What is your research focus and research expertise?
In a nutshell, my research focus and expertise are macrophages, studying the role of these cells in the onset of diseases and how these cells can be used in modern immunotherapies. 

What are your main research questions?
My research is divided into four parts, each connected in order to retrieve knowledge from patients, which is ultimately used to develop new therapies in the framework of immune cells in particular macrophages. It all starts with patients and trying to gain new insights into the role of macrophages in these patients. We are particularly interested in “what goes wrong” and/or how macrophages behave in a certain disease condition. Macrophages are immune cells that are located in almost every type of tissue. Given their high plasticity, which means they can adopt certain stages of activation, they are crucial in the onset and progression of various diseases, including cancer. We use these unique functions of macrophages and aim to restore or enhance their function in order to assist the endogenous immune system to fight disease conditions. In the context of malignancies, this can be applied manifold, using the cells as cellular immunotherapies to fight solid malignancies, to avoid side effects, or to treat infections which may occur during the anti-cancer treatment and which may be hard to treat. In other words, macrophages are universal cells and our understanding of these cells as a therapeutic target is constantly improving. We aim to provide new tools and to develop new therapies. For this, we use the technology of induced pluripotent stem cells, in short iPSCs. We developed a technique which allows for the continuous and scalable production of immune cells such as macrophages, but also NK cells, in industry compatible bioreactors. These cells are used to develop new immunotherapies and most recently also to establish new bioassays. In fact, iPSC-derived immune cells are highly standardized, which means that these cells always come from the same donor, having little to no variations in the activity and behavior of cells. This standardized cell type now allows for the establishment of new bioassays, which hasn't been possible with classical donor-derived immune cells. We aim to use macrophages and screen for drugs or compounds, which have an impact on the polarization of macrophages within the tumor. The tumor microenvironment is very much instructive in polarizing macrophages towards an anti-inflammatory, more pro-tumoral phenotype. We aim to find drugs that are able to revert this phenotype in vivo. We are currently exploring novel tumor diagnostics, as some type of tumors are diagnosed only at a late stage, which has a negative impact on treatment outcome. Using our standardized macrophages, we are exploring a new diagnostic tool, which we hope will contribute to improving cancer diagnostics. 

What are findings you are excited about?
The combination of human iPSC research and macrophage biology is unique and can be applied in a huge variety of diseases. Using this combo to gain insights into patients, to develop new therapies, and novel drugs excites me every day. If you understand the system and if you have a deep understanding in the technology platform, the possibilities to apply them are endless. As an example, you can genetically engineer iPSCs to express chimeric antigen receptors (CARs) very much known in the T cell field. This engineered iPSCs can then be subjected to industry compatible bioreactors to produce macrophages, NK cells and other cell types. Given the broad function of macrophages, you may think of alternative strategies to interfere in the polarization of cells, all aimed at manipulating the disease in vivo, improving patient outcome. So you see, the possibilities for applying this technique are broad, which is wonderful for not only for research, but also for patients. 

What kind of techniques and methods do you use for your research?
We frequently apply human iPSCs, a technology first introduced in 2006 and awarded with the Nobel Prize in 2012 (the fastest Nobel Prize ever, by the way!). We use human iPSCs to differentiate these cells into macrophages (and other immune cells). These cells are then used in the lab to elaborate new therapies and/or drugs. We also have scalable differentiation systems, which are used to test new bioprocess parameters, which are needed to manufacture cells at clinical scale. 

Why did you choose your research focus? Why did you shift towards cancer research?
I came to know the hematopoietic system and stem cells in general at the time as a Master of Science student at Yale University School of Medicine in the lab or Richard Flavell. Given my background as a PhD (doing basic research), I always wanted to translate my findings back to directly helping patients and that was the reason why I was working on macrophages and a rare lung disease in the department of pediatric pneumology, allergology and neonatology here at MHH in 2012 (first year of my PostDoc). I learned so much about macrophages and the possibilities that I continued my research on macrophages and iPSCs, expanding into infectious diseases and most recently into cancer. To be honest, I have little knowledge in oncology, but I have a long-standing and profound expertise in macrophages. I have seen the potential of T and NK cells to combat malignancies and given my background, I knew that tumor associated macrophages especially in solid malignancies are one important cellular player. MHH and also the UMG have synergies and excellent scientists and MDs specialized in oncology that are present at both sites. Regularly, I am in exchange with a variety of specialists, whose expertise is then combined to enter research areas and to explore novel therapies. To my understanding, you have to work in an interdisciplinary team, as individuals cannot capture the complexity of a certain tumor condition. As a side note and homage to my mother. She passed away very recently due to pancreatic ductal adenocarcinoma (PDAC) and I learned a lot in the past 24 months about this disease. My research focus will not change and will remain at macrophages, iPSCs and infectious diseases. However, my ambition to approach oncologists and other scientists to form a syndicate and research collaborations has and will increase to elaborate new therapies in the oncology field. 

How did you become a researcher/scientist?
My CV is a bit uncommon as I first finished secondary school (Realschule) and then did an apprenticeship as a biology research assistant (BTA). After finishing, I went back to school to receive my A-level before going to university to receive my B.Sc. and M.Sc. degree from MHH. After doing my PhD also at MHH, I did post-doctoral work at MHH, the Max-Planck Institute for Biomedicine in Münster, and the Cincinnati Childrens Hospital Medical Center (CCHMC). During that time, I was trained on translational science in the framework of macrophages in health and diseases, working with collaboration partners on cell & gene therapy approaches for the lung and beyond. 

Which institutions/organizations shaped your work/career? 
Well, most importantly of course Hannover Medical School, as I spent most of my career in the Institute of Experimental Hematology. However, also my time at Yale University and Cincinnati Childrens Hospital has been very much crucial for my career. While the time at Yale introduced me to the field of hematology and stem cells, the time at CCHMC and the supervision by Prof. Bruce Trapnell have been inspired to further look into the clinical translation of science. Indeed, Bruce is an MD with passion for wet-lab work but also patient care and I was fascinated about this dual work. I realized the importance to bridge the research back to patients, moving along this line and to bridge macrophage-related research to patients. 
How can your translational research activities benefit from the CCC-N research structure?
As mentioned before, the development of novel tools for diagnostics and therapy is only possible if various disciplines work together. Oncology is quite a complex field and a broad expertise is needed to pioneer novel therapeutic concepts. Given my expertise in macrophages, immune cell farming, and gene therapy/ genome engineering, the CCC-N offers complementary expertise, which ranges from scientific to clinical expertise in the field of oncology. Pre-clinical experimental models, methods to test your idea and patient material are only few examples, which are needed to successfully perform one’s research. I am pleased to have this network within the CCC-N but also the MHH to elaborate new therapies. I am convinced about the value of the CCC-N. However, a more stringent interaction and funding scheme would unleash the full potential of the CCC-N in the future. This being said, I would like thank all partners and collaborators, which are dedicated to bridge iPSC-derived immune cells into patients. 

Can you tell us a little about your working group? 
Sure, the group started in 2015 and was initially funded by the Cluster-of-Excellence REBIRTH, focusing on rare diseases of the lung. The lab has grown substantially in the past years and receives funding from a variety of funding organizations. The lab is member of the German Center for Lung Research and the current Cluster-of-Excellence RESIST, in which we aim to further understand host susceptibility to pathogens establishing new immunotherapies to fight infectious diseases. Although a different discipline, most of the knowledge we derive from this work also feeds into work related to oncology, since the enhancement and/or targeting of macrophages is used to fight malignancies. 

How many people work in your lab?
As of now, the lab has approx. 15 members, which are all dedicated to iPSC, immune cell farming and immunotherapeutic projects. The understanding of how human immune cells (e.g. macrophages) originate directly feeds into protocols and techniques for the scalable production of cells. Genome engineering approaches and people in the lab with expertise in bioassays to screen for drugs, which can (re)polarize macrophages, are working together with experts in cell manufacturing. 

What is their level of education / career stage? 
We have scientists in the lab from all career levels. It starts with a student enrolled in the “FWJ; Freiwilliges Wissenschaftliches Jahr”, who is working on strategies to manipulate macrophages in vivo. Regularly, we do have Master students in the lab, who are working on new macrophage and immune cell farming strategies together with either PhD students or PostDocs. The projects of the PhD students and PostDocs are all dedicated to the use of macrophages and other immune cells in the frame of diseases or to understand the role of macrophages in the onset and progression of defined disease entities. Our lab also welcomes MD students, who are enrolled in the HBRS at MHH and which are working with patient iPSC material. One important backbone of the group are our three technicians, who are of utmost importance for the lab and part of basically every project. 

What is the biggest challenge in cancer research?
In a nutshell: the variety of malignancies and the individual complexity of the respective tumor.