The Career Advancement Program (CAP) has been specifically designed to support high-potential mid-career scientists of the Medical Faculty aiming for full professorships or equivalent leadership positions at non-university research institutions. If required the CMMC provides temporarily access to high-quality laboratory space in the CMMC Research Building, access to the research infrastructure and administrative support as well as support aimed at enhancing their scientific expertise and professional skills base. The CMMC currently supports the following 8 CAP-groups.
A major factor limiting the survival of cancer patients is the lack of durable treatment response and the emergence of therapy resistant disease. The causal genetic and epigenetic mechanisms driving tumor evolution and therapy resistance are still largely unknown. However, we consider a detailed knowledge of these processes vital in order to improve existing and design novel treatment strategies. Accordingly, our group explores the molecular determinants of tumor development and therapy response by combining forward genetic screens and data-driven molecular biology with a special focus on lung and head and neck cancer.
The kidney contains a dense network of immune cells, which is of central importance for organ homeostasis but can also lead to tissue damage and ultimately renal failure. While both kidney biology and renal immunology have made tremendous progress in the past, the interaction between kidney cells like tubulus cells or podocytes and immune cells is still poorly understood.
We are currently investigating the following areas:
The overall aim of our group is investigating the reactivation of lymphocytes in non-lymphoid tissue: following lymphocyte priming, effector T cell recruit to peripheral tissues to fulfil both helper and executive functions. Our goal is to better understand the molecular mechanisms driving this process, to identify and characterize cellular interactions involved and to further understand microenvironmental cues modulating the functional restimulation of lymphocytes in peripheral tissue.
Despite decades of research, lung cancer remains the most common cause of cancer-related death. Most recently multiple promising approaches, reigniting a patient´s own adaptive anti-tumor immunity, fueled hope to identify novel treatment regimens for this aggressive tumor. Here, we will employ highly predictive in vivo models for most efficient bench-to-bedside translation of multimodal anticancer therapy consisting of CDK4/6 inhibition, radiation therapy, and immune checkpoint inhibition.
Loss of corneal transparency due to severe inflammation and neovascularization is one of the leading causes of blindness worldwide. This project aims to investigate the functional relationship between myeloid cells and corneal neovascularization in various clinically relevant neovascular disease models in mice. The findings of this work will contribute to future immunomodulatory therapeutic interventions promoting corneal repair and preventing corneal disease.
The definition of cancer hallmarks has significantly expanded in the last decades and cancer is no longer considered a disease of only malignant cells, but a highly complex tissue comprising tumor cells and their tumor microenvironment (TME).
“My research is based on the finding that non-receptor tyrosine kinases are functionally essential for the creation of a proneoplastic, microenvironmental niche. The distinct, cell-type specific patterns of substrate activation induced by kinases may lead to a differential activation of transcription factors and, as a consequence, to a cell type-specific modulation of cellular functions”, Nguyen comments and adds ”Because many kinase inhibitors are readily available, understanding these kinases’ functions in the TME will be useful to design improved anti-cancer therapies, particularly to target the immune- and metastatic niches”.
Vision is a key sensory function. Clear vision depends on transparency of the structures of the visual axis. Consequently, normal corneal tissue (the “windscreen of the eye”) is in an avascular and low inflammatory state. The limbal epithelial stem cells (LESC) maintain the integrity of the corneal epithelium thus preventing neovascularization, stromal scarring and conjunctivalisation. Although it has been proven both clinically and experimentally that LESCs destruction compromises corneal avascularity, the exact mechanisms by which this is achieved remain unidentified.
Our group focuses on elucidating these mechanisms and aims to identify new LESC-related regulators of corneal neovascularisation which will lead to new therapeutic options (we are part of FOR2240, “(Lymph)angiogenesis and cellular immunity in inflammatory diseases of the eye”).
Immune checkpoint inhibition (CKI) demonstrated remarkable efficacy in several kinds of cancer, representing a major breakthrough in cancer therapy. These therapies are unique, as the primary target is not the tumor cell itself, but the crosstalk between immune cells and cancer cells in the tumor microenvironment. We described a negative prognostic impact of PD-L1 expression on tumor cells in esophago-gastric adenocarcinoma (GC) and CKI is effective in metastatic disease. Interestingly, efficacy of CKI is often not limited to patients with expression of the relevant protein on tumor cells. Recent publications demonstrate that expression of PD-L1 on tumor-infiltrating lymphocytes and tumor cells are of similar importance for immune escape, which explains treatment response in patients with PD-L1 negative tumors. Despite the promising results of early studies, only a minor fraction of patients responds to CKI. Preexisting endogenous immune responses seem to be crucial for immune checkpoint inhibition. A successful immune recognition depends on a broad spectrum of immune-related tumor cell intrinsic or extrinsic aspects and can so far only be predicted partially by very few markers (e.g. mutational burden, PD-L1 expression). Hence, multidimensional analyses of tumor immunogenicity including the immune infiltrate, private and shared tumor antigens, tumor specific immune response and immune escape are crucial to further improve therapeutic efficacy and translational research for this novel aspect of cancer therapy.
We aim to decipher endogenous tumor-specific immune response with a clear focus on GI Cancer. Detailed analyses of endogenous immune response against private and shared antigens will be performed using genomic and functional analyses in preclinical models, untreated tumor samples and patients receiving immune checkpoint inhibition.
CAP 14 - Mafalda Escobar-Henriques "Role of mitofusin 2 in health and disease"
CAP 10 - Miguel A Alcazar "Pursuing novel molecular mechanisms and treatment strategies in bronchopulmonary dysplasia: functional role of Krüppel-like factor 4 (Klf4)"
CAP 09 - Roland Ullrich "Targeting tumor angiogenesis"
CAP 08 - Jan Rybniker "Comprehensive host-cell based antibiotic drug discovery"
CAP 07 - Stephan Rosenkranz "Role of PI3Kd in atherosclerosis"
CAP 06 - Martin Peifer "Computational cancer genomics"
CAP 04 - Catherin Niemann "Molecular function of Lef1 mutations (E45K/S61P and DNLef1) in epithelial tissues and cancer"
CAP 03 - Helmar Lehman "Mechanisms of axonal injury in neuroinflammation and neurotoxicity"
CAP 02 - Mathieu Clement-Ziza "Mechanisms of tumor development: intrinsic and extrinsic control of cell proliferation and tissue invasion"
CAP 01 - Paul T Brinkötter "Mitochondrial dysfunction and glomerular disease"