Dr. Jana Riegger-Koch

Dr. Jana Riegger-Koch is a Margarete von Wrangell-Fellow and junior group leader at the Division for Biochemistry of Joint and Connective Tissue Diseases (head: Prof. Dr. med. Rolf Brenner). Her research mainly focuses on the molecular pathomechanisms of posttraumatic osteoarthritis (PTOA).

Traumatic joint injuries are known as the main risk factor of PTOA – a special form of OA, predominantly affecting patients who are active in sports and often considerably younger than average OA patients. The pathogenetic processes include oxidative stress, (regulated) cell death, release of damage-associated molecular patterns (DAMPs) and catabolic enzymes, as well as synovial inflammation. Altogether excessive biomechanical stress and posttraumatic conditions (DAMPs, ROS, and cytokine release) result in phenotypical alterations of surviving chondrocytes. Instead of maintaining the homeostasis of the extracellular matrix and repairing the injured cartilage, dysfunctional chondrocytes promote ongoing degradation of the tissue. Although cartilage is considered as a non-regenerative tissue, there is increasing evidence of intrinsic cartilage repair by injury-responsive chondrogenic progenitor cells.

Special focus of Jana`s group is currently placed on stress-induced premature senescence as well as the contribution of complement activation products, in particular anaphylatoxins and the terminal complement complex, as potential effectors in cartilage degeneration. The projects not only aim on the clarification of the underlying pathomechanisms of PTOA but also the development of novel pharmacological and cell-based treatment strategies. To study the posttraumatic behavior and fate of surviving chondrocytes, the research group established a special human ex vivo cartilage trauma model and uses isolated human chondrocytes as well as chondrogenic progenitor cells.

Jana is funded by the DFG and is member of the CRC1149.

Foto:Elvira Eberhardt

Dr. Rebecca Halbgebauer

Dr. rer. nat. Rebecca Halbgebauer is a postdoctoral research fellow at the Institute of Clinical and Experimental Trauma Immunology (Director: Prof. Markus Huber-Lang). As a group leader of the AG Multiple Organ Dysfunction Syndrome (MODS), her research is mainly focused on organ dysfunction after traumatic injury.

Trauma remains one of the leading causes of death especially in people below the age of 45, with more than 5 million deaths worldwide every year. Around 20% of ICU patients face multiple organ dysfunction and failure during the clinical course, resulting in substantial morbidity. This clinical picture can be caused by excessive inflammation, leukocyte tissue recruitment, and breakdown of intercellular barriers, leading to edema formation, end organ damage, and functional deficits. The group is focused on unraveling the underlying pathomechanisms of barrier and organ dysfunction in order to advance diagnostic and preventive strategies. In this context, current studies address trauma-induced acute kidney injury (TRAKI), the significance of hemorrhagic shock as a driver of posttraumatic barrier and organ damage, systemic inflammation, and the role of adipose tissue after trauma.

Rebecca is a member of the Collaborative Research Center 1149 and has received funding from the Hertha-Nathorff- and the Baustein program of Ulm University as well as from the CRC 1149

Dr. Alberto Catanese is a postdoctoral researcher at the Institute of Anatomy and Cell Biology led by Prof. Dr. Tobias Boeckers, where he is responsible for the coordination of the projects focusing on neurodegenerative diseases.

The main focus of this working group (Cell biology of neurodegenerative diseases) is understanding the pathomechanisms leading to the selective loss of motor neurons in amyotrophic lateral sclerosis (ALS). Specific attention is given to the alterations affecting the degradative mechanisms (e.g., autophagy) and how these defects lead to synaptic failure during ALS progression. In order to answer these questions, human induced pluripotent stem cells (hiPSC) represent a patient-related valuable tool that can be used to generate 2- and 3-D in vitro models that are combined to a variety of cutting-edge technologies such as multi-omics, optogenetics, as well as novel therapeutic strategies like antisense oligonucleotides.

The ongoing projects are currently supported by the anatomical Institute, the German Center for Neurodegenerative Diseases (DZNE, Ulm site), the Bausteinprogramm of Ulm University, by the Else Kröner-Fresenius-Stiftung and the DFG.

Dr. Sofia Meyer zu Reckendorf

Dr. Sofia Meyer zu Reckendorf is a postdoctoral research fellow in the working group of Prof. Dr. Bernd Knöll in the institute of Physiological Chemistry (head: Prof. Dr. Thomas Wirth). Her research field focuses on regeneration of injured peripheral nerves.

Peripheral nerve injury usually affects young adult patients. Although animal experiments show that peripheral nerves have the intrinsic capacity to regenerate, functional regeneration in humans is often very limited. This results permanent impaired motoric and sensory functions of the affected extremities as well as chronic pain. In recent years, Sofia has established an ex vivo system to investigate regeneration associated processes in human and murine nerves. Thereby, she identified that regulation of the lipid metabolism (regulated mainly by the transcription factor PPARg) and of bioactive lipids (e.g. S1P) are major drivers of nerve regeneration in rodents, which are missing in human patients. Both, lipid metabolism and the presence of bioactive lipids can be pharmacologically modulated, making them a perfect target for a potential pharmacological treatment in patients.

In her current research, Sofia is combining in and ex vivo studies with the investigation of human nerve tissue in a translational approach in order to further characterize the role of lipid metabolism and bioactive lipids in the process of peripheral nerve regeneration.

 Sofia is funded by the DFG and is member of the Collaborative Research Center 1149 with title “Danger Response, Disturbance Factors and Regenerative Potential after Acute Trauma”.

Dr. Sabine Vettorazzi is a junior group leader at the Institute of Comparative Molecular Endocrinology (head: Prof. Dr. Jan Tuckermann). Her major focus are mechanisms that support the resolution of inflammation.

Corticosteroid hormones are major determinants of the stress response, circadian rhythm and regulate metabolic, immunologic and tissue homeostatic processes. Corticosteroid therapy is frequently used for the treatment of inflammatory diseases such as rheumatoid arthritis or asthma. The aim is to unravel the underlying mechanism of steroid action in different cell-types and how these contribute to the beneficial effects. With the help of conditional and function-selective knockout mice for the glucocorticoid receptor (GR) cell types and novel mechanisms for anti-inflammatory activities of glucocorticoids in different inflammatory disease mouse models are investigated. In a model of lung inflammation Dr. Sabine Vettorazzi made the amazing discovery was that beneficial anti-inflammatory actions of glucocorticoids are not dependent on the inhibition of pro-inflammatory mediators. During inflammation however, glucocorticoid action requires cooperation with pro-inflammatory signaling pathways (e.g. p38) to induce anti-inflammatory genes and alternative polarization of macrophages (Vettorazzi et al. Nat Comm (2015). Macrophages are the key players during the resolution inflammation, therefore new and so far, unknown mechanism in macrophages are in focus of her research. A cyclin dependent kinase 5 (Cdk5) has a crucial role during resolving the inflammatory processes in combination with glucocorticoids (Pfänder et al. Front Immunology 2019). Not only immune cells, also non-immune cells and their cross-talk to immune cells are important targets for glucocorticoid therapy and a topic of her research in a model of rheumatoid arthritis.

Dr. Sabine Vettorazzi is a PI in the CRC1149 and the Research training group GRL2201 Pulmosens.

We are interested in survival of mature B cells after deletion of components of B cell antigen receptor (BCR) and its signaling machinery. For this purpose we are using Tamoxifen-inducible B cell specific Cre strains to delete different “floxed” alleles (immunoglobulin heavy chain, Iga, Igb, Syk) in B cells. Furthermore, we would like to translate our knowledge to murine and human B cells from established mouse models for malignant B cell development and from human patients with lymphatic disorders mainly chronic lymphocytic leukemia (CLL) respectively.

CLL is a frequent lymphoproliferative disorder of B cells. Although inhibitors targeting signal proteins involved in B cellantigen receptor (BCR) signaling constitute an important part of the current therapeutic protocols for CLL patients, the exact role of BCR signaling, ascompared to genetic aberration, in the development and progression of CLL is still controversial. We are currently investigating whether BCR expression per se is pivotal for thedevelopment and maintenance of CLL B cells,  which we used in the TCL1 mouse model.

Furthermore, we are testing, whether mutations augmenting B cell signaling influencethe course of CLL development and its severity. The Phosphatidylinositol-3-kinase(PI3K) signaling pathway is an integral part of the BCR signaling machinery and its activity is indispensable for B cell survival. It is negatively regulated by the lipidphosphatase PTEN, whose loss mimics PI3K pathway activation. Our studies focus on the pivotal role for BCR signaling in CLL development and deepen our understanding of the molecular mechanismsunderlying the genesis of CLL and for the development of new treatment strategies.

Dr. Andreas Neueder is a postdoctoral fellow in the Department of Neurology (Head: Prof. Albert Ludolph, PI: Prof. Bernhard Landwehrmeyer). His main interest is RNA based molecular mechanism leading to neurodegeneration, in particular RNA toxicity in CAG repeat disorders.

Shorter versions of huntingtin (HTT), the disease-causing gene in Huntington's disease (HD), have been detected in post-mortem brains from HD patients and mouse models of HD and a considerable amount of research highlights that these fragments play a crucial role in disease pathogenesis. Despite a huge amount of work, the exact nature of the fragments and the responsible proteases remain largely unknown. During his postdoc in the lab of Prof. Gillian Bates in London (KCL and UCL, London, UK), he could show for the first time that the smallest and most toxic fragment of HTT (exon 1 HTT) is produced by incomplete splicing of the HTT pre-mRNA and not through the action of proteases.

Dr. Neueder continues to investigate this phenomenon using a combination of molecular biology and systems biology approaches. The HD clinics in Ulm with its very large patient cohort allows for powerful analysis of clinical measures concomitantly with molecular readouts. To this end, Dr. Neueder generates and analyses 'big data' in the context of HD. These datasets come from various biological sources and are analysed using advanced network-based bioinformatics to evaluate and integrate the 'omics datasets.

Dr. Janis Müller

Dr. Janis Müller is a young investigator in the Institute of Molecular Virology (directed by Prof. Jan Münch and Prof. Frank Kirchhoff). He received his PhD in 2017 by the International Graduate School in Molecular Medicine for his work on the sexual transmission of HIV-1 and other viruses.

During his PhD, in 2015, Zika virus re-emerged to cause several outbreaks in the Americas. Infection with the virus can cause neurological complication like the Guillain-Barrée syndrome and most devastatingly teratogenic effects including fetal death and microcephaly upon infection during pregnancy. Atypically for this mosquito-transmitted virus, sexual transmissions have also been recorded and Janis Müller quickly took this virus in the focus of his research.

His work is concerned with the various transmission routes of Zika virus and how it can be prevented. Zika virus is found in plasma, saliva, urine, breast milk, semen, and vaginal fluid but how the body fluids influence its infectious potential is unclear. His research revealed that semen generally reduces flavivirus infectivity and that extracellular vesicles are responsible for this effect. The vesicles are highly abundant in semen and prevent the viral attachment to its target cells. He is now working with highly purified extracellular vesicles from various body fluids to characterize them for their composition and to understand the mechanism of viral interference.

Dr. Annabel Müller-Stierlin is a postdoctoral research fellow with a background in nutritional science and medical biometry working at the Department of Psychiatry and Psychotherapy II (head: Prof. Dr. T. Becker). She completed her PhD thesis in the field of integrated care for people experiencing severe mental illness. Over the last six years at the University of Ulm, Annabel has become familiar with health care research, health economics and implementation research.

Her primary research interest is the effectiveness, cost-effectiveness and process-outcome-evaluation of psychosocial interventions with a special focus on multi-professional teams and inter-professional collaboration. Since mental illnesses affect all areas of life, there is a need for health care services that comprise a wide range of professional disciplines. In order to provide care efficiently, it is not enough to bring together multi-professional teams, but inter-professional cooperation must be promoted through appropriate training and communication paths. Not only in mental health care, but also in research, a wide variety of disciplines must finally be united to answer important questions in psychiatry, such as antipsychotic-induced weight gain. Therefore geneticists and microbiologists should be involved in research teams besides medical doctors and health scientists.

By mediating between different professional groups, Annabel’s aim is to ensure inter-professional cooperation in care and research.

Dr. Tamara Merz

 

Dr. Tamara Merz is a postdoctoral research fellow working in the Institute of Anesthesiological Pathophysiology and Process Engineering (Head: Prof. Dr. Peter Radermacher). Her research interest is the role of the endogenously produced gaseous mediator hydrogen sulfide (H2S) in the context of stress/trauma and circulatory shock.

Circulatory shock is characterized by the failure of the circulatory system to meet the requirements of oxygen and energy substrates of the organism, leading to inadequate cellular oxygen utilization and multiple organ failure. The reduced oxygen utilization leads to a metabolic switch from mitochondrial oxidative phosphorylation to anaerobic glycolysis (Warburg effect). Hyperglycemia is an essential survival response, however it can be associated with higher mortality related to increased oxidative stress and mitochondrial damage. H2S is involved in both glucose regulation and mitochondrial respiration and it can have anti-oxidative and anti-inflammatory effects. The maintenance of H2S availability might thus attenuate shock-related metabolic dysregulation. Exogenous H2S administration is a promising therapeutic option, however due to its narrow therapeutic window, further investigation is warranted. The preservation or upregulation of the endogenous H2S enzymes could represent an alternative therapeutic strategy.

Physiological and psychological trauma/stress share a plethora of biological characteristics. Thus, another research focus (in collaboration with the Clinic of Psychosomatic Medicine and Psychotherapy) is the recently identified interaction of H2S with oxytocin (OT): OT is a known player in psychological trauma and also involved in glucose metabolism regulation. Glucocorticoids (GCs) play a role in glucose metabolism and psychological trauma as well and seem to interact with the H2S and OT system (further research in collaboration with the Institute of Comparative Molecular Endocrinology). In pre-clinical and clinical studies, the investigation of the interaction of H2S, OT and GCs during psychological and physiological stress might help to identify novel therapeutic strategies.

Dr. Ina Vernikouskaya

 

Dr. Ina Vernikouskaya is a postdoctoral research fellow working in the Clinic of Internal Medicine II (head: Prof. Dr. W. Rottbauer).

Since 2010 Ina is working in the research group for experimental cardiovascular imaging headed by Prof. Dr. V. Rasche, first as a PhD student and then since 2015 as a postdoc. In addition to purely scientific work, between May 2011 and November 2012 (before she became a mother) she accompanied the development of the Core Facility Small Animal Imaging as a deputy head. She completed her PhD thesis in the field of methodological development of magnetic resonance imaging (MRI) for new application areas for human and animal experimental questions. After pursuing her doctorate degree, Ina became familiar with a completely new field of navigation of complex interventions and over the past two years has demonstrated the advantages of augmented navigation in a direct clinical context.

Transvascular procedures are commonly performed under x-ray (XR) fluoroscopy guidance. While providing high temporal and spatial resolution, XR lacks anatomical information. Multimodal intra-procedural three-dimensional (3D) image fusion (IF) can augment the limited information available from XR with relevant anatomic soft-tissue structures. With the available fusion packages on commercial x-ray systems, a wider range of transvascular catheter interventions can potentially be supported by IF. All commercial systems, however, are proprietary, and image data, position/tracking data, algorithms, and visualization methods are not made available for independent research. Therefore in order to introduce more advanced guidance techniques into the product functionality, such as e.g. automatic cross-modal image registration, image-based tracking, automatic real-time compensation of heartbeat and respiratory motion, and to perform research, development, and validation in the field of intraprocedural image guidance, independent IF software solutions appear of high interest. Therefore the purpose of her current work is to provide a rapid prototyping framework for integration of pre-interventional anatomical and functional data with real-time XR fluoroscopy and anatomically correct documentation of the working points in 3D.

 

Dr. Julia Zinngrebe

 

Dr. med. Julia Zinngrebe is a young investigator working in the Department of Paediatrics and Adolescent Medicine.

Julia finished her studies of human medicine at Ulm University in 2014. From 2011 until 2013, she worked on her MD thesis project in the lab of Prof. Henning Walczak at University College London. Her project dealt with the question how linear ubiquitination, a certain type of post-translational modification, controls innate immune signalling mediated by Toll-like receptor (TLR) 3, and how a defect in linear ubiquitination leads to TLR3-induced autoinflammation and immunodeficiency (Zinngrebe, Rieser et al., JEM, 2016).

After completing her studies of human medicine, she joined the Department of Paediatrics and Adolescent Medicine in Ulm and continued her scientific career entering the field of paediatric leukaemia research. About every seventh patient with acute lymphoblastic leukaemia (ALL) during childhood suffers from relapse. Thus, new treatment options are urgently required. Julia evaluates the efficacy of therapeutic strategies interfering with the anti-apoptotic machinery of paediatric ALL cells. The prognosis of relapsed ALL is especially poor if the bone marrow is affected. This is why Julia also investigates how the bone marrow microenvironment influences leukaemia cell survival. As adipocytes account for up to 70 percent of the bone marrow, and given their role in the bone marrow niche of paediatric ALL is understudied and only poorly understood, Julia addresses the question how the survival and proliferation of leukemic blasts is influenced by adipocytes. Identification of possible interaction routes between adipocytes and leukemic cells shall help identifying new therapeutic targets, especially for those patients suffering from a bone marrow relapse.

 

 

Dr. Kerstin Felgentreff

Dr. Kerstin Felgentreff is a young investigator in the Clinic of Pediatric and Adolescent Medicine (head: Prof. Dr. K.-M. Debatin), Pediatric Stem Cell Transplantation, Rheumatology and Immunology. Her research focuses on DNA repair and primary immunodeficiencies.  

DNA damage occurs ubiquitously in every cell triggered by e.g. endogenous factors of metabolism, or exogenous influences such as ionizing radiation or intercalating chemical drugs. Furthermore, DNA double strand breaks are physiologically induced in the process of V(D)J recombination or isotype class switch recombination for the generation of diversified T cell and immunoglobulin receptors in lymphocyte development. Dr. Felgentreff's current interest is to investigate the role of DNA damage response in lymphocyte development by differentiating induced pluripotent stem cells (iPSC) in vitro into lymphocytic lineages.

Another project focuses on an applicable test of DNA repair biomarkers to identify patients with DNA repair defects. Genetic defects affecting DNA repair proteins can cause various immunodeficiencies due to impaired lymphocyte development and survival. The only treatment option for many of these diseases is the allogeneic hematopoietic stem cell transplantation, although associated with increased toxicity to conditioning regimens. Early diagnosis of increased radio- and chemosensitivity has a tremendous impact on treatment decisions, in particular for patients identified with immunodeficiency at birth by newborn screening.

Dr. Felix Seyfried

 

Dr. Felix Seyfried is a physician scientist in the Department of Pediatrics and Adolescent Medicine (Head: Prof. Dr. K.-M. Debatin). His major research interest is to elucidate aberrant activated survival pathways and deficient cell death signaling in B-cell precursor acute lymphoblastic leukemia (BCP-ALL), which is the most common malignancy in childhood and adolescence.

The dependency of leukemias on altered signaling pathways at diagnosis influences the disease evolution and the outcome of patients. The identification and monitoring of pathway alterations, which contribute to leukemogenesis or determine sensitivity or resistance of ALL cells to (targeted) therapy, will be useful to guide molecular therapeutic approaches. Pro- and anti-apoptotic members of the BCL-2 family proteins are key regulators of the intrinsic apoptosis pathway, therefore serving as potential targets for therapeutic intervention. Using synthetic pro-apoptotic peptides in a flow cytometry-based approach, BH3-profiling, developed by Prof. A. Letai (Dana-Farber Cancer Institute, Harvard Medical School, Boston), he identified a strong association of mitochondrial BCL-2 dependence with leukemia-free survival times after in vivo therapy of ALL patient-derived xenografts with the BCL-2-directed inhibitor venetoclax. However, some leukemias demonstrated resistance to the BCL-2 inhibitor by shifting their BCL-2-dependence to other molecules, such as BCL-XL or MCL-1. Thus, analyzing the functional interplay of mitochondrial apoptosis signaling parameters will enable to select patients who will benefit from treatment with a novel inhibitor. In current projects, dependencies of leukemias on pro-survival signals of apoptosis regulators are addressed at the functional level. The main goals of the research are to evaluate the efficacy of directed therapies in ALL, to identify mechanisms determining sensitivity or resistance and to establish strategies to predict treatment response of patients to targeted treatment prior to therapy.

 

Dr. Daniel Tews is a Postdoctoral Research Fellow at the Division of Pediatric Endocrinology and Diabetes (Head: Prof. Dr. Martin Wabitsch). His major focus is to understand the function and development of brown adipose tissue in children and adults.

Adipose tissue can be assigned to two clearly distinct subtypes, mainly based on its functional properties. White adipose tissue (WAT) is the major organ for energy storage, whereas brown adipose tissue (BAT) utilizes energy sources such as fatty acids and glucose to produce heat in a process called non-shivering thermogenesis. In contrast to earlier observations, it is now well accepted that BAT in humans is functionally active not only in neonates, but also in adults. Clinical studies have shown that BAT activity is negatively associated with body weight. In addition, activation of BAT results in an amelioration of body insulin sensitivity.

Interestingly, brown-like adipocytes can emerge in white adipose tissue depots upon chronic cold exposure or beta-adrenergic treatment, a process usually termed “browning” or “britening”. As a matter of debate, these adipocytes can either differentiate de novo from a distinct precursor pool or convert from preexisting white adipocytes.

We are currently interested in transcription factors and secreted proteins that drive brown adipogenesis in humans.

 

Dr. Tews is funded by the DFG and the Boehringer Ingelheim University Ulm Biocenter (BIU, link BIU C5). Moreover, he is deputy head of the core unit “Extracellular Flux Analyzer” (link).