Groups at the German Cancer Research Center (DKFZ) and Heidelberg University Hospital (UKHD) that are involved with activities at the NCT Heidelberg and offer to host an HSO² Fellow in the current call are listed below. The list of hosting groups will be regularly updated during the call.
Potential Hosting Groups
We focus on developing and applying bioinformatics and AI technology to high-dimensional data, in particular from sequencing methods in cancer genomics and epigenomics in precision oncology. We are part of large international collaborative efforts to characterize somatic alterations in cancer, e.g. the ICGC-PCAWG initiative (pan-cancer analysis of whole genomes). Additional topics comprise the analysis of tumor immune microenvironments by computational analysis of single-cell sequencing data.
A potential topic will address the study of replicative immortality in cancer, which is conferred by telomere maintenance mechanisms. These can be studied from sequencing data by tools like TelomereHunter, which has been developed in our group. The project will use the data from ca. 3000 cancer genomes, epigenomes and transcriptomes from the NCT-MASTER trial to develop novel machine learning techniques to improve patient care. The specific goals of the project will be defined together with the successful applicant.
DermatoOncology and Medical Oncology
Within different tumor entities efficacy of checkpoint inhibitor therapy in forms of PD-1/PD-L1 blockade of CTLA-4 blockade varies significantly. Whereas in general a high efficacy is observed in metastatic melanoma, a smaller percentage of patients shows a benefit in many other entities such as esophagogastric cancer, urothelial cancer or head and neck cancer. As a result, many patients still fail to respond to checkpoint inhibition. Mechanisms of response or resistance are only partially understood, in addition the predictive value of biomarkers such as PD-L1 expression differs significantly between different tumor entities. Previous work including our own demonstrates that the intra-tumoral immune infiltrate plays an important role for responsiveness, i.e. patients showing stronger tumor infiltration by PD-1 expressing tumor infiltrating lymphocytes (TIL), B cells, regulatory T cells (Treg) and M1 macrophages seem to benefit more from PD-1 blockage (BMBF junior consortium TIL-REP). TCR analyses of melanoma metastases in patients receiving immune checkpoint blocker treatment revealed that there was no significant difference in the TCR repertoire concerning richness and clonality before treatment. Under treatment responding patients revealed a richer repertoire in the tumor with no significant changes in the peripheral blood. The expression of other immune checkpoints such as LAG-3 (lymphocyte-activation gene 3) and TIM-3 (T-cell immunoglobulin and mucin-domain containing-3) might contribute to treatment resistance and are investigated within a DFG-supported PhD program (RTG 2099 Hallmarks of Skin Cancer). Furthermore, the mutational load, including the microsatellite status as well as the presence of viral pathogens (including EBV and HPV) are clearly associated with efficacy of checkpoint inhibition.
The current project focuses on a cross-entity analysis of immunological mechanisms and predictive biomarkers for sensitivity and resistance to checkpoint blockade. As two pilot entities, tumor specimens from patients with melanoma and esophagogastric cancer will be analyzed, including immunohistochemical studies on immune cell infiltrations, checkpoint expression and other possible markers, transcriptomic analysis e.g. on inflammatory/b-catenin pathways and serum biomarkers such as soluble immune checkpoints and composition of peripheral blood immune cells. With this done for melanoma in part already, the comparison with esophagogastric cancer tumor samples might give new insights in important differences in immunotherapy responsiveness. Moreover, promising combinations can be tested in an ex vivo setting.
Institute of Medical Informatics
Principal investigator: Prof. Dr. Martin Dugas
More information: Institute of Medical Informatic, UKHD
Research topics of the Institute of Medical Informatics (IMI) @UKHD
- Medical Information Systems (specifically integrated systems for patient care and research)
- Medical Data Models
- Clinical Decision Support
IMI is developing and maintaining the MDM-Portal, Europe's largest collection of medical data models. More than 1/3 of MDM contents is from the domain of oncology. There is specific expertise regarding medical semantics (UMLS, SNOMED, LOINC etc.).
High-volume and high-quality clinical data sets are key success factors for clinical decision support and artificial intelligence projects in medicine. State-of-the-Art electronic data capture (EDC) systems are designed and implemented at IMI using model-driven software development. The Medical Data Integration Center (MeDIC) of the HiGHmed Consortium is part of IMI. MeDIC is responsible for the full range of access to patient data for research purposes at the UKHD.
A fellowship at IMI provides unique opportunities to acquire skills for digital oncology in the field of medical informatics.
Medical Physics in Radiation Oncology
Principal investigator: Prof. Dr. Oliver Jäkel
More information: Medical Physics in Radiation Oncology, DKFZ
We focus on research in image guided, adaptive radiotherapy (ART), concentrating on optimization of efficient, AI-based workflows for ART and novel optimization strategies. In 2022 we will initiate a novel treatment machine (ETHOS) for fast CBCT-based ART at DKFZ and start several projects with our clinical partners: a multi-centric, translational oncology project, funded by DKH, on ART for locally advanced lung cancer, comparing the potential of MR and CBCT guidance; a feasibility trail will investigate ART for cervical carcinoma and we will investigate sim-and-treat at the ETHOS (CBCT-based treatment planning). We also contribute to projects on MR-guided particle therapy and the MR-Linac at the University hospital and continue to explore the radiobiology of ion beams at HIT. We envisage a strong clinical contribution of a clinician scientist in the following areas:
The group Computational Patient Models is developing digital patient twins for RT, meaning the creation of digital copies to stand in as proxies for computerized patient-tailored plan optimizers and as treatment monitors for accumulated dose and image-extracted early effect predictors.
Potential projects involve:
- DL (deep learning)-driven, but guideline conformal target volume delineation
- ML (machine learning)-driven, but motion-insensitive MR-to-CT image translators
- ML (machine learning)-driven 4D motion predictors guided by 2D cine imaging
The group Radiotherapy Optimization investigates new methods to optimize RT treatment plans, including incorporation of uncertainty or outcome models into classical planning, as well as novel treatment strategies like mixed-beam therapy.
- Towards clinically acceptable jointly optimized mixed-modality treatments
- Improving ML-based treatment outcome models addressing the bias from treatment plan design
The group Applied Medical Radiation Physics performs radiobiological studies in animals to investigate the differential effectiveness of ions compared to photons in normal tissues and tumors. This includes the experimental determination of RBE for comparison with model predictions and diagnostic imaging studies as well as histological and molecular analysis of tissue samples obtained from the irradiation experiments.
Potential Projects are related to the investigation of:
- late effects in rat spinal cord after photon, proton and ion irradiations
- response of hypoxic and normoxic tumors after photon, proton and ion irradiations.
Principal investigator: Prof. Dr. Dr. Felix Sahm, MBA
More information: Molecular Neuropathology, UKHD
Novel biomarkers for diagnosis, prognostic stratification, and targeted therapy of brain tumors are the focus of the Division Molecular Neuropathology.
At the interface of research and diagnostic application in our routine services, we are exceptionally positioned to translate the findings of our projects into patient care.
Our approach has resulted in a variety of novel biomarkers and diagnostic tools that were immediately implemented into international guidelines (e.g. WHO classification of brain tumors) and contributed to the novel standard of brain tumor sample work-up. Examples of our work comprise the identification of prognostic subgroups of meningioma (Sahm et al., Lancet Oncology 2017), a new grading approach to meningioma (Maas et al, JCO 2021), our joint work on delineating new subtypes of ependymoma (Zheng et al., Cancer Discovery 2021), or the studies on new tumor types and subtypes based on DNA methylation and pathognomonic gene fusions (Sievers et al., ANP 2018, 2019, 2020 and 2021, Suwala et al., ANP 2021).
For these projects, we can leverage an unmatched archive of clinically and molecularly annotated samples, and modern in-house technology including full setup for high-throughput bulk, single-cell and long-read (nanopore) sequencing. Our diverse team of physicians (many in or with experience in physician-scientist programs), bioinformaticians, biologists, MD and PhD students is matched with a strong network of collaboration partners in adult and paediatric neuro-oncology, neurosurgery, neuroradiology, other associated clinical disciplines and bioinformatics in Heidelberg and internationally.
Current projects are devised to accelerate the diagnostic workflow by third-generation sequencing, increase the precision and value of neuropathological work-up for immunotherapy by setting-up regular single-cell sequencing of diagnostic samples, and identify the growth trajectories of glioma and meningioma back to the cell of origin.
Oral Cavity Cancer
Principal investigator: Prof. Dr. Dr. Christian Freudlsperger, Department of Oral and Maxillofacial Surgery, University Hospital Heidelberg (email@example.com), Prof. Dr. Jochen Heß, Section Experimental and Translational Head and Neck Oncology
More information: Section Experimental and Translational Head and Neck Oncology
The Working group “Oral Cavity Cancer” focusses on the investigation of prognostic markers for oral cancers using novel techniques like digital pathology analysis of tissue samples and ex-vivo culture models in a large cohort of different surgically treated oral malignancies.
Salivary gland carcinoma (SGC) are rare tumors with an annual incidence of 0.4-2.6 / 100,000 cases worldwide. Of the histologically very diverse salivary gland carcinomas (22 known subtypes), in addition to salivary duct cancer (SDC), adenoid cystic carcinoma (ACC) and mucoepidermoid carcinoma (MEC) are the most common. Salivary gland carcinomas are usually characterized by a slow and local progression with a preferential spread along nerve tracts. Perineural tumor spread is a negative prognostic factor and associated with poor survival rates. In addition to the occurrence of local recurrences, distant metastases preferentially develop in the lungs and bones.
In view of the limited treatment options and poor prognosis for salivary gland carcinomas, there is a need to investigate targeted and personalized therapy methods using digital pathology and to analyze new, innovative therapy options such as immunomodulators or checkpoint inhibitors for salivary gland carcinomas. The investigation of immunohistochemical staining of biomarkers by means of digital pathology is an excellent method for risk stratification of patients. The clarification of possible mechanisms for resistance in relation to possible mutations or changes in the gene expression of salivary gland carcinomas can be analyzed and evaluated in detail, especially with the help of digital pathology. Another focus of this project is the analysis of tumor-associated immune cell signatures, especially since a very comprehensive and in-depth analysis is possible with the help of digital pathology. Knowledge of immunogenicity and the tumor-associated immunological milieu can support the adaptation and optimization of tumor therapies and thus the therapy response in the future.
Pediatric Glioma Research
Principle investigator: Dr. David Jones
More information: Pediatric Glioma Research, DKFZ/KiTZ
The Division of Pediatric Glioma Research at the DKFZ and KiTZ focuses on the full spectrum of research into childhood brain tumors (gliomas), from basic research (genomics and functional studies) to preclinical work in vitro and in vivo and also on translation of these findings into clinical application. The Division is also heavily involved at the interface between Big Data/Omics data generation and analysis, and the application of these into clinical setting. For example, we play a key role in coordinating international diagnostic studies for childhood cancer patients, including the INFORM and MNP2 studies.
The proposed project involves working on another such example of bringing molecular diagnostics into clinical practice, within the LOGGIC Core BioClinical Databank register study for profiling of low-grade glioma patients. This international study is recruiting childhood brain tumor patients from multiple sites globally, to offer cutting-edge molecular diagnostics based on technologies co-developed within the Division. The work will involve a close collaboration with the groups of Prof. Olaf Witt (Pediatric Oncology) and Profs. Andreas von Deimling / Felix Sahm (Neuropathology), as well as with multiple leading translational research centers across Europe. The clinician scientist will be involved in the generation, aggregation and analysis of multi-omics data from prospectively enrolled pediatric glioma patients, in order to further develop tools for enhancing diagnostic precision and to identify novel prognostic/predictive biomarkers. In this regard, the project will offer insights into the impact of comprehensive molecular profiling on individual clinical decision making, as well as a broad overview into tools and methods for analyzing and interpreting large Omics datasets. The position would suit clinician scientists with interests in pediatric oncology, molecular diagnostics and translational research, as well as those looking to work as part of a large multinational team.
Radiation Oncology - Head and Neck Tumors & Department of Oral and Maxillofacial Surgery
Principal investigator: Prof. Dr. Sebastian Adeberg, Dep. of Radiation Oncology, INF 400, 69120 Heidelberg, 06221-5635654, firstname.lastname@example.org & Prof. Dr. Dr. Christian Freudlsperger, Department of Oral and Maxillofacial Surgery, INF400, 69120 Heidelberg
More information: Head and Neck Tumors
Within the prospective NAVIGATORR trial we aim to improvement local tumor control in head-and-neck cancer (HNC) by increasing the precision of surgical resection and individualization of radiotherapy. In localized tumors, primary tumor resection with possible adjuvant (chemo)radiotherapy is still the treatment of choice. Advances in targeted therapy have greatly expanded the repertoire of medical oncology in recent years. Importantly, all of these advances are based on personalized and targeted therapies. Unfortunately, surgical oncology in the head-and-neck region has not yet shown such developments towards individualized treatment, so that the rates of safe oncological resections (clear resection margins) haven been stagnating. Despite advances in reconstructive surgery that allow the resection of head-and-neck tumors that would not have been operable 15 years ago, the basic principles of the resection margin and especially margin evaluation have remained unchanged. The technique of navigation-based tumor resection and the annotation of biopsies by titanium clip-markings or special annotation have been described, but not correlated with clinically relevant parameters.
Therefore, the NAVIGATORR trial will enroll 60 patients with HNC of the midface that will undergo navigation-based surgery. Importantly, interdisciplinary data exchange of the intraoperative navigation data between surgeons, pathologists and radiation oncologists will be established. Clear surgical margins (> 5mm) have been defined as primary endpoint.
The main task of the fellow is to manage the translational work program of the prospective NAVIGATORR trial. The first explorative objective encompasses detection of early predictors of tumor persistence and/or recurrence derived from multiparametric MRI and ct-DNA. An additional explorative analysis will focus on detection of MRI parameters that may serve as diagnostic tool of radiogenic side effects. Moreover, we aim to demonstrate an increase of ct-DNA in the peripheral blood at an early stage of clinically visible tumor relapse or even before clinically visible tumor relapse. We aim to further elucidate molecular changes of tumor cells due to treatment by processing fresh tumor specimen and compare these to the ct-DNA analyses. In particular, the behavior of patient-derived 3D-cell cultures of tumor tissue should be correlated with ct-DNA-analyses as well as clinical parameters.
Principle investigator: Prof. Dr. Jörg Heil, MHBA
More information: Senology, UKHD
We are a group of clinical trialist with focus on breast cancer diagnostics, surgery and reconstruction.
we conceptualize and perform clinical trials in all phases, from retrospective, exploratory, hypothesis-generation to multicentre confirmatory randomized trials.
We have a number of clinical scientists / trialsts in our group and are happy to welcome more motivated collegues with interest in these topics.
Translational Medical Oncology
Principal investigator: Prof. Dr. Stefan Fröhling
More information: Translational Medical Oncology, DKFZ/NCT
Our ambition is to improve the way we practice oncology towards a more rational and personalized approach. Our division, therefore, engages in all aspects of the translational research process, including one of the most comprehensive cancer molecular diagnostics programs worldwide (NCT/DKFZ/DKTK MASTER), clinically guided exploratory research projects, and – of particular relevance to prospective HSO Fellows – the implementation of innovative clinical trials. Within the NCT/DKTK MASTER program, we have analyzed more than 3,000 tumor samples by whole-exome/genome and RNA sequencing and genome-wide DNA methylation profiling and discovered previously unrecognized recurrent genetic alterations – including complex genomic, epigenomic, and transcriptomic signatures – in various tumor types (Horak et al. Cancer Discov 2021).
In several cases, we have been able to decipher the functional and mechanistic consequences of genetic alterations identified in human cancer patients and, in select cases, feed the results back into the clinic, as exemplified by our discoveries of pharmacologically tractable NRG1 rearrangements in pancreatic ductal adenocarcinoma (Heining et al. Cancer Discov 2018), genomic imprints of defective homologous recombination DNA repair (“BRCAness”) in bone and soft-tissue sarcomas (Chudasama et al. Nat Commun 2018, Gröschel et al. Nat Commun 2019), and activating ERBB2 mutations in peripheral nerve sheath tumors (Ronellenfitsch et al. J Clin Invest 2020).
The ultimate clinical goal of MASTER is to move away from assessing the therapeutic activity of targeted, molecular mechanism-based therapeutic interventions on an individual-case basis. To this end, we are working, in close collaboration with the NCT Clinical Trial Center, on a continuously growing portfolio of cross-institutional basket trials that are linked to the MASTER platform and assume that the presence of a specific molecular marker predicts response to a targeted therapy independent of tumor histology. To help realize the promise of personalized oncology based on scientific inquiry and biology-guided clinical decision making, we are seeking highly motivated candidates with a passion for applied cancer research. Specific projects are available in both focus areas, "Digital Oncology" and "Clinical Trials".