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Personalised Immunotherapy
Our motivation is to address fundamental questions of human immunology and translate them into personalized therapies and diagnostics. Specifically, our laboratory discovers new applications of antibodies and B cells to treat and prevent human infectious diseases. Effective vaccines against some viruses that escape antibody responses remain elusive. To tackle this challenge, we develop methods to better understand B cell responses, the cells that produce antibodies. We design tailored vaccines and provide novel solutions for infection diagnostics.
Computational Biology for Individualised Medicine
Infections are among the biggest threats to health and the most significant causes of death worldwide. Our aim is to reveal the host genetic risk factors and their downstream molecular pathways, which are crucial to make progress in understanding and treating infectious diseases in an individualised manner as well as to improve the identification of patients at risk. The department of the HZI is part of the developing CiiM and currently housed at the TWINCORE in Hannover. Students and postdocs – We are always looking for bright and enthusiastic students and postdocs (funded by e.g. the ERC starting grant). For more about our projects, please contact us by email.
Individualised Medicine for Viral Infections
Opportunistic infections remain a serious threat to immunocompromised individuals, such as transplant recipients. We study opportunistic herpes viruses, such as the cytomegalovirus (CMV) by developing unique technologies for real-time measurement of virus growth, allowing us rapid identification of antiviral activity of primary samples and virtually any immune cell subset. This allows us to identify at-risk populations and develop targeted antiviral therapies for treatment and prevention of opportunistic viral infections. In the course of the COVID pandemic, our expertise in virus genetics was used to clone pseudoviruses expressing variants of the SARS-CoV-2 spike protein for the assessment of the neutralization capacity of sera or monoclonal antibodies, and this technology is pursued in the identification of correlates of immune protection in vaccinated or convalescent populations. We team with local and international teams of physicians and epidemiologists, providing technical support and scientific advice on complex laboratory serological diagnostics. In March 2019, Prof Dr. Dr. Luka Cicin-Sain was jointly appointed by the MHH (Hannover Medical School) and HZI (Helmholtz Centre for Infection Research) as CIIM Professor for "Individualised Medicine of Viral Infections", and as of 2021 he leads the CiiM-associated Department of “Viral Immunology” (VIRI) at the Helmholtz Centre for Infection Research in Braunschweig.
Computational Biology for Infection Research
The group studies microbial communities, including bacteria, viruses and eukaryotic community members, in the context of human health and disease. Direct metagenome, -transcriptome or -proteome sequencing of microbial community samples enables the study of microorganisms that cannot be obtained in pure culture, corresponding to most of the microbial world.
Clinical Bioinformatics
Personalized medicine offers a significant opportunity to enhance public health by accounting for individual variability in genes, environment, and lifestyle. The "Clinical Bioinformatics" research group follows this direction, aiming to unravel the intricate molecular mechanisms underlying infection and aging. Through this pursuit, we strive to develop precise, individualized treatment strategies. Our research aims to develop and apply "bioinformatics approaches" to pinpoint the genetic and epigenetic factors influencing infection-induced immune responses by integrating multi-omics data from patients and constructing computational models that predict an individual’s risk of infectious diseases. We interact with experimental collaborators and clinical experts to verify our findings and promote their translation into medical treatments or diagnostic procedures. Our ultimate goal is to contribute to the main research focus of CiiM/MHH: the tailored and improved prevention, diagnosis, and treatment of infectious diseases and cancer for individual patients or patient groups. Within this framework, the team led by Prof. Dr. Cheng-Jian Xu is primarily dedicated to the domains of diagnosis, risk assessment, early detection, and patient stratification.
Immunology of Viral Hepatitis and Infections in Liver Cirrhosis
Hepatitis viruses A-E pose a major health challenge worldwide. Acute infections with hepatitis B (HBV), C (HCV), D (HDV) or E (HEV) can progress to chronic hepatitis and lead to liver cirrhosis and hepatocellular carcinoma. Chronic viral hepatitis affects more than 350 million people worldwide. While direct-acting antiviral drugs provide a cure for chronic hepatitis C, the long-term effects on the immune system after the infection is cured are not fully understood. While direct-acting antiviral nucleos(t)ide analogues can treat chronic hepatitis B, complete cure is rare. Innovative approaches, particularly modulation of the immune response to HBV, hold promise for a cure. Chronic hepatitis D is always a co-infection with HBV and thus concepts to cure HBV will also target HDV. In chronic hepatitis E, which is unique in immunocompromised patients such as organ transplant patients, enhancing the immune response against HEV may be a novel strategy. In people with cirrhosis of the liver, regardless of the cause, the immune system is compromised and susceptibility to infection is increased. In particular, bacterial infections of the peritoneal cavity due to ascites contribute significantly to disease progression. Our research group focuses on understanding immune responses to hepatitis viruses and developing biomarkers to better stratify patients for new therapeutic strategies to modulate the host immune system in the effort to combat chronic viral hepatitis. In addition, we are exploring the mechanisms underlying immunodeficiency in liver cirrhosis and investigating immunomodulation strategies to improve survival in these vulnerable patients.
Infection Biology
Microbial communities consisting of bacteria, fungi, and viruses colonize all surfaces of the human body. These communities are collectively referred to as the microbiome. The composition of the microbiome varies between individuals and also within a single individual over the course of a lifetime. Key influencing factors at the beginning of life include mode of birth and diet. Later in life, the use of antibiotics and other medications, long-term dietary habits, health status, and sport and stress also play a role. In recent years, numerous studies have investigated the extent to which the microbiome and its changes contribute to our health and disease development. In animal models and clinical studies, it has been demonstrated that certain changes in the microbiome influence the development or course of, for example, chronic inflammatory bowel diseases, or susceptibility to infection. This has led to the development of novel microbiome-based therapies, which are currently being investigated in animal models and clinical studies. Till Strowig’s department takes an interdisciplinary approach, combining microbiology, immunology, and bioinformatics to develop a molecular understanding of the complex interactions between the gut microbiome and the host. This research provides a vital foundation for developing personalized prevention and treatment strategies. Close collaboration between the MHH and the HZI at the CiiM will enable research findings from basic research to be translated more directly into practice in the future. One example of this is the successful establishment of a microbiome analysis platform. This platform is crucial for studying how the microbiome influences a host's susceptibility to infections, and it has already been utilized for various patient groups (RESIST-SeniorIndividuals, LöwenKIDS, and RheumaVOR). Another example is identifying specific microbiome components that can be used in preclinical models to prevent colonization by disease-promoting bacteria.
CAIMed Group 1b: AI and Bioinformatics
To advance our understanding of diseases and their personalized treatment, the identification of genetic risk factors and their molecular signaling pathways, as well as the development of predictive models for disease progression and severity, are of the utmost importance. At MHH, existing and planned patient cohorts with state-of-the-art (single-cell) multi-omics data are available. Our junior research group focuses on the pre-processing (integration) of molecular data to generate standardized, high-quality datasets for the analyses conducted by other CAIMed junior research groups. The aim is to evaluate these data at scale using innovative AI-based methods. This includes identification of factors that correlate with disease severity and progression in order to predict individual responses to diseases and treatments, thereby establishing a molecular basis for the stratification of patient groups. Currently, the group is engaged in the evaluation of datasets for the prediction of long-COVID, within the framework of the BMFTR-funded projects AID-PAIS and FEDCOV, which work on data from several German COVID-19 cohorts and the UK-Biobank. In addition, datasets from other chronic viral infections and associated fatigue syndromes (e.g., ME/CFS), such as those arising from chronic hepatitis C virus infections, are being integrated. The overarching goal is to facilitate the translation of these mathematical models into clinical treatment, diagnostic, and predictive applications as a critical first step toward individualized prevention and therapy.