, Germany.
Despite the successful use of CD20 antibodies targeting B-cell lymphoma (e.g.
rituximab), the mechanisms underlying regulating of CD20 (encoded by MS4A1) are far
from clear. We aimed to understand the regulatory networks controlling CD20
expression. Employing bioinformatics analysis of MS4A1 promotor region allowed us to
describe features of MS4A1 promoter region including a set of transcription factors
directly binding in the regulatory region. To identify novel regulators of CD20, we used a
FACS-based (positive selection) shRNA screen in a Burkitt’s lymphoma model. We
report 91 potential regulators including several known CD20 regulators (SPI1, STAT5A,
PAX5), which scored in the screen. In addition, we report novel repressors of CD20
including CREM (cAMP Responsive Element Modulator). ChIP-PCR confirmed that
CREM binds upstream of MS4A1, suggesting direct repression of MS4A1. We
characterize Chromodomain Helicase DNA Binding Protein 4 (CHD4) and Methyl-CpG
Binding Domain Protein 2 (MBD2), two Nucleosome Remodeling Deacetylase (NuRD)
complex members, as positive regulators of CD20. In summary, we provide a global
view on the regulatome of CD20 and employing FACS-based RNAi approach allowed
identifying novel repressor (CREM) and activators (CHD4 and MBD2) of CD20
expression in a lymphoma model.
16
PostDoc Retreat 2015
T2.5 - Scognamiglio, Roberta
Loss of Myc Activity Induces Cellular Dormancy in Embryonic Stem Cells
Mimicking the Status of Diapause Embryos
Roberta Scognamiglio1,2, Nina Cabezas-Wallscheid1,2, Marc-Christian Thier1,2, Sandro
Altamura3, Daniel Baumgärtner1,2, Alejandro Reyes4, Larissa Carnevalli1,2, Aine
Prendergast1,2, Lisa von Paleske1,2, Thorsten Boroviak5, Philipp Wörsdörfer6, Robert N.
Eisenman7, Frank Edenhofer6, Paul Bertone4,5, Wolfgang Huber4, Franciscus van der
Hoeven8, Austin Smith5 and Andreas Trumpp1,2,9
1
Division ofStem Cells and Cancer, DeutschesKrebsforschungszentrum (DKFZ), Heidelberg,
Germany.
2
Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH,
Heidelberg, Germany.
3
Department of PediatricHematology, Oncology and Immunology, University of Heidelberg,
Heidelberg, Germany.
4
Genome Biology Unit, European Molecular Biology Laboratory (EMBL), Heidelberg, Germany.
5
Welcome Trust-Medical Research Council Stem Cell Institute & Department of Biochemistry,
University of Cambridge, Tennis Court Road, Cambridge CB2 1QR, UK.
6
Stem Cell and Regenerative Medicine Group, Institute of Anatomy and Cell Biology, JuliusMaxi i i
- i e i
g
g e
7
Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington
98109, USA.
8
Transgenic Service, DeutschesKrebsforschungszentrum (DKFZ), Heidelberg, Germany.
9
German Cancer Consortium (DKTK), Heidelberg, Germany.
Mouse embryonic stem cells (ESCs) can be maintained in a naïve state of pluripotency by
culture in the presence of LIF as well as MAPK and GSK3b inhibitors (2i). To genetically
address the role of c-Myc and N-Myc in naïve ESCs, both genes were deleted by using Cremediated recombination. Myc double knockout (dKO) cells stop proliferating without signs of
apoptosis. Upon deletion, dKO ESCs form small, undifferentiated colonies maintaining the
expression of Oct4, Nanog and Sox2. Whole transcriptome analysis (RNA-seq) confirmed the
expression of the core pluripotency network in dKO ESCs, but revealed down-regulation of most
metabolic and biosynthetic aspects of cellular physiology, as cell cycle activity, DNA replication,
ribosomal biogenesis and DNA/protein synthesis. The cellular and molecular phenotype of MycdKO ESC i co i e wi h
of “ io
he ic do
c ” S iki g we fi d h
he
signature of dKO ESCs is remarkably similar to the expression signature of diapauses arrested
pre-implantation embryos. In mice, reversible diapause of early embryos is observed in mothers
still feeding a litter, as a strategy to improve the reproductive fitness. Very low expression of
networks such as DNA synthesis, cell division, metabolic activity is observed in both diapause
embryos and Myc-dKO ESCs. In summary, we show that in the context of naïve ESCs Myc is a
master regulator of cellular biosynthesis. During the self-renewal process Myc controls cellular
proliferation while the maintenance of stem cell fate is independent on Myc activity. Moreover,
our data raise the possibility that Myc activity controls the reversible arrest of diapause embryos.
17
PostDoc Retreat 2015
T2.6 - Kumar, Abhishek
Oncogenomics of familial colorectal cancer for identification of germline variants
with deleterious implications
Abhishek Kumar1,*, Asta Försti1,*, Nagarajan Paramasivam2,3, Matthias Schlesner2,
Dagmara Dymerska4, Jan Lubiński4 and Kari Hemminki1,*
1
Molecular Genetic Epidemiology, Deutsches Krebsforschungszentrum (DKFZ),
Heidelberg, Germany
2
Division of Theoretical Bioinformatics (B080), German Cancer Research Center
(DKFZ), Heidelberg, Germany
3
Medical Faculty of Heidelberg, Heidelberg University, Germany
4
Department of Genetics and Pathology, International Hereditary Cancer Center,
Pomeranian Medical University,
Szczecin, Poland
*
Correspondence: AK - a.kumar@dkfz.de, AF - A.Foersti@dkfz.de KH –
K.Hemminki@dkfz.de
Oncogenomics has made huge progress since availability of human genome with rapid
advancements in the high-throughput technologies. Currently, it has become the
standard method for deciphering the genetic basis of human cancer and several studies
have unraveled genetic variants associated with cancer driving genes. Systematic
analysis of germline variants from familial cancer syndromes enhances feasibilities of
clinical genetic counseling for hereditary cancers. At the moment, we have several highrisk familial cancer studies under way using next-generation sequencing methods for
case and control samples from the same family. Herein, we present our variant
analyses for familial colorectal cancer (CRC). We have performed exome sequencing of
five Polish families with history of CRC. We mapped exome reads on the reference
human genome. We identified large sets of variants from variant calling. These variants
are initially annotated and characterized with the in-house pipeline. Upon variant
prioritization schema using family history, rarity in the European human population (ESP
and 1000G) and CADD score (>10), we have identified a set of genetic variants which
represent potentially novel predisposing variants for colorectal cancer. For non-coding
regions, we employed a set of the “state-of-the-art” tools (such as FunSeq2, FATHMM,
GWAVA, Haploreg, Oncotactor, regulomeDB, and rSNPbase) for the assessments of
their regulatory nature. We will discuss our results, experiences, challenges and future
perspectives on familial CRC.
18
PostDoc Retreat 2015
T2.7 - Malz, Mona
Academic drug discovery at the DKFZ
Mona Malz, Nikolas Gunkel
Cancer
Drug
Discovery
/
Wirkstoffforschung
Krebsforschungszentrum (DKFZ), Heidelberg, Germany
(G404),
Deutsches
We aim to identify and validate innovative cancer drugs based on new mode of actions.
To this end we collaborate with PIs at the DKFZ, other academic institutes as well as
commercial service providers. To minimize the risk in drug discovery processes, we
developed stringent target validation procedures and target validation criteria. To
access the suitability of a protein as a cancer drug target, we analyze the diseaselinkage of a given target with the help of Tissue-Micro-Arrays (TMAs) to correlate target
expression with clinical data. Furthermore, we apply knockdown, overexpression and
inhibitor based target modulation to access the resulting phenotypic effects in a large
panel of cell lines and assays.
After target validation we develop primary assays (biochemical or cellular), perform
high-throughput screening (HTS) and validate hits using secondary assays, as well as
medicinal chemistry to enhance efficacy and selectivity of our validated hits.
To improve the success probability, we work on several cancer drug targets in parallel,
which are organized in a drug discovery portfolio.
I will describe critical milestones in individual projects, and how we organize drug
discovery projects at the DKFZ.
19
PostDoc Retreat 2015
T3.8 - Breunig, Christian
Regulation of the oncoprotein c-Met in breast cancer and its effect on cell
migration
Christian Breunig1, Julia Greiwe1, Alexander Bott1, Stephan Bernhardt1, Nese Erdem1,
Rainer Will2, Stefan Wiemann1
1
Division of Molecular Genome Analysis, German Cancer Research Center (DKFZ), Im
Neuenheimer Feld 580, 69120 Heidelberg, Germany.
2
Genomics & Proteomics Core Facilities, German Cancer Research Center (DKFZ), Im
Neuenheimer Feld 580, 69120 Heidelberg, Germany.
Breast cancer is the most common cancer in women worldwide with an estimated 1.67
million new breast cancer cases diagnosed in 2012 which makes up 25% of all cancers.
It represents the most frequent cause of cancer death in women in less developed
regions and the second cause of cancer death in more developed regions. One of the
main reasons for its aggressiveness is the formation of metastases via blood and lymph
vessels, which is the leading cause of mortality in patients diagnosed with breast
cancer. Met is a central signaling pathway and can promote cell migration towards the
blood or lymphatic vessels. Here we show that c-Met is elevated in breast cancer with a
basal genotype leading to an enhanced cell migration. Inhibition of c-Met signaling in
invasive breast cancer cell lines reduced HGF mediated signaling and decreased cell
migration. Besides c-Met, members of the TGFβ signaling pathway are also enriched in
basal breast cancer cell lines showing a correlation with c-Met in breast cancer and
other cancer entities cell lines as well as in tissue of breast cancer patients. In this study
we identified that the TGFβ signaling pathway enhances c-Met expression. We are
currently analyzing the effect of TGFβ-induced c-Met expression on cell migration in
human breast carcinoma. Additionally, we identified a miRNA as a posttranscriptional
regulator of c-Met in breast cancer cell lines. This miRNA targeted the 3´untranslated
region of c-Met, showing direct regulation of c-Met. Decreasing c-Met levels by
overexpressing the miRNA in invasive cell lines reduced HGF mediated signaling and
decreased cell migration. In cancer cell lines and in tissue from breast cancer patients
an inverse correlation of c-Met and the miRNA was measured with high expression of cMet and low expression of the miRNA in the aggressive basal breast cancer subtype.
The next step of this project is to co-target TGFβ and c-Met signaling with and without
targeting the miRNA and analyze the effect on breast cancer cell migration.
20
PostDoc Retreat 2015
T3.9 - Fletcher, Michael
de novo transcriptome assembly finds novel glioblastoma subtype-specific
transcripts
Michael Fletcher, Anna Bertoni, Yonghe Wu, Zuguang Gu, Qi Wang, Martje Tönjes,
Marc Zapatka, Carl Herrmann, Bernhard Radlwimmer, Peter Lichter
B060 Molecular Genetics, German Cancer Research Center (DKFZ), Im Neuenheimer
Feld 580, 69120 Heidelberg, Germany.
Glioblastoma is an advanced cancer of the brain with poor prognosis. Hence the need
for better understanding of biology of the tumour is clear. Recent publications have
suggested that adult glioblastoma can be classified into four methylation subtypes. The
HIPO 016 project has produced a rich set of genomic data (WGBS, strand-specific
RNAseq, WES, histone mark ChIPseq) for 48 adult GBMs that is now being analysed to
further characterise these four subtypes. We have established a transcriptome
assembly pipeline using StringTie, followed by differential gene expression analysis with
limma to identify novel subtype-specific transcripts. The pipeline finds about 10000
novel transcripts, 90% of which have not been previously annotated. A majority of these
transcripts appears to be non-coding, with a subset having potential protein domains.
The subtype-specific novel transcripts identified by limma are supported by subtypeenriched histone modifications. A selection of candidate novel transcripts will be further
characterised in silico and, potentially, in cell line models.
21
PostDoc Retreat 2015
T3.10 - Rowald, Konstantina
Selective advantages gained through chromosome instability outweigh fitness
drop during cancer initiation
Konstantina Rowald
(Group of Rocio Sotillo) Mouse Biology Unit; European Molecular Biology Laboratory
(EMBL); Monterotondo, Rome, 00015; Italy
Chromosome instability (CIN) is associated with poor survival and therapeutic outcome
in a number of malignancies. Despite this correlation, CIN can also lead to growth
disadvantages. Here we show that simultaneous overexpression of the mitotic
checkpoint protein Mad2 with KrasG12D or Her2 in mammary glands of adult mice
results in mitotic checkpoint hyper-activation and a delay in tumor onset. Time-lapse
imaging of organotypic cultures and pathologic analysis prior to tumor establishment
reveals error-prone mitoses, mitotic arrest and cell death. Nonetheless, Mad2
expression persists and increases karyotype complexity in Kras tumors. When faced
with the selective pressure of oncogene silencing, Mad2 positive tumors have a higher
frequency of developing resistant subclones that continue to grow despite. Our study
shows that despite the detrimental nature of chromosome missegregation, CIN inducing
genes are selected for during tumor development and contribute to the rapid evolution
of cancer cells. The adaptive capacity of karyotype diversity can hereby both overcome
checkpoint hyper-activation and act as a promoter of oncogene independence. This not
only accounts for the correlation between CIN and therapeutic success, but also points
out the importance of hidden CIN induced mutations as key players of therapy
resistance.
22
PostDoc Retreat 2015
T3.11 - Christopoulos, Petros
A novel thymoma-associated immunodeficiency with increased naive T cells and
reduced CD247 expression
P. Christopoulos1,2 , P. Dopfer3, A. Marx4, W. Schamel3 , P. Fisch1
1
Institute of Pathology, University Medical Center Freiburg.
Current affiliation: Department of Thoracic Oncology, Thoraxklinik at the University
Medical Center Heidelberg; Molecular Thoracic Oncology, German Cancer Research
Center, Heidelberg.
3
Institute of Biology III (Molecular Immunology), Freiburg.
4
Institute of Pathology, University Medical Center Mannheim.
2
The mechanisms underlying thymoma-associated immunodeficiency are largely
unknown and the significance of increased  Τ cells often remains elusive. Here, we
address these questions based on an index patient with thymoma, chronic visceral
leishmaniasis, myasthenia gravis and expanded rare  T-cell subsets in the blood.
This patient showed cutaneous anergy with normal circulating lymphocyte and
CD4+/CD8+ cell counts. Despite chronic infection immunophenotyping and
spectratyping of his lymphocytes revealed an unusual accumulation of naive  and 
T cells, suggesting a generalized T-cell activation defect. Functional studies in vitro
demonstrated substantially diminished IL-2 and IFN- production following TCR
stimulation of his “untouched” naive CD4+ T cells. Biochemical analysis revealed that
his  and  T cells carried an altered TCR complex with reduced amounts of the chain (CD247). No mutations were found in the CD247 gene. The CD247 defect and
increased numbers of  T cells were also observed in thymocyte populations obtained
from 3 other thymoma patients. Thus, our findings describe a novel type of a clinically
relevant acquired T-cell immunodeficiency in thymoma patients that is distinct from
Good’s syndrome. Its characteristics are an accumulation of CD247-deficient,
hyporresponsive naive  and  T cells and an increased susceptibility to infections.
23
PostDoc Retreat 2015
Poster Presentations
Overview
Session
Session 1
Thursday
05.11.2015
15:15-16:30
Session 2
Friday
06.11.2015
10:20-11:15
Poster
Last Name
P1.1
Philipp
Seidel
P1.2
Florian
Neff
P1.3
Margarita
GonzálezValliinas
P1.4
Christine
Engeland
P1.5
Huizi
Wu
P1.6
Magalie
Géraldy
P2.7
Doris
Schneller
P2.8
Barbara
Costa
P2.9
Eva
Nievergall
P2.10
24
First Name
Yasmin
Abassi
Title
Dynamics of chronic DNA-damage
foci and their role for chronic DNAdamage response signalling
Targeting Notch for myeloid
reprogramming in pancreatic cancer
Identification of microRNAs
regulating early spread of lung
adenocarcinoma
Christine Engeland: Oncolytic
Measles Virus for Immunotherapy of
Cancer
Neural crest like genes in melanoma
progression
Development of fluorogenic
thioredoxin reductase (TrxR2)
probes
Role of RAGE and its ligands
S100A8/A9 in hepatocellular
carcinoma onset and development
Lack of CD44 in the brain
parenchyma impairs glioma cell
invasion
Crosstalk between leukemic
progenitors and their stromal niche
in myelodysplastic syndromes and
myeloid leukaemia
Impact of overexpressing mutated KRasG12D and Wnt-1 in lung
cancer initiation, progression and
immune system in vivo
PostDoc Retreat 2015
Poster Presentations
Overview
Session
Session 2
Friday
06.11.2015
10:20-11:15
Session 3
Friday
06.11.2015
14:30-15:30
Poster
First Name
Last Name
P2.11
Mireia
Berdiel Acer
P2.12
Ann-Christin
Gaupel
P2.13
Murat
Iskar
P3.14
Valentina
Kovaleva
P3.15
Ofure
Obazee
P3.16
Daniel
Pastor-Flores
P3.17
Manuel
Rodriguez
P3.18
Kristin
Rattay
P3.19
Somayeh
Pouyanfard
P3.20
Antje
Reuter
Title
Role of ERBB receptors and its
ligands in HER2-low breast cancer.
Specific targeting of ERBB to improve
therapeutic strategies.
Lymphoma – macrophage crosstalk in
diffuse large B cell lymphoma
Deregulated DNA methylation in CLL
from bisulfite sequencing
Metaplastic breast carcinomas exhibit
case-matched mutational patterns
linked to distinct morphologies by
targeted NGS
Novel pancreatic cancer susceptibility
loci discovered through genome-wide
association studies
roGFP2-Tsa2ΔCR, a novel
ultrasensitive peroxiredoxin-based
H2O2 probe
Reduced DNA methylation patterning
defines epigenetic drift during human
aging skin
Promiscuous gene expression in
mTECs is a highly coordinated and
evolutionary conserved process
Improvement of the Immunogenicity of
Thioredoxin-L2 Peptide as a
Prophylactic Cervical Cancer Vaccine
using the IMX313-T Antigen Reengineering Platform.
Virus-Associated Carcinogenesis
25
PostDoc Retreat 2015
P1.1 - Seidel, Philipp
Dynamics of chronic DNA-damage foci and their role for chronic DNA-damage
response signalling
Philipp Seidel, Julian Schlegel, Amir Abdollahi
Molecular & Translational Radiation Oncology, National Center for Tumor Diseases,
German Cancer Research Center, 69120 Heidelberg, Germany
DNA-damage foci (DDF) are chromatin domains that form at sites of DNA double-strand
breaks (DSB). Recently, persistent DDF (pDDF) have gained increased attention as
chronic nuclear marks, which can be induced by radio- or chemotherapeutic regimens,
but also by cell-intrinsic mechanisms (e.g. telomere erosion) and have been linked to
senescence-associated growth-arrest. To gain insight into the potential role of pDDF
during tumor development and therapy, we aimed to determine pDDF properties and
functions in tumor cells employing ionizing radiation (IR) as a genotoxic source.
Via time-lapse microscopy, we found that increased compartmental size and high
spatiotemporal stability are major determinants of pDDF. Activated phospho-p53
accumulated within pDDF and p53 expression was linked with nuclear accumulation of
p21, reduced proliferation and reduced reproductive potential, suggesting a tumorsuppressor role of pDDF. Endogenous pDDF were prevalent in tumor cell lines of
various origins and correlated inversely with p53 activity. pDDF-positive cells underwent
mitosis and generated pDDF-positive cell progeny, as determined by time-lapse
microscopy, suggesting that pDDF prevail in proliferating cell populations for many
generations instead of occurring dynamically via de-novo formation. pDDF analysis on
condensed metaphase chromosomes that both endogenous and IR-induced pDDF
occur mainly, but not exclusively at chromosome ends and close to centrosomes. pDDF
in internal chromosomal positions do not show apparent signs of DSB. Together, this
explains why pDDF do not necessarily interfere with DNA replication and chromosome
segregation. However, pDDF showed a finite life time when generated via high-dose IR
in pDDF-negative cell lines. Nevertheless, cell populations exhibiting long-term pDDF
retention could be generated via clonal selection of pDDF-positive single cells, via
repeated low-dose irradiation or via inactivation of p53. This suggests that tumor cells in
development or therapy depending on their p53 status respond fundamentally different
in terms of pDDF accumulation, with potential implications for inflammatory status,
malignant traits and therapy resistance.
26
PostDoc Retreat 2015
P1.2 - Neff, Florian
Targeting Notch for myeloid reprogramming in pancreatic cancer
Florian Neff1,2,3,4, David G. Kirsch5, Dieter Saur1,3,4, Roland Schmid1,3,4, Alexander
Bazhin6, Mathias F. Heikenwälder3,7, Jens T. Siveke1,2,3,4
1
German Cancer Consortium (DKTK), Germany.
Division of Translational Solid Tumor Oncology, University Hospital Essen, Germany.
3
German Cancer Research Center (DKFZ), Heidelberg, Germany.
4
Medical Department, Klinikum rechts der Isar, Technische Universität München,
Munich, Germany.
5
Department of Radiation Oncology, Duke University Medical Center, Durham, NC,
USA.
6
Department of General, Visceral, Transplantation, Vascular and Thoracic Surgery,
Hospital of the University of Munich, Germany.
7
Institute of Virology, Technische Universität München/Helmholtz Zentrum München,
Munich, Germany.
2
Pancreatic ductal adenocarcinoma (PDAC) is characterized by two major hallmarks.
First, insufficient therapeutic treatment options leading to poor prognosis and short
survival rates and second, a complex stromal reaction quantitatively exceeding the one
found in other tumors by far. A progressive immune cell accumulation associated with
PDAC development suggests multiple potential targets for immunotherapeutic
interventions. Despite in many other solid tumors, however, therapeutic immune
checkpoint blockade failed in clinical trials of human PDAC highlighting the urgent need
for in-depth analysis of PDAC-associated immune networks.
27
PostDoc Retreat 2015
P1.3 - González-Vallinas, Margarita
Identification of microRNAs regulating early spread of lung adenocarcinoma
Margarita González-Vallinas1, Marco Albrecht2, Adriana Pitea3, Jennifer Schmitt1,
Thomas Muley4,5, Michael Meister4,5, Arne Warth1,5, Peter Schirmacher1, Nikola S.
Mueller3, Franziska Matthäus2, Kai Breuhahn1
1
Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany.
Center for Modeling and Simulation in the Biosciences (BIOMS), University of
Heidelberg, Heidelberg, Germany.
3
Institute of Computational Biology, Helmholtz Center Munich, German Research
Center for Environmental Health, Neuherberg, Germany.
4
Translational Research Unit, Thoraxklinik at the University Hospital Heidelberg,
Germany.
5
Translational Lung Research Centre Heidelberg (TLRC-H), member of the German
Center for Lung Research (DZL), Germany.
2
MicroRNAs (miRNAs) are important regulators of gene expression at the transcriptional
and translational levels, and they regulate many cancer processes including invasion
and metastasis. In this work, we aimed to identify miRNAs involved in the early spread
of lung adenocarcinoma. To that end, we firstly analyzed miRNA sequencing data
(Illumina HiSeq platform) from a patient cohort of The Cancer Genomic Atlas (TCGA)
database (n=449) to determine miRNAs differentially expressed in tumors from patients
with lymph node metastasis (stages N1, N2, and N3) compared to non-metastasized
tumors (N0). The consistent dysregulation (up or down) in tumors versus matched
healthy tissue samples (n=39) was additionally considered to filter the results. Following
this approach, we identified 23 miRNAs significantly dysregulated in lymph node
metastasis (p<0.05). The results were further validated by qRT-PCR analysis of freshfrozen tumor samples from an independent lung adenocarcinoma patient cohort of the
Thoraxklinik Heidelberg (n=108). Integrative analysis of miRNA and mRNA data used
for target prediction pointed to several metastasis-related genes as potential targets of
the selected miRNAs. In summary, our results show a set of miRNAs associated to lung
adenocarcinoma spread with potential for therapeutic targeting and cancer biomarker
development, warranting additional studies for their functional characterization.
28
PostDoc Retreat 2015
P1.4 - Engeland, Christine
Christine Engeland: Oncolytic Measles Virus for Immunotherapy of Cancer
Christine E. Engeland1, 2, Rūta Veinalde1, Tobias Speck1, Johannes Heidbüchel1,
Christian Grossardt1, Dirk Jäger2, Christof von Kalle1, Guy Ungerechts1, 2
1
National Center for Tumor Diseases Heidelberg, Department of Translational
Oncology, German Cancer Research Center, Im Neuenheimer Feld 460, 69120
Heidelberg, Germany.
2
National Center for Tumor Diseases Heidelberg, Department of Medical Oncology, Im
Neuenheimer Feld 460, 69120 Heidelberg, Germany
Oncolytic viruses which selectively replicate and spread in malignant tissues are
currently evaluated in clinical trials. Aside from tumor reduction by direct cytopathic
effects, oncolytic viruses can induce a tumor-specific immune response. During
oncolysis, tumor-associated antigens are released in an immunostimulatory context,
which can be considered as an “in situ tumor vaccine”.
Several strategies are currently pursued to further enhance tumor-directed
immunological effects of virotherapy. For instance, cytokines such as interleukin-12 can
be encoded within the viral genome to direct the anti-tumor response towards a
favorable Th1 phenotype. Virus-encoded bispecific T cell engagers can be employed to
redirect T cells to tumor cells. Furthermore, virus-encoded tumor-specific antigens can
further stimulate anti-tumor immune responses.
Combining oncolytic Measles virus (MeV) with immune checkpoint blockade can
provide synergistic anti-tumor effects. We generated immunomodulatory MeV encoding
anti-CTLA-4, anti-PD1 or anti-PD-L1 antibodies and tested their therapeutic effects in
murine tumor models. Treatment with MeV-anti-CTLA-4 and MeV-anti-PD-L1 led to an
increased ratio of T effector to regulatory T cells. Delayed tumor progression and
prolonged median overall survival were observed for animals treated with MeV-antiCTLA-4 and MeV-anti-PD-L1, respectively. Based on these results, we are currently
preparing a clinical trial at the National Center for Tumor Diseases.
29
PostDoc Retreat 2015
P1.5 - Wu, Huizi
Neural crest like genes in melanoma progression
Huizi Wu, Lionel Larribere, Jochen Utikal
Clinical Cooperation Unit DermatoOncology, G300, Im Neuenheimer Feld 280, 69120
Heidelberg.
Melanoma is the most aggressive skin cancer transformed from melanocytes, which are
derived from the embryonic neural crest. The biggest challenge of melanoma is poor
efficiency of available treatment for advanced disease and metastatic melanoma.
Despite much important work on melanoma, we still lack of the development of effective
treatment. Melanoma is the malignant transformation of melanocytes, therefore
understanding the development of melanocytes helps us to better understand
melanoma pathogenesis.
The Neural crest is a transient embryonic cell population originating from the ectoderm,
in a region lateral to the prospective neural plate. Neural crest cells have a migratory
competence and show a loss of intercellular adhesion which allows them to emigrate
from the neural tubes. During the development, neural crest progenitor cells down
regulate cell adhesion molecules such as E-cadherin to undergo an epithelial-tomesenchymal transition in order to migrate. In this project, we investigate the genes
aberrantly expressed in Neural crest cells and melanoma cells to understand the
mechanism involved in melanoma cells de-differentiation.
30
PostDoc Retreat 2015
P1.6 - Géraldy, Magalie
Development of fluorogenic thioredoxin reductase (TrxR2) probes
Magalie N. E. Géraldy, Aubry Miller
DKFZ - Cancer Drug Discovery, Im Neuenheimer Feld 280, D-69120 Heidelberg.
The selenoprotein thioredoxin reductase, which presents two subtypes (TrxR1 &
TrxR2), plays a key role in regulating cellular redox homeostasis and has attracted
increasing attention as a promising anticancer drug target . The first published
fluorescent probe for mammalian TrxR is TRFS-green . This compound is composed of
a 1,2-dithiolane moiety attached to a naphthalimide fluorophore. TRFS-green displays a
green fluorescence off−on change induced by the TrxR-mediated disulfide cleavage
and subsequent intramolecular cyclization to liberate the masked fluorophore. It was
demonstrated in vitro that TRFS-green is highly selective toward TrxR. A specific
improvement of these results toward TrxR2 would consist in the synthesis of a TRFSgreen derivative containing a mitochondrially targeted lipophilic triphenylphosphonium
(TPP) cation . The synthesis of some other fluorescent probes derived from fluorescein
or Tokyo green and containing a 1,2-dithiolane and TPP scaffolds is ongoing.
Dithiaarsanes Induce Oxidative Stress-Mediated Apoptosis in HL-60 Cells by Selectively Targeting
Thioredoxin Reductase, Y. Liu, D. Duan, J. Yao, B. Zhang, S. Peng, H. Ma, Y. Song, J. Fang, J. Med.
Chem. 2014, 57, 5203 − 5211.
Highly Selective Off−On Fluorescent Probe for Imaging Thioredoxin Reductase in Living Cells, L.
Zhang, D. Duan, Y. Liu, C. Ge, X. Cui, J. Sun, J. Fang, J. Am. Chem. Soc. 2014, 136, 226 – 233.
Small-Molecule Targeting of the Mitochondrial Compartment with an Endogenously Cleaved
Reversible Tag, J. Ripcke, K. Zarse, M. Ristow, M. Birringer, ChemBioChem 2009, 10, 1689 – 1696.
31
PostDoc Retreat 2015
P2.7 - Schneller, Doris
Role of RAGE and its ligands S100A8/A9 in hepatocellular carcinoma onset and
development
Aurora De Ponti, Doris Schneller, Tobias Pusterla, Lars Wiechert, Thomas Longerich,
Arndt Vogel, Eli Pikarsky, Jochen Hess, Peter Angel
The Receptor for Advanced Glycation-End products (RAGE) is a multi-ligand receptor,
mainly involved in tissue damage and inflammatory disorders. RAGE and its ligands
S100A8 and S100A9 have been shown to be overexpressed in tumors, including
hepatocellular carcinoma (HCC), enhancing cancer progression and metastasis by still
unknown mechanisms.
To address the role played by RAGE and S100A8/A9 in HCC onset and development,
we took advantage of two mouse models: (i) the multidrug resistance 2 knock-out
(Mdr2-/-) mouse and (ii) treatment with the procarcinogen diethylnitrosamine (DEN).
The Mdr2-/- mouse shows chronic hepatitis, liver damage and fibrosis followed by HCC
development. On the other side, DEN is an alkylating agent that promotes DNA-strand
breaks, thus leading to HCC formation in a cirrhosis-free context.
- Regarding HCC onset, we will investigate the role of RAGE and S100A8/A9 in HCC
progenitor cells (HcPCs). It was already shown that HcPCs can be isolated from
different mouse models, and that cells resembling HcPCs reside within dysplastic
lesions that appear several months before HCC nodules.
- Regarding HCC development, we demonstrated that Rage ablation impaired tumor
development only in the Mdr2-/- model, where it reduced number and size of tumors
and limited liver damage and oval cell activation. On the contrary, absence of S100a9 in
the Mdr2-/- model did not affect HCC development nor liver damage, but lack of this
protein significantly reduced the size of tumors in the DEN model.
These unexpected results underline the complexity of the cross-talk between RAGE and
its ligands, which orchestrate neoplastic transformation and malignant progression.
They also highlight the necessity of using more sophisticated genetic models in order to
decipher the contribution of each ligand and receptor involved in HCC development.
32
PostDoc Retreat 2015
P2.8 - Costa, Barbara
Lack of CD44 in the brain parenchyma impairs glioma cell invasion
Barbara Costa1, Jasmin Meckler1, Tanja Eisemann1, Ingrid Spaan1, Giuseppina Pace2,
Olivier Armant2, Veronique Orian-Rousseau2, Peter Angel1, Heike Peterziel1
1
Transduction and Growth Control, DKFZ/ZMBH Alliance, Heidelberg, Germany.
Institute of Toxicology and Genetics, KIT, Karlsruhe, Germany.
2
High grade gliomas are the most prevalent and lethal form of tumors within the human
central nervous system. Their dismal prognosis relies on the aggressive growth and
invasiveness, which enable tumors to escape complete surgical resection, chemo- and
radiotherapy. The ability to invade normal surrounding tissue is mediated by the crosstalk of tumor cells with the tumor microenvironment (TME). In this process surface
receptors and adhesion molecules play an important role.
CD44 is an adhesion transmembrane protein expressed at high levels in glioma cells
however, its expression is also induced in reactive astrocytes and microglia in different
pathological conditions including glioma lesions. So far most studies addressed the role
of CD44 in tumor cells, whereas the contribution of CD44 expression in TME is poorly
characterized.
Employing spheroid migration assays on organotypic brain slice cultures we observed
that all glioma cell lines tested are able to invade the normal brain tissue. However,
when spheroids were implanted in brain slices derived from CD44 deficient mice, the
migration of the majority of glioma cell lines was heavily impaired. These data suggest
the existence of a TME-CD44-dependent mechanism promoting tumor cell invasion into
brain tissue.
Endothelial-specific deletion of CD44 in brain slices did not interfere with spheroid
migration indicating that CD44 on endothelial cells is not essential for glioma cell
migration.
Additional experiments aim to identify the specific cell type harbouring the rate -limiting
function of CD44 to mediate glioma cell invasion. Furthermore, comparative
transcriptome analyses of TME-CD44-dependent and -independent glioma cell lines will
identify putative CD44-interacting molecules on the tumor cells.
Altogether our data will contribute to characterize a novel mechanism of glioma-TME
interaction which promotes tumor cell invasion and will clarify whether glioma patients
may benefit from an anti CD44 therapy, not only by targeting glioma cells, but also by a
TME- directed approach.
33
PostDoc Retreat 2015
P2.9 - Nievergall, Eva
Crosstalk between leukemic progenitors and
myelodysplastic syndromes and myeloid leukaemia
their
stromal
niche
in
Eva Nievergall1, Simon Raffel2, Maximillian Mossner3, Hind Medyouf4, Tobias Boch3,
Wolf-Karsten Hofmann3, Daniel Nowak3 and Andreas Trumpp1,2
1
Division of Stem Cells and Cancer, Deutsches Krebsforschungszentrum (DKFZ),
Heidelberg, Germany.
2
Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM
gGmbH), Heidelberg, Germany.
3
Department of Hematology and Oncology, University Hospital Mannheim, Medical
Faculty Mannheim of the University of Heidelberg, Mannheim, Germany.
4
Georg-Speyer-Haus, Institute for Tumor Biology and Experimental Therapy, University
of Frankfurt, Frankfurt.
Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal haematopoietic
stem cell disorders, which mainly affect elderly people. With an estimated 3-year
survival rate of 45% MDS are either indolent or progress to bone marrow failure or
Acute Myeloid Leukaemia.
Previous work in our group has established a xenograft model of low-risk MDS by cotransplanting MDS progenitor cells with autologous mesenchymal stromal cells (MSCs)
into NSG mice and verified a crucial role of microenvironmental cues in the
maintenance of MDS.
We are now aiming to decipher the underlying mechanisms of the leukemic progenitor –
MSC crosstalk, for example by genetically interrogating the role of SPARC and other
ECM proteins, which are differentially expressed in MDS MSCs compared to healthy
donor MSCs.
To better recapitulate the human bone marrow niche we are developing an ectopic bone
marrow niche model, which will be ideally suited to study the reprogramming of the
microenvironment and to test putative therapeutic targets that may interfere it.
By improving our understanding of leukemic niches we aim to aid the discovery and
development of innovative MSC-targeted therapies as targeting the bone marrow
microenvironment in addition to the leukemic cells may prevent disease relapse and
improve outcomes of MDS patients.
34
PostDoc Retreat 2015
P2.10 - Abassi, Yasmin
Impact of overexpressing mutated K-RasG12D and Wnt-1 in lung cancer initiation,
progression and immune system in vivo
Yasmin Abassi1,2, Fulvia Vascotta2, Yves Hüsemann3, Mustafa Diken2, Sebastian
Kreiter2,3, Sebastian Attig2,3, Steffen Lorenz4, Jeffrey A. Whitsett5, Lewis A. Chodosh6,
Stefan Liebner7, Rajkuma Savai8, Aleksandra Tretyn8, Harald Binder9, Johanna Mazur9,
John Castle2, Ugur Sahin2,3, Ernst-Otto Bockamp2,10
1
Division Signaltransduction and Growth Control, German Cancer Research Center,
DKFZ, Heidelberg, Germany.
2
TRON – Translational Oncology at Johannes Gutenberg University Medical Center
gGmbH, Mainz, Germany.
3
BioNTech RNA Pharmaceuticals GmbH, Mainz, Germany.
4
Department of Internal Medicine, Gastroenterology, Johannes Gutenberg University
Medical Center, Mainz, Germany.
5
Department of Pulmonary Biology, Cincinnati Children’s Hospital Medical Center and
University of Cincinnati college of Medicine, Cincinnati, OH, USA.
6
Departments of Cancer Biology , Cell and Developmental Biology, and Medicine, and
The Abramson Family Cancer Research Institute, University of Pennsylvania School of
Medicine, Philadelphia, PA 19104-6160 USA.
7
Edinger-Institut, Medical center of J.W.Goethe Frankfurt University, Frankurt am Main,
Germany.
8
Max-Planck-Institut of Heart and Lung Research, Bad-Nauheim, Germany.
9
Institute of Medical Biostatistics, Epidemiology and Informatics, IMBEI, Johannes
Gutenberg University Medical Center, Mainz, Germany.
10
Institute of Translational Immunology, TIM, Johannes Gutenberg University Medical
Center, Mainz, Germany.
Clinical studies demonstrated a link between ectopic expression of Wnt-1 ligand in lung
tumor samples and poor survival of patients suffering from non-small cell lung cancer
(NSCLC). However, the molecular mechanisms underlying the synergy between ectopic
Wnt-1 expression and malignant NSCLC progression have not been clearly delineated.
Since WNT-components have been reported to modulate the immune system by
directly targeting dendritic cells, macrophages and T cells, one attractive possibility
explaining the worse prognosis of WNT-1+ lung cancer patients is that aberrant
expression of WNT-1 decreases the anti-tumor immune surveillance and thus prevents
the normal recognition and elimination of cancer cells by the immune system. To
investigate the functional role of ectopic Wnt-1 expression during lung cancer, we have
used an autochthonous mouse model that allowed the conditional expression of Wnt-1
and oncogenic K-RasG12D in lung epithelial cells. Using this in vivo approach, it was
possible to clarify several fundamental principles: (i) overexpression of Wnt-1 in lung
35
PostDoc Retreat 2015
P2.10 - Abassi, Yasmin
epithelial cells was not sufficient to promote tumor growth. (ii) Concomitant expression
of Wnt-1, together with oncogenic K-RasG12D promoted a fulminant tumorigenesis
being by far more aggressive than the tumor development that was induced by KRasG12D alone. (iii) Comparison of the immune cell microenvironment in K-RasG12D
and Wnt-1/KRasG12D lung tumors revealed several striking differences in the
frequency and distribution of immune cells such as the massive infiltration of mast cells
in Wnt-1/K-RasG12D tumors and the complete absence of these cells in K-RasG12D
tumors. (iv) Proteomic and NGS-based mRNA analysis further demonstrated important
differences between the two models. Most remarkably, a reduction of proinflammatory
cytokines and chemokines was evident when K-RasG12D and Wnt-1/K-RasG12D lung
tumors were compared. (vii) Finally, syn- and allogenic tumor cell (lewis lung cancer cell
line, LLC) rejection experiments revealed that overexpression of Wnt-1 in the lung
prevented the rejection of LLC cells in non-genetically matched recipients and resulted
in lung tumor development. These findings suggest a novel and so far unrecognized
immune suppressive mechanism of Wnt-1, capable of negatively influencing normal
anti-tumor surveillance mechanisms and thus promoting faster and more aggressive
lung tumor formation. It will now be important to develop novel therapeutic stratigies
capable of blocking Wnt-1 function and to test wether such a therapeutic approch can
provide clinical benefit to WNT-1+ lung cancer patients.
36
PostDoc Retreat 2015
P2.11 - Berdiel Acer, Mireia
Role of ERBB receptors and its ligands in HER2-low breast cancer. Specific
targeting of ERBB to improve therapeutic strategies.
Berdiel, M.1, Reinz, E.1, Breunig, C.1, Bott, A.1, Mitra, D.1; Sofyali, E.1, Burmester, S.1,
Will, R.2, Hasmann, M.3, Korf, U.1, Wiemann, S.1
1
Division Molecular Genome Analysis, DKFZ, Heidelberg
Genomics and Proteomics Core Facility, DKFZ, Heidelberg
3
Roche Diagnostics, Penzberg
2
About 70-80% of primary breast tumors show low or no detectable expression of HER2
receptor. However, other members of the ERBB family of receptors tyrosine kinases (RTK) such
as EGFR, ERBB3 and ERBB4, are frequently potent drivers of tumor progression, resistance
and metastasis. Although treatment of patients expressing high levels of HER2 is well
established, an elevated percentage of patients develop resistance to anti-HER2 targeted
therapies. On the other hand, current treatment options for tumors expressing HER2 at low to
moderate levels have been proven unsuccessful, claiming for new therapeutic strategies.
Signaling via receptors of the ERBB family is wired within a complex network of cellular back-up
routes that can maintain downstream signaling pathways. Even the inhibition of a single
receptor commonly leads to the activation of other receptors maintaining signaling and
phenotypes. Drug impact on signaling networks needs to be understood in the context of
activating ligands derived by autocrine or paracrine mechanisms and by the tumor
microenvironment. The HER2Low project aims to identify the tumorogenic role of the different
ERBB members (mainly ERBB3 and ERBB4) and its ligands in a panel of cell lines under the
HER2 low/moderate background and also to define alternative therapeutic strategies.
Cancer cell lines (e.g., T47D, MDA-MB-231, MCF7) were selected according to their HER2
low/moderate expression (Neve RM. Cancer cell, 2006) and were molecularly characterized by
means of RT-PCR and western blot analysis. Whereas T47D and MCF7 showed elevated
expression of ERBB3 and ERBB4, in MDA-MB-231 only EGFR was expressed at high levels.
Treatment with anti-HER2 therapies in these cell lines did not induce changes in viability,
confirming their independence of HER2 receptors. To study the role of ERBB receptors on
resistance mechanisms, trastuzumab-resistant BT474 cell line (BT474 TrasR ) and tamoxifenresistant MCF7 cell (MCF7 TamR ) were also included. While expression of ERBB3 and
ERBB4 receptors in tamoxifen-resistant MCF7 (MCF7 TamR ) was increased compared with
parental MCF7, in BT474 Trast R these receptors were mostly decreased.
Because NRG1 is the preferred ligand for ERBB3 its impact on cancer cells was further
explored. Stimulation of T47D and MCF7 with NRG1 increased its proliferation and induced
phosphorylation of the PI3K-AKt pathway. Not effects were observed for MDA-MB-231.
Expression of NRG1 in epithelial cancer cells showed to be very low and inversely correlated
with ERBB3 and ERBB4 expression, suggesting the microenvironment as a main source for this
ligand.
The ERBB3/ERBB4-NRG1 axis appears to be highly relevant both for tumor progression and
drug resistance. Its specific blockade using targeted therapeutic antibodies might be a
promising strategy for treatment of HER2-low subtypes of breast cancer and will be further
explore in the HER2 low project.
37
PostDoc Retreat 2015
P2.12 - Gaupel, Ann-Christin
Lymphoma – macrophage crosstalk in diffuse large B cell lymphoma
Ann-Christin Gaupel, Martina Seiffert* and Bernhard Radlwimmer*
Division of Molecular Genetics, German Cancer Research Center, Heidelberg,
Germany
* Co-last authors
Diffuse large B cell lymphoma (DLBCL) is the most common B-cell non-Hodgkin
lymphoma, encompassing 30 to 40% of all new cases. The standard treatment regimen
is a combination of chemotherapy and immunotherapy, the anti-CD20 antibody
Rituximab. While the majority of patients can be cured, thirty percent of the patients
relapse or do not respond to therapy.
DLBCL is characterized by large numbers of malignant B cells that destroy the normal
lymph node architecture. While DLBCL is regarded as more autonomous compared to
other lymphomas, e.g. follicular lymphoma and Hodgkin’s lymphoma, several studies
indicate that the tumor microenvironment does support the DLBCL cells. For example,
stromal gene expression signatures have been shown to predict survival and the
presence of M2 macrophages is associated with poor outcome.
We are analyzing the interplay between macrophages and lymphoma cells to identify
new treatment approaches. Using in vitro co-culture systems, followed by gene
expression profiling and secretomics, we will identify the major players in this crosstalk
and the changes, that are inflicted in the two cell types.
38
PostDoc Retreat 2015
P2.13 - Iskar, Murat
Deregulated DNA methylation in CLL from bisulfite sequencing
Murat Iskar, Marc Zapatka, Volker Hovestadt, Naveed Ishaque, Jan-Philipp Mallm,
Sandra Koser, Jose Muino, Vladimir Teif, Sabrina Kugler, Peter Lichter, Karsten Rippe,
Daniel Mertens
Division of Molecular Genetics, German Cancer Research Center (DKFZ), Im
Neuenheimer Feld 280, Heidelberg 69120, Germany.
B-cell chronic lymphocytic leukemia (CLL) is the most common leukemia among adults
in western world but still our understanding of the molecular mechanisms that determine
the disease state is limited. CLL is one of the cancers that show low mutation
recurrence, and it was proposed that global and gene-specific epigenetic modifications
might contribute to the pathogenesis of CLL substantially. In Cancerepisys consortium,
DNA methylation, transcriptome, nucleosome positioning and histone modification
profiles were generated for B and T cells of CLL patients and healthy donors. Our main
goal is to identify key epigenetic events that drive tumorigenesis in these cancers using
an integrative approach. We are specifically interested in global changes in DNA
methylation and their relation with genomic alterations and expression changes. To this
end, we first processed the WGBS data from CLL patients and healthy B and T cells
using methylCtools. Landau et al. (Cancer Cell, 2014) has reported that the stochastic
disordered methylation was the main driver of high intrasample variability of DNA
methylation observed in majority of CLL cases. To comprehensively define and quantify
the stochastic disordered methylation, we sought to identify partially methylated
domains (PMD, >100kb) and DNA methylation valleys (DMV, >5kb) in CLL and healthy
samples. Our genome-wide comparison has revealed that PMDs constitute a large
fraction of CLL genomes (~45%) in comparison to healthy B and T cells (<1%). We
further integrated the DNA methylation profiles with the differentially expressed genes
derived from the RNA-seq data and found that the down-regulated genes were
significantly enriched within PMDs. We next investigated the chromatin states of CLL
and healthy samples to understand the underlying regulatory mechanism of tumor
specific PMDs. Our genome-wide analysis has delineated the prevalent aberrations in
CLL methylome that can shed light on the role of epigenetic regulation in the
pathogenesis of CLL.
39
PostDoc Retreat 2015
P3.14 - Kovaleva, Valentina
Metaplastic breast carcinomas exhibit case-matched mutational patterns linked to
distinct morphologies by targeted NGS
V. Kovaleva*, 1, 2, K. Werner*, 1, P. Bronsert1, 3, W. Weichert2,4, M. Kriegsmann1, 4, M.
Hirschfeld2, 5, E. Stickeler2,3,5, S.Laßmann1,2,3, M. Werner1,2,3
1
Institute of Surgical Pathology, University Medical Center, Freiburg, Germany.
German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ)
Heidelberg, Germany.
3
Comprehensive Cancer Center, University Medical Center, Freiburg, Germany.
4
Institute of Pathology, Ruprecht-Karls-University, Heidelberg, Germany.
5
Department of Obstetrics and Gynecology, University Medical Center, Freiburg,
Germany
*
contributed equally
2
Metaplastic carcinoma of the breast (MCB) is a rare subtype of breast cancer,
characterized by high level of tumor heterogeneity, aggressive growth, few therapeutic
options and hence poor outcome. This study addressed mutational profiles of distinct
MCB differentiation patterns to identify potential novel targetable MCB (sub)clones
according to intratumoral morphology.
We examined a series of 24 MCB cases with following components: ductal
differentiation, spindle cell carcinoma, fibromatosis-like, chondroid, squamous and
osseous. DNA isolated from microdissected distinct morphological components was
analyzed by Truseq Amplicon Cancer Panel (Illumina). Evaluation of somatic mutations
was performed by MiSeq Reporter, VariantStudio and IGV and their validation for
selected genes by Sanger sequencing.
Profiling by tNGS yielded informative data in 23/24 cases, corresponding to 47/54
analyzed morphological components thereof. Unique case-specific mutation profiles
were revealed for most of the cases (22/23). In contrast, there was no marked overlap
of specific mutations in the distinct morphologies when neglecting case-specificity.
Important case-specific mutations occurring in all morphological components were in
TP53 (10/23), PIK3CA (2/23) and JAK3 (1/23). PIK3CA mutation, p.H1047R, was at
known hotspot of kinase domain. The JAK3, p.V722I, mutation was in pseudokinase
domain.
This study demonstrated for the first time mutational profiles in distinct morphological
components of MCB by tNGS. Specifically this analysis revealed that mutational status
is rather case- than cell differentiation-specific. Moreover, besides other genes the study
shows mutated PIK3CA and JAK3 as potential therapy relevant candidates so far nontargetable MCBs.
40
PostDoc Retreat 2015
P3.15 - Obazee, Ofure
Novel pancreatic cancer susceptibility loci discovered through genome-wide
association studies
Ofure Obazee1, Daniele Campa1,2, Cosmeri Rizzato1,2, Maarten F. Bijlsma3, Hermann
Brenner1, H. Bas Bueno-de-Mesquita4, Gabriele Capurso5, Giulia Martina Cavestro6,
Niccola Funel7, Maria Gazouli8, Thilo Hackert9, Timothy J. Key10, Juozas Kupcinskas11,
Stefano Landi2, Ewa Malecka-Panas12, Andrea Mambrini13, Beatrice MohelnikovaDuchonova14, John P. Neoptolemos15, Claudio Pasquali16, Raffaele Pezzilli17, Aldo
Scarpa18, Oliver Strobel9, Francesca Tavano19, Yogesh K. Vashist20, Pavel Vodicka21,
PanScan Consortium, PanC4 Consortium, Rachael Stolzenberg-Solomon22, Brian
Wolpin23, Alison Klein24, Laufey Amundadottir22, Federico Canzian1
1
German Cancer Research Center (DKFZ), Heidelberg, Germany.2University of Pisa, Pisa,
Italy.3Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands.4National
Institute for Public Health and the Environment (RIVM), Bilthoven, Netherlands.5“Sapienza”
University of Rome, Rome, Italy.6Università Vita Salute San Raffaele and IRCCS Ospedale San
Raffaele, Milan, Italy.7University Hospital of Pisa, Pisa, Italy.8University of Athens, Athens,
Greece.9University Hospital Heidelberg, Heidelberg, Germany.10University of Oxford, Oxford,
U.K.11Lithuanian University of Health Sciences, Kaunas, Lithuania.12Medical University of Lodz,
Lodz, Poland.13ASL1 Massa Carrara, Massa Carrara, Italy.14Institute of Public Health, Prague,
Czech Republic.15University of Liverpool, Liverpool, U.K.16University of Padua, Padua,
Italy.17Sant'Orsola-Malpighi Hospital, Bologna, Italy.18University and Hospital Trust of Verona,
Verona, Italy.19IRCCS Scientific Institute and Regional General Hospital “Casa Sollievo della
Sofferenza”, San Giovanni Rotondo, Italy.20University Medical Center Hamburg-Eppendorf,
Hamburg, Germany.21Institute of Experimental Medicine, Academy of Sciences, Prague, Czech
Republic.22National Cancer Institute, Bethesda, MD, USA.23Dana Farber Cancer Institute,
Boston, MA, USA.24Johns Hopkins School of Medicine, Baltimore, MD, USA.
Introduction: Previous genome-wide association studies (GWAS) have identified several regions
convincingly or putatively associated with pancreatic cancer risk. However, estimates of
heritability suggest that a large number of loci remain to be discovered.
Aims: To identify additional susceptibility loci, the PANcreatic Disease ReseArch (PANDoRA)
consortium participated in two additional GWAS, PanScan3 and PanC4, with USA-based
consortia.
Materials and methods: A total of over 5,700 pancreatic cancer cases and almost 9,000 healthy
controls were genotyped with genome-wide arrays by PanScan and PanC4. Results of the two
series were meta-analyzed with those from previous GWAS (PanScan1 and PanScan2), and
the top candidates were then genotyped in over 2,500 pancreatic cancer cases and 4,000
controls from the PANDoRA consortium.
Results: Nine new loci reached genome-wide statistical significance (p<5x10-8) for association
with pancreatic cancer risk, and four more approached genome-wide significance.
Conclusion: These studies doubled the number of known susceptibility alleles for pancreatic
cancer.
41
PostDoc Retreat 2015
P3.16 - Pastor-Flores, Daniel
roGFP2-Tsa2ΔCR, a novel ultrasensitive peroxiredoxin-based H2O2 probe
In the last decade, hydrogen peroxide has emerged as an important intracellular
signaling molecule. However, the study of H2O2 signaling has been hampered by the
lack of a non-invasive, highly sensitive H2O2 probe. While the current generation of
genetically encoded fluorescent probes allow dynamic real-time measurements of
pronounced oxidative events, e.g. in the course of Nox activation, they do not provide
sufficient sensitivity to monitor fundamental metabolic variations in base-line H2O2
levels (presumably taking place in the nanomolar range). We developed a novel ultrasensitive probe based on roGFP2 and the yeast 2-Cys peroxiredoxin Tsa2 that allows
monitoring minute changes in basal levels of H2O2 from the yeast system to higher
eukaryotes organisms.
42
PostDoc Retreat 2015
P3.17 - Rodriguez, Manuel
Reduced DNA methylation patterning defines epigenetic drift during human aging
skin
Manuel Rodríguez-Paredes1,2, Felix Bormann1, Julian Gutekunst1, Lars Kaderali3, Marc
Winnefeld4 and Frank Lyko1
1
Division of Epigenetics, DKFZ-ZMBH Alliance, German Cancer Research Center,
Heidelberg, Germany.
2
University Tumor Center Duesseldorf, University of Duesseldorf, Medical Faculty,
Duesseldorf, Germany.
3
Institute for Medical Informatics and Biometry, University of Technology Dresden,
Germany.
4
Research & Development, Beiersdorf AG, Hamburg, Germany.
DNA methylation is essential for differentiation and cell-type specification, and its
disruption is involved in many human diseases. DNA methylation changes are also a
hallmark of aging, but the role of these aberrancies in this context, sometimes called
“epigenetic drift”, is considerably less understood. Skin has always been used for aging
research due to economical or medical reasons but, as the body´s first line of defense, it
is also a perfect model for studying the environmental effects on epigenetics. Herein, we
used Infinium 450K microarrays to generate, and subsequently analyze, the largest set
of human epidermis methylomes to date (N=108). Our results reveal a wide range of
specific but quantitatively low DNA methylation differences between young and old
epidermis. We did not find an age-related global trend towards hypomethylation as
previously described, but only a robust and highly significant hypermethylation of CpG
islands in old samples. Further identification of the gradual DNA methylation changes
occurring throughout skin aging led us to develop a highly accurate age prediction tool.
A closer look at the most variable probes showed that these stronger methylation
changes take place step-wise, in well-defined time points during the lifetime. Finally, our
data also indicate that old skin methylomes display a reduced DNA methylation
patterning, together with an increased heterogeneity. Overall, our work provides a
comprehensive outlook of the skin aging process from the viewpoint of DNA
methylation.
43
PostDoc Retreat 2015
P3.18 - Rattay, Kristin
Promiscuous gene expression in mTECs is a highly coordinated and evolutionary
conserved process
Kristin Rattay and Bruno Kyewski
Division of Developmental Immunology, Tumor Immunology Program, German Cancer
Research Center, Heidelberg, Germany.
Promiscuous expression of self-antigens in medullary thymic epithelial cells (mTECs) is
essential for tolerance imposition in the thymus. The molecular regulation of ectopic
expression of this plethora of tissue-restricted antigens (TRAs) is still poorly understood.
Promiscuous gene expression (pGE) is characterized on the one hand by inclusion of a
broad range of TRAs and on the other hand by its mosaic patterns, whereby each
antigen is only expressed in 1-3% of mTECs at a given point in time. This mosaic
pattern at the single cell level faithfully adds up to the full repertoire of self-antigens at
the population level. It remains still unclear how and when these mTEC-specific pGE
patterns become established in the first place, how they are maintained along mTEC
differentiation and to which extent stochastic and/or deterministic principles apply. The
transcriptional heterogeneity of mTECs precludes analysis of these issues at the
population level hence we reduced this complexity to the level of mTEC subsets
expressing a particular TRA. Such TRA-selected co-expression groups represented
minor fractions of the mouse mTEC compartment, showed various degrees of mutual
overlap, mapped to different stages of mTEC development and features were
conserved between mouse and human. Applying an unbiased single cell sequencing
approach, we extended these findings to show that the mouse mTEC population
represents a composite of multiple co-expression groups. These results document that
pGE is an evolutionary conserved and highly regulated rather than a stochastic process.
44
PostDoc Retreat 2015
P3.19 - Pouyanfard, Somayeh
Improvement of the Immunogenicity of Thioredoxin-L2 Peptide as a Prophylactic
Cervical Cancer Vaccine using the IMX313-T Antigen Re-engineering Platform.
Somayeh Pouyanfard1, Angelo Bolchi2, Davide Cavazzini2, Elena Canali2, Gloria
Spagnoli2, Simone Ottonello2, Martin Muller1
1
German Cancer Research Center, Heidelberg, Germany.
Department of Life Sciences, Biochemistry and Molecular Biology Unit, University of
Parma, Parma, Italy.
2
Cervical cancer is women’s second most frequent cancer worldwide, two-thirds of which
occur in less developed countries. Certain types of HPV, referred to as high-risk types
are the etiological agents of this disease.
Two prophylactic HPV vaccines are now available in market. Both are based on VLPs
assembled from the major capsid protein L1. Gardasil and Cervarix® have proven safe
and nearly 100% effective in protecting against the HPV types from which the L1-VLPs
are derived but they have limited cross protective capacity, expensive to manufacture
and distribute especially in developing countries.
On the other hand, the N terminal region of L2 proteins contains epitopes which are
able to induce cross neutralizing antibodies but the L2 derived peptides are poorly
immunogenic. Our department has shown that application of three copies of amino acid
20-38 derived from L2 protein of HPV16 fused to thioredoxin from Pyrococcus furiosus,
conferred strong immunogenicity to the peptide and induced neutralizing antibodies
against homologous HPV type 16 and cross neutralizing antibodies against
heterologous HPV types 18, 45 and 58 in mice. In order to further improve
immunogenicity of Trx-L2-based HPV vaccine, one interesting strategy could be
bringing antigen in a conformational and repetitive structure which is well suited for
multivalent engagement and signaling through B-cell receptors. Along with this line, my
research is focused on employment of the oligomerization domain of C4-binding protein
to the Trx-L2 protein in order to enhance the vaccine immunogenicity. A major
advantage of the proposed vaccine platform is cost-effective production in bacteria
compared to that of highly multivalent VLP vaccines produced in yeast or insect cells.
45
PostDoc Retreat 2015
P3.20 - Reuter, Antje
As I am working as scientific project manager and do not have a running lab project I
will not present a scientific poster during the retreat, but represent the PDN.
Nevertheless I would like to take the chance of this abstract to inform you about our
division “Virus-Associated Carcinogenesis”. If you are interested in more detail to our
work, I would be pleased to answer questions or taking suggestions.
Liver cancer is a leading cause of cancer-related deaths and to a large extent
associated with viral infections worldwide. Approximately 75% of all patients suffering
from liver cancer are infected with the hepatitis B virus (HBV) or hepatitis C virus (HCV).
Innovative therapies and diagnostics are based on the understanding of the underlying
processes, which lead to chronic viral-induced hepatitis and causing the formation of
hepatocellular carcinoma in the long term. The cellular changes are thereby triggered
not only directly from viral proteins, but also induced by the immune response.
Accordingly, the work of our department focus on analysis of the molecular and cellular
mechanisms which are relevant for the chronicity of HBV and HCV infection and the
development of associated HBV and HCV-associated liver cancer. Currently the
following areas are analyzed in individual projects in our three working groups headed
by Prof. Ralf Bartenschlager, Dr. Marco Binder and Dr. Bruno Galy:
• Replication dynamics of HCV in diverse cell culture models
• Identification of new factors in the RIG-I / IRF3 pathway
• Role of iron-regulatory networks in the infection and inflammation-induced tumor
formation
• Development of new in vitro and in vivo models for HCV and HBV individual infection
or co-infections or viral gene expression
46
PostDoc Retreat 2015
Matched Expertise Exchange
First Name
Last Name
Round
Michael
Murat
Ofure
Kristin
Ann-Christin
Magalie
Eva
Daniel
Manuel
Roberta
Yi
Christian
Mona
Antje
Konstantina
Mikolaj
Yuanyuan
Petros
Florian
Somayeh
Heiko
Fletcher
Iskar
Obazee
Rattay
Gaupel
Géraldy
Nievergall
Pastor-Flores
Rodriguez
Scognamiglio
Sun
Breunig
Malz
Reuter
Rowald
Slabicki
Chen
Christopoulos
Neff
Pouyanfard
Weyd
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
Table
T1-Bioinformatics/ Modelling
Experience
in the field
x
x
x
x
T2-Cell Biology/Imaging/ Protein
interactions
x
x
x
x
x
T3-Genomics/Genetic Engineering
x
x
x
T4-Immunology
x
x
47
PostDoc Retreat 2015
Matched Expertise Exchange
First Name
Last Name
Christian
Magalie
Murat
Mona
Daniel
Roberta
Mikolaj
Michael
Eva
Ofure
Manuel
Petros
Ann-Christin
Somayeh
Kristin
Antje
Yuanyuan
Florian
Konstantina
Yi
Heiko
Breunig
Géraldy
Iskar
Malz
Pastor-Flores
Scognamiglio
Slabicki
Fletcher
Nievergall
Obazee
Rodriguez
Christopoulos
Gaupel
Pouyanfard
Rattay
Reuter
Chen
Neff
Rowald
Sun
Weyd
48
Round
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
Table
T5-Drug discovery/(High
Throughput) Biological assays
Experience
in the field
x
x
x
x
x
T6-Epigenetics
x
T4-Immunology
x
T7-Tumor Models
x
x
x
PostDoc Retreat 2015
List of Participants
Last Name
Abassi
Barah
Berdiel Acer
Breunig
Chen
Christopoulos
Costa
First Name
Yasmin
Pankaj
Mireia
Christian
Yuanyuan
Petros
Barbara
Engeland
Fletcher
Christine
Michael
Fröhlich
Gaupel
Géraldy
González-Valliinas
Iskar
Jing
Kovaleva
Kumar
Malz
Neff
Nievergall
Obazee
Pastor-Flores
Pouyanfard
Rajasekharan
Rattay
Reuter
Rodriguez
Rowald
Martina
Ann-Christin
Magalie
Margarita
Murat
Hua
Valentina
Abhishek
Mona
Florian
Eva
Ofure
Daniel
Somayeh
Sreejith
Kristin
Antje
Manuel
Konstantina
Email
y.abassi@dkfz-heidelberg.de
barah.pankaj@gmail.com
m.berdiel@dkfz-heidelberg.de
c.breunig@dkfz.de
yuanyuan.chen@dkfz.de
p.christopoulos@dkfz.de
barbaracosta1978@gmail.com
christine.engeland@nctheidelberg.de
m.fletcher@dkfz-heidelberg.de
m.froehlich@dkfzheidelberg.de
a.gaupel@dkfz.de
m.geraldy@dkfz.de
margagvg@hotmail.com
m.iskar@dkfz-heidelberg.de
h.jing@dkfz-heidelberg.de
v.kovaleva@dkfz.de
a.kumar@dkfz.de
m.malz@dkfz.de
f.neff@dkfz-heidelberg.de
e.nievergall@dkfz.de
o.obazee@dkfz.de
d.pastor-flores@dkfz.de
s.pouyanfard@dkfz.de
s.rajasekharan@dkfz.de
k.rattay@dkfz.de
a.reuter@dkfz.de
m.rodriguez@dkfz.de
k.rowald@dkfz-heidelberg.de
Affiliation
DKFZ
DKFZ
DKFZ
DKFZ
DKFZ
DKFZ
DKFZ
Pg. no.
39
41
22
25
37
NCT
DKFZ
33
23
DKFZ
DKFZ
DKFZ
DKFZ
DKFZ
DKTK
DKTK
DKFZ
DKFZ
DKTK
DKFZ
DKFZ
DKFZ
DKFZ
DKFZ
DKFZ
DKFZ
DKFZ
DKFZ
42
35
32
43
17
44
20
21
31
38
45
46
49
48
50
47
24
49
PostDoc Retreat 2015
List of Participants
Last Name
Schneller
Schuster
Scognamiglio
Seidel
Slabicki
Sun
tang
Weyd
Wu
50
First Name
Doris
Christian
Roberta
Philipp
Mikolaj
Yi
yan
Heiko
Huizi
Email
d.schneller@dkfz.de
Christian.schuster@dkfz.de
r.scognamiglio@dkfz.de
p.seidel@dkfz.de
mikolaj.slabicki@nct-heidelberg.de
Yi.Sun@dkfz.de
y.tang@dkfz.de
h.weyd@dkfz.de
huizi.wu@dkfz.de
Affiliation
DKFZ
DKFZ
DKFZ
NCT
NCT
DKFZ
DKFZ
DKFZ
DKFZ
Pg. no.
36
19
30
18
16
15
34
PostDoc Retreat 2015
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51
POSTDOC RETREAT 2015 - PROGRAM
Day 2 – November 6th, Friday
Day 1 – November 5th, Thursday
10:00
Registration
08:00
Breakfast
10:15
Welcome
09:00
Oral presentations - Session 3
11:00
Oral presentations - Session 1
10:20
Coffee break / Poster session 2
12:30
Lunch
11:15
Guest Speaker - Dr. Susan Kentner
14:00
Guest Speaker - Dr. Aidan Budd
12:30
Lunch
15:15
Coffee break / Poster session 1
13:30
Matched Expertise Exchange
16:15
Oral presentations - Session 2
14:30
Coffee break / Poster session 3
17:15
Round Table Discussion
15:30
Closing remarks, prize ceremony and departure
19:00
Dinner
20:30
Evening program