Dr. Michel Heger

Group: Dr. Sven Borchmann, University Hospital Cologne, Medical Clinic I

Project:

Molecular classification and dynamic prognostication of aggressive B-cell
malignancies by circulating tumor DNA sequencing
 

One Fellow…Two Questions

Michel, what was your motivation of becoming an EKFS fellow?

Aggressive B-cell malignancies display a large distribution of outcomes. While some patients literally walk through chemoimmunotherapy in an outpatient setting, others fight with relapsed/refractory disease for months or years and eventually succumb to it. Due to these inequalities, improving overall treatment strategies has become quite challenging.
My motivation is to learn more about biological factors that contribute to adverse outcomes and utilize these to stratify patients according to their individual risk.
Being an EKFS fellow offers the possibility to be part of an innovative pre-clinical surrounding with broad experience in translational research regarding biological risk stratification.  

 

Where lie your clinical and scientific interests?

Within the past years of my clinical training, I developed a strong interest in hematologic malignancies, especially aggressive lymphomas as well as intensive care medicine. Herein, I gained a robust experience in the treatment of relapsed/refractory aggressive B-cell malignancies and severe side effects of novel therapeutic strategies.

Several novel therapeutic approaches have been developed and introduced into clinical care within the past years. However, it remains challenging to accurately predict response and prognosis. Thus, I gained a specific interest in novel techniques aiming to detect high-risk profiles and to predict outcomes dynamically. I want to focus my scientific research on genetic profiling, risk assessment and dynamic therapy monitoring in aggressive B-cell malignancies. While most current sequencing strategies for detailed genotyping of lymphoid malignancies are based on tissue samples, liquid biopsies provide a less invasive approach without lack of precision. In order to move liquid biopsy-based genotyping further towards clinical feasibility, I would like to optimize sensitivity and specificity of currently available technology. I believe that accurate prognostication represents a key step towards the desire of improving therapeutic strategies.
Besides pre-clinical and translational research, I will continue several clinical projects and coordination of clinical trials that are ongoing.
Overall, I feel that it is essential to meticulously review the risk-to-benefit ratio of novel therapeutic approaches in a rapidly growing environment.

 


Dr. Noëlle Sieg

Group: Prof. Dr. Hamid Kashkar, Institute for Molecular Immunology

Project:

Role of caspases in Venetoclax induced cell death of B cell malignancies

One Fellow…Two Questions

Noëlle, what was your motivation of becoming an EKFS fellow?

After two years of clinical education in the field of oncology and intensive-care medicine as well as gaining experience in clinical lymphoma research I now intend to focus on molecular mechanisms of malignant lymphoma pathogenesis.
Being an EKFS fellow is giving me the opportunity to learn innovative technologies and be a part of an interdisciplinary research group that has already largely contributed to the existing knowledge of BCL-2 family members and their role in B-cell malignancies.
However, a better understanding of the role of caspases in lymphomagenesis might ultimately reveal new therapeutic approaches and could improve the treatment of patients suffering from malignant lymphoma. 
In the future, I would like to do both: work as a clinician and contribute to cancer research.

 

Where lie your clinical and scientific interests?

Since the beginning of my medical studies, I was fascinated by the emerging treatment options coming up in the field of oncology.
During my clinical education I got insight into the treatment of patients with therapy-refractory malignant lymphomas as well as innovative therapeutic options such as CAR-T-cells. Being particularly interested in the field of high-grade lymphomas I participated in clinical projects involving CART-T-cell therapy and central nervous system lymphoma as part of the Cologne Lymphoma Working Group.
In my clinical work I was confronted with several patients suffering from therapy refractory malignant lymphomas accompanied with a poor prognosis, awaking my interest in a deeper understanding of those diseases in order to develop new treatment strategies.
Resistance to apoptosis being a general hallmark of cancer and resistance to the mitochondrial apoptosis pathway being particularly important for lymphoma pathogenesis I got interested in the work of Prof. Hamid Kashkar and his lab.
While the role of BCL-2 family members in lymphoma biology has been extensively studied, the role of caspases in lymphomagenesis is by far less well defined. I very much appreciate the opportunity to contribute to that field of research which in the future might help to treat patients that suffer from malignant lymphoma.

 


Dr. Sebastian Michels

Group: Prof. Dr. Axel Hillmer, Genomische Pathologie

Project:

Dissecting the evolutionary trajectory of resistance and residual disease in EGFR-mutant lung cancer on the single-cell level

 

One Fellow...Two Questions

Sebastian, what was your motivation of becoming an EKFS fellow?

Individual encounters at the clinics and the commitment of patient advocacy groups, such as the ROS1onders, are driving my motivation to improve the prognosis of cancer patients. I am convinced that the integration of pre‐clinical and clinical discovery is essential to foster advances in cancer treatment. The rapid translation of pre‐clinical findings into patient care and vice versa, is only possible through a tight interaction between clinics and clinical and pre‐clinical research. As a clinician and researcher, I aim to fulfil these requirements.

The EKFS postgraduate fellowship program allows me to join the excellent local pre‐clinical structures and to add clinical incentives to the field of lung cancer research.

 

Where lie your clinical and scientific interests?

Since my MD student fellowship at the sarcoma research group of Wolfgang Hartmann (Institute of Pathology, University Hospital of Bonn), I have been fascinated by cancer biology and treatment and quickly discovered, that I wanted to become medical oncologist.

As a clinician scientist at the Lung Cancer Group Cologne, I learned that the biggest medical need was the treatment of acquired resistance to targeted treatments and the understanding of the driving mechanisms. Inspired by the fruitful interaction with the Institute of Pathology and other research groups, I decided to join the genomics research group of Axel Hillmer in January 2020.

The aim of my research there, is to understand the mechanisms that drive genomic and transcriptomic heterogeneity in acquired resistance in lung cancer and to derive potential treatments. In particular, I seek to understand why in the beginning distinct mechanisms of resistance are selected for by the same treatment and why finally increasing intra‐tumor heterogeneity limits the efficacy of targeted treatments in the clinical setting. Therefore, I first focused on the understanding of the biology of drug‐tolerant persister cells and pre‐existing resistant subclones using single cell transcriptomics in primary cell lines and patient‐derived cell models.

Besides this, I will continue to coordinate ongoing and future clinical projects, such as a phase II investigator‐initiated trial, that investigates the role of a new bispecific antibody in the treatment of resistance to EGFR-targeted drugs.

 


Dr. Anna-Maria Hellmann

Group: Prof. Dr. Matthias Fischer, Experimental pediatric oncology

 

Project:

Unraveling the molecular pathogenesis of neuroblastoma using novel genetically engineered mouse models

 

One Fellow...Two Questions...

Anna-Maria, what was your motivation of becoming an EKFS fellow?

As a physician scientist, it is my firm belief that translational research is of upmost importance to the advancement of patients’ treatment in oncology.
The EKFS program is a powerful tool, that supports me as young clinician, by providing the opportunity to focus on my scientific career and to strengthen my scientific profile.The EKFS invests in the advancement of my research and professional development by providing protected research time, as well as excellent scientific education. Through its interdisciplinary design and close contact with other colleagues, it will broaden my scientific horizon and help me to work on my project successfully.
I am excited to be an EKFS fellow and to contribute to the challenge of decoding new mechanisms in cancer pathogenesis to improve cancer therapy in the future.

 

Where lie your clinical and scientific interests?

I have always been interested in the deeper understanding of molecular mechanisms in cancer and fascinated by the rapid progress in this field in recent years. Pediatric oncology offers the combination of taking good clinical care of the young patients and personally accompanying them and their families for a long period of time with ongoing scientific progress in the field. Unfortunately, treatment still remains challenging in a considerable set of our patients, who may go through multiple lines of treatment with limited chances of long-time survival. I am particularly interested in the pathogenesis of neuroblastoma, which is characterized by highly heterogenous clinical courses.
The focus of my project is to unravel new mechanisms of high-risk neuroblastoma pathogenesis, which contribute to this heterogeneity. Identification of new driver mutations would enable a deeper understanding of tumorigenesis and might enable new therapeutical approaches for this disease.

 

 


Dr. Christoph Arolt

Group: Prof. Dr. Axel Hilmer, Genomische Pathologie

 

Project:

Spatial transcriptomics of esophageal adenocarcinomas: understanding the role of tumor architecture for stroma activity and treatment resistance

One Fellow...Two Questions...

Christoph, what was your motivation of becoming an EKFS fellow?

After three years of clinical training and simultaneous research, I plan to commit more time to projects that provide deeper insights into mechanisms of TME.
Also, becoming acquainted to novel, elaborate technologies will require a stronger focus on research for a defined period of time. The EKFS provides both the freedom to achieve these goals and a distinguished scientific framework.

I am now looking forward to be part of an interdisciplinary group that is focused on ambitious oncologic results.

Where lie your clinical and scientific interests?

Having the opportunity to visualize, analyze and understand the architecture and driver mechanisms of tumors has been the major reason to start my training in pathology.
Clinically, I followed the path towards the complex subtyping of salivary gland carcinomas (SGC) both morphologically and through molecular testing.
Recently, for the first time, we described the extracellular matrix composition of SGC using Nanostring and IHC/ISH. More recently, my focus broadened towards a training in GI pathology.
Scientifically, my overarching interest is to identify the complex interactions of cells within the tissue microenvironment (TME) of carcinomas.

As a next step, I would like to extend my field of research towards the TME of esophageal adenocarcinomas.
I am convinced that we should invest in understanding the spacial dimension to highly-plexed genetic and proteomic analysis which will fuel the discovery of novel cellular interactions.