Career Advancement Groups

Understanding the molecular basis of stress, longevity, and aging

My research group entitled “Computational Biology of Aging” focuses primarily on the application of computational approaches to explore the interplay between multiple layers of biological organisation and their phenotypic characterisation. Specifically, this entails the analysis of several cohorts at the University Hospital Cologne (UHC) where data integration, predictive/statistical modelling and network biology approaches are the key methodologies that are applied to improve our understanding of the associated clinical questions. In parallel, my group continues to explore the impact of exogenous stress on organism function. In recent years this was centred on non-human species to improve our understanding of the impact of exogenous stressors and explore the thresholds at which adverse events occur  with plans to explore human centered data via new grant opportunities.

• CMMC assoc. JRG 06 and CAP 20 - Antczak
• Antczak Lab
• Publications - Philipp Antczak - Link to PubMed

Dissecting the molecular mechanisms of tumor evolution and therapy resistance

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.  

• CMMC CAP 18 - Brägelmann
• Publications - Johannes Brägelmann - Link to PubMed

Immunobiology of glomerular diseases

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:

1. Characterization of the anti-inflammatory properties of cDC1 and checkpoint proteins: Based on our recent data, cDC1 have robust anti-inflammatory properties in glomerulonephritis. Therefore, we use kidney disease models, flow cytometry and advanced imaging methods to understand their exact molecular function.
2. Analysis of glomerular pro-inflammatory signaling: Glomerulonephritis is a specific inflammation of the renal filtering unit. Renal cells like podocytes are among the first responders to tissue injury. We analyze and try to modulate the inflammatory environment in glomeruli to prevent disease progression right where it starts.
3. Immune cell metabolism in renal diseases. Metabolism is a fundamental prerequisite for each cell’s activation and function. Our aim is to investigate the involvement of key metabolic pathways in renal disease like the TCA cycle.

• CMMC CAP 17 - Brähler
• Publications - Sebastian Brähler - Link to PubMed

Investigating the metabolic determinants of T cell immunological memory

In recent years, the emerging field of immunometabolism has started to unveil the role of metabolism in shaping immune function, and to reveal how modulating cell or organismal metabolism can affect immune cell differentiation.
“With my team I am investigating how mitochondrial function is regulated in T cells in health and disease and how its dysregulation during ageing or pathology results in impaired or altered immune response. My long-term goal is to clarify the transcriptional and micro-environmental mechanisms involved in the development of long-term immune memory and define how metabolic plasticity modulates cellular responses to stress and immune chal-lenges” Mauro Corrado comments, whose research group is located in the CECAD Research Building.

• CMMC CAP 21 - Corrado
• CMMC IPF-Project B 03 - Epigenetic-metabolic crosstalk in the development of T cell immunological memory
• Publications - Mauro Corrado - Link to PubMed

Role of mitofusin 2 in health and disease

Mitochondria are mobile organelles that constantly fuse and divide. These properties play a central role in quality control processes and energy expenditure. Mitochondrial fusion depends on the mitofusin proteins MFN1 and MFN2. Dysfunction of MFN2 causes the neuropathy Charcot-Marie-Tooth type 2A, is associated with Parkinson’s disease and with cardiovascular pathologies, but is also linked with type 2 diabetes and obesity and with non-alcoholic fatty liver disease and cancer. We aim at understanding at the molecular level the disease-underlying functions of MFN2.

• CMMC CAP 14 - Escobar-Henriques
• Publications - Mafalda Escobar-Henriques - Link to PubMed

Myeloid Leukocytes in Cardiovascular and Systemic Inflammation

Dr. Hoyer’s research group focuses on myeloid leukocyte biology in cardiovascular disease. Inflammation’s involvement in various cardiovascular pathologies has garnered much attention in recent years, and the role and function of myeloid leukocytes are increasingly recognized. Certain features of myeloid cells promote tissue maintenance and repair. Excessive inflammatory activity, on the contrary, exacerbates injury and impacts systemic complications. Mechanisms shifting myeloid cells’ responses towards healing while minimizing collateral tissue damage remain insufficiently understood. Aiming to find novel therapeutic ways to mitigate cardiovascular inflammation and halt disease progression, Felix Hoyer’s group focuses on how

1. systemic mechanisms regulate the supply of inflammatory myeloid cells, and
2. differentiated myeloid effector cells influence cardiovascular disease progression and systemic inflammation.

• CMMC CAP 22 - Hoyer
• Publications - Friedrich F Hoyer - Link to PubMed

Microglia Cell Death and Senescence in Tauopathies

The Ising lab focuses on the role of cell death and senescence of microglia, the innate immune cells of the brain, in the development and progression of aging-associated tauopathies such as Alzheimer’s disease.

• CMMC CAP 29 - Ising
• Publications - Christina Ising - Link to PubMed

Maintenance of Genome Stability and Nuclear Integrity

We focus on two cellular processes that are often deregulated during aging and in aging-associated diseases, such as cancer:

• Genome stability maintenance
• Trafficking through the nuclear pore complex (NPC)
   
• CMMC CAP 30 - Leidecker
• Publications - Leidecker - Link to PubMed

Functional Bio-inspired Porous Materials

PD Dr. Maleki's group focuses on the rational design of self-assembled and sol-gel derived bio-inspired hybrid smart nanomaterials as a theragenerative systems (combination of therapy and regeneration) with improved biomimetic microstructure, mechanical, self-healing and shape morphing properties for minimally invasive bone cancer therapy and bone regeneration and drug delivery purposes.

• CMMC CAP 35 and assoc. CMMC JRG 08 - Maleki
• Maleki Lab - Functional Porous Materials
• Publications - Hajar Maleki - Link to PubMed

Deciphering the functional relevance and signal transduction network of protein kinases in the tumor microenvironment

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”.

• CMMC CAP 19 - Nguyen
• Publications - Phuong-Hien Nguyen - Link to PubMed

Investigating the Effects of Post-Translational Mechanisms on ECM Homeostasis in Human Disease and Aging and Exploring Potential Modulations as Therapeutic Target

• CMMC CAP 31 - Nüchel
• Publications - Julian Nüchel - Link to PubMed

Uncovering the mechanisms regulating mitochondrial dynamics during cell division

• CMMC CAP 32 - Piano
• CMMC IPF-Project C 18
• Publications - Valentina Piano - Link to PubMed

Translational Immunology in Infectious Diseases

The emergence of multidrug-resistant (MDR) bacteria is a major public health concern with increasing mortality throughout the world. While nowadays new drugs and therapeutic approaches are on the rise for many diseases, the clinical implementation of innovative therapeutics in the treatment of bacterial infections is stagnating. To overcome the limited amount of new antibiotics, the development of immunotherapies, which enhance the host immune response, seems reasonable. This approach might be particularly effective in immunocompromised patients such as critically ill patients or patients receiving chemotherapy. Accordingly, our group explores the host-pathogen interactions of clinically relevant bacteria to develop new powerful immunotherapeutic strategies in the fight against MDR bacteria.

• CMMC assoc. JRG 09 and CAP 27
• Publications - Alexander Simonis - Link to PubMed

Protein Quality Control and Stress Response

We are interested in understanding the mechanisms governing the homeostasis of the cellular proteome (proteostasis). Protein structures are highly complex and dynamic, and several stresses can compromise their integrity. Therefore, cells are equipped with an intricate and adaptive network of factors ensuring protein synthesis, folding, trafficking, conformational maintenance, and degradation. Importantly, misfolded proteins are not only dysfunctional, but they can also coalesce into potentially toxic aggregates. Importantly, misfolded proteins are not only dysfunctional, but they can also coalesce into potentially toxic aggregates. These represent a hallmark of many aging-associated neurodegenerative disorders, such as Parkinson’s and Alzheimer’s diseases. Our aims are to understand how protein quality control pathways distinguish defective from functional proteins, how the decision between repair and elimination is made, and how these processes are activated under stress and pathological conditions.

• CMMC CAP 33 and assoc. CMMC JRG 05 - Trentini
• Trentini Lab
• Publications - Débora Trentini - Link to PubMed

Investigation of the Mechanisms and Triggers leading to a Detrimental Retinal Immune Response during AAV-based Retinal Gene Therapy

• CMMC CAP 34 - Wolf
• CMMC IPF-B 07
• Publications - Anne Wolf - Link to PubMed

Molecular Mechanisms and Gene Therapy approaches for Genetic and Sporadic Neurodegenerative Diseases

Frontotemporal Dementia (FTD) and variants thereof, such as Progressive Supranuclear Palsy (PSP), Picks disease (PiD) and Corticobasal Degeneration (CBD) can be classified as ageing-associated taupathies. These taupathies, as well as Alzheimer’s disease  (AD), the most prevalent form of dementia, and other TAU and mitochondria related dementia-causing syndromes are devastating disorders that impose a huge burden on society. Genetic variants, splicing defects and pathological axodendritic distribution of the protein TAU cause or significantly contribute to these diseases. Understanding the neurobiological, cellular and molecular mechanisms underlying TAU physiology in disease relevant human cells is crucial for developing successful therapeutic approaches for AD and associated diseases.
Our recently established junior research group: “Functional Genetics of Neurodegeneration and Neurological Disease” currently works on the elucidation of pathomechanisms of genetic and sporadic forms of tauopathies, including AD and mitochondriopathies. By better understanding the molecular disease mechanisms, we strive to identify and test novel therapeutic approaches for these currently incurable diseases. As model systems, we focus on human iPSC-derived neurons (iNs), TAU-humanized mice and primary neurons derrived from these, as well as several other cell types (e.g. patient-derived primary fibroblasts). We use lentiviruses (LV), state of the art microscopy (i.a. calcium imaging, photoconversion/optogenetics, STED-nanoscopy) and omics approaches ((sc)RNAseq and proteomics) to elucidate disease mechanisms and test therapeutic approaches in disease-relevant human neurons and in TAU-humanized mice.

• CMMC CAP 28 - Zempel
• Publications - Hans Zempel - Link to PubMed