The CMMC research areas The three CMMC research areas enhance and strengthen innovative molecular research with clinical reference The CMMC fosters interdisciplinary collaboration from the laboratory to the clinic as well as offers an exceptional trainin
AG Prof. Dr. Dr. Miguel A Alejandre Alcazar
· Pursuing novel molecular mechanisms and treatment strategies in bronchopulmonary dysplasia: functional role of Krüppel-like factor 4 (Klf4)
Bronchopulmonary dysplasia (BPD), a neonatal chronic lung disease, is characterised by inflammation and lung growth arrest. The lack of therapies emphasizes the need to define new therapeutical strategies. We aim to decipher the mechanistic function of Klf4 – a regulator of cell pluripotency and inflammation – in regenerative and inflammatory processes. Identification of Klf4 as a novel target to promote alveolarization could define new avenues to enable growth and regeneration of lungs with BPD.
miguel.alejandre-alcazar
uk-koeln.de
AG Dr. Bodo Beck / Dr. Janine Altmüller
· Rare renal disorders identify core aspects of renal homeostasis - an integral approach to discover fundamental molecular principles of the kidney
The project represents an innovative approach to utilize genomic profiling in Rare Kidney Disease (RKD) in order to identify new causative genes and genotypes, gain knowledge about fundamental aspects of kidney homeostasis, and improve our understanding of the genomic basis of renal disease. We aim to provide missing links that change our perception of (molecular) renal physiology in health and disease.
bodo.beckuk-koeln.de, janine.altmuelleruni-koeln.de
AG Prof. Dr. Thomas Benzing / Dr. Matthias Hackl
· The role of slit diaphragm signalling of podocytes
Over the past decade we have pioneered the concept of slit diaphragm signalling and showed that podocyte viability and function is critically controlled through proteins that were initially thought to only serve as part of a filtration barrier. This project embarks on our previous work to develop innovative strategies and novel tools to study podocyte signaling in vivo by combining functional proteomics and multiphoton imaging technologies in genetically engineered animals.
AG Prof. Dr. Matteo Bergami
· Role of astrocytes in microvasculature remodeling following brain injury
Astrocytes have emerged for playing key roles in tissue remodeling during brain repair, however the underlying mechanisms remain poorly understood. We show that acute injury and blood-brain barrier (BBB) disruption trigger the formation of a prominent mitochondrial-enriched compartment in astrocytic end-feet which regulates local metabolic signalling domains.
AG Prof. Dr. Andreas Beyer / Prof. Dr. Argyris Papantonis
· Contribution of deteriorating RNA biosynthesis to cellular ageing
Using transcriptome data from 5 animal species we have shown that the speed of RNA polymerase II(Pol-2) elongation increases with ageing. In this project we plan to further analyse this phenomenon and to better elucidate molecular mechanisms.
andreas.beyeuni-koeln.de, argyris.papantonisuni-koeln.de
AG Prof. Dr. Paul T Brinkkötter
· Mitochondrial energetics and its contribution to podocyte function
Here, we investigate the role of mitochondria in podocytes and (i) characterize how mitochondria regulate insulin signalling and (ii) identify the role of the respiratory chain for podocyte function in states of health and glomerular disease.
AG Prof. Dr. Jens C Brüning
· Fto-dependent regulation of hypothalamic neurons
Variations in the human FTO gene have been linked to obesity, altered connectivity and function of the dopaminergic neurocircuitry. We report that FTO in D2 medium spiny neurons (MSNs) of mice regulates the excitability of these cells in vitroand in vivo. Lack of FTO in D2 MSNs translates into increased locomotor activity to novelty in particular, without impairing the ability to control actions or affecting reward-driven and conditioned behaviour.
AG Dr. Sebahattin Cirak
· Primary Muscle Disease
1.Disease gene discovery for muscular dystrophies, myopathies and brain malformations.
2.Molecular disease mechanisms in congenital muscular dystrophies in particular dystroglycanopathies.
3.Protein biochemistry of enzymes involved in dystroglycan glycosylation and its translational application.
AG Dr. Martin S Denzel
· Metabolic and genetic regulation of Aging
The Denzel lab is interested in understanding the process of ageing through basic research. Ageing leads to a decline in general homeostasis and is characterized by a loss of stress resistance and a dysregulation of protein quality control.
AG Prof. Dr. Sabine Eming / Prof. Dr. Maria Leptin
· The role of TOR pathway components in skin function
A decline in skin regenerative capacity, increased skin fragility with disturbed barrier function and impaired wound healing are leading causes of increasing morbidity and mortality in the elderly. Understanding the underlying molecular and cellular mechanisms is important for the development of strategies to intervene in aging- and disease-associated loss of skin function. The aim of this project is to understand the role of the nutrition-sensing pathway, and specifically of TOR signalling, in skin homeostasis, regeneration and aging.
sabine.eminguni-koeln.de, mleptinuni-koeln.de
AG Dr. Mafalda Escobar-Henriques
· Role of mitofusin 2 in health and disease
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.
AG Prof. Dr. Dirk Isbrandt / PD Dr. Maria A Rüger / Prof. Dr. Michael Schroeter / Prof. Dr. Michael Schroeter
· Novel roles for HCN/h- and Kv7/M-currents in the development of the cerebral cortex
The aim of the Institute for Molecular and Behavioral Neuroscience is to study molecular mechanisms underlying disease-associated changes in cellular excitability using transgenic mouse models. We studied the function of HCN channels in early forebrain development by creating a mouse line with ablated h-current, and by examining the effect of HCN inhibitor on neural stem cells. Our results indicate that HCN channel function in early embryonic period is essential for normal cortical development.
dirk.isbrandt[at]uni-koeln.de, adele.rueger[at]uk-koeln.de, michael.schroeter[at]uk-koeln.de, igor.jakovcevski[at]uk-koeln.de
AG Dr. Leo Kurian
· Developmental and regenerative RNA biology
Our lab is interested in understanding the basic molecular rules by which a cell defines and maintains its identity and function. Our main focus is on understanding the molecular basis of programming and reprogramming of cell-fate decisions during embryogenesis, homeostasis and aging. Additionally, we focus on devising molecular strategies to ‘hack’ these genetic networks that programs cell-fates to induce regenerative responses upon injury.
AG Prof. Dr. Thomas Langer
· Impaired mitochondrial proteostasis in CLPB associated disease
The current project aims at elucidating the pathogenic mechanism of a mitochondrial disorder caused by mutations in the AAA+ chaperone CLPB. Patients accumulate 3-methlyglutaconic acid in the urine, a characteristic of an emerging class of mitochondrial diseases apparently associated with the loss of mitochondrial membrane integrity.
AG Prof. Dr. Carien M Niessen
· Regulation of cell and tissue architecture in skin homeostasis, regeneration and degeneration
Cytoskeletal rearrangements, altered cell polarity and cell adhesion defects are observed in a wide range of human diseases ranging from degenerative diseases to inflammatory disorders and cancer. We propose that alterations in key regulators of cell- and tissue architecture underlie a broad range of these diseases. The goal of the current proposal is to address how cadherins and aPKCs cooperate to spatiotemporally coordinate the formation and maintenance of a functional multi-layered epithelial barrier with the explicit aim to identify novel therapy targets for a range of (inflammatory) skin barrier related diseases.
AG Prof. Dr. Angelika A Noegel / Prof. Dr. Peter Nürnberg
· Role of Wnt signaling in the etiology of Filippi syndrome and ectrodactyly ectodermal dysplasia
Filippi syndrome and ectrodactyly ectodermal dysplasia without cleft lip/palate are developmental disorders characterized by craniodigital and limb deformities, respectively. These disorders have received insufficient attention in the past. We identified disease-causing DNA variants.
noegeluni-koeln.de, nuernberguni-koeln.de
AG Dr. Alvaro Rada-Iglesias
· Developmental Genomics: Transcriptional regulation in development and disease
The main interest of our laboratory is to uncover the genetic and epigenetic factors controlling the deployment of gene expression programs during vertebrate embryogenesis as well as how the disruption of these regulatory factors can lead to human congenital disease.
AG Dr. Dr. Jan Rybniker
· Comprehensive host-cell based antibiotic drug discovery
It is believed that novel screening methods and platforms are needed to generate a sufficient amount of lead molecules that will fill the gap of approved substances against a whole range of Gram-negative and Gram-positive pathogens. Structural limitations and the current lack of diversity in screening libraries asks for alternative approaches such as anti-virulence drug screens, novel phenotypic screening assays and the development of host-directed therapies.
A comprehensive antibiotic screening platform, combining several of these aspects, has the great potential of generating a substantial amount of lead compounds with diverse mechanisms of action, needed for the control of antibiotic drug resistance.
We have recently developed such a screening platform for the major human pathogen Mycobacterium tuberculosis.
AG Prof. Dr. Bernhard Schermer / PD Dr. Max C Liebau
· The role of the cilia-cell-cycle connection in tissue homeostasis of renal tubular epithelium in acute and chronic kidney diseases
Recent groundbreaking work has revealed that mutations in genes encoding proteins localized to primary cilia are causative for a large number of different human diseases, now referred to as ciliopathies. A hallmark of most ciliopathies is the development of cystic kidneys caused by aberrant proliferation of epithelial cells.
ernhard.schermeruk-koeln.de, max.liebauuk-koeln.de
AG Prof. Dr. Guenter Schwarz
· Sulfite oxidase-dependent nitric oxide synthesis: Molecular mechanism, in vivo relevance and pharmacological targeting
Ischemia/reperfusion injury underlies the progression of pathologies in various organs and is a significant cause of morbidity and mortality. Management of cardiovascular disorders critically dependents on blood pressure control by NO. With SOX, as novel NO-synthase, we found an entirely new target for pharmacological targeting of nitrite-dependent NO release. Given our previous experience in drug development, we aim to find now compounds for the treatment of hypertension disorders.
AG Prof. Dr. Gerhard Sengle / Prof. Dr. Raimund Wagener / Prof. Dr. Mats Paulsson
· Extracellular microfibrillar systems in disease pathogenesis: functional interactions in cytokine
regulation, cellular differentiation and tissue homeostasis
New strategies for treating congenital musculoskeletal disorders are needed. Current treatments are limited and aim to prolong ambulation and survival.Cellular microenvironments such as stem cell niches in muscle and bone are defined by extracellular microfibrillar networks (EMFN) which are required for tissue structure and function. EMFN made of fibrillin-1 and -2, and collagen VI with associated ligands are of particular interest since human mutations in EMFN components result in disorders with overlapping clinical features.
gsengleuni-koeln.de, raimund.wageneruni-koeln.de, mats.paulssonuni-koeln.de
AG Prof. Dr. Dr. Dres. h.c. Wilhelm Stoffel
· Antagonistic pleiotropy of the Δ6-fatty acid desaturase (fads2) gene in disease and senescence. ω3- and ω6-Polyunsaturated fatty acids in Δ6-fatty acid desaturase (fads2-/-) deficiency
We generated an unbiased mammalian model, the fads2-/- mouse, deprived of ω3- and ω6-PUFA synthesis. The fads2-/- mouse is auxotrophic and an ideal experimental platform for deciphering the molecular basis underlying the role of PUFAs in cell biology, membrane and nutritional research and altered lipid homeostasis in related pathologies. Fads2 is an antagonistic pleiotropic gene.
AG Prof. Dr. Aleksandra Trifunovic
· Manipulation of CLPP protease to complement mitochondrial respiratory deficiency
Our project explored possible therapeutic intervention in a largest group of mitochondrial diseases that directly affect the function of mitochondrial tRNAs. We presented the first evidence that manipulation of the levels of mitochondrial matrix protease, CLPP could ameliorate mitochondrial encephalopathy, caused by loss of mitochondrial aspartate tRNA synthase (DARS2), holding a promise for further exploration of specific protease inhibitors in treatment of mitochondrial diseases.
aleksandra.trifunovicuk-koeln.de
AG Prof. Dr. Rudolf Wiesner
· Maintenance of mtDNA integrity in muscle stem cells
Tissue stem cells (SC) show a multitude of mechanisms to avoid or repair damage, including low mitochondrial mass and minimal use of oxidative metabolism. However, mitochondrial mass must be dramatically expanded during SC differentiation, thus, intactness of mtDNA is essential. The aim of this project is to test (i) if mtDNA is only rarely replicated in quiescent muscle SCs or, alternatively, (ii) that it is purified during recruitment, i.e. wt mtDNA copies are kept in MuSCs while ΔmtDNA is passed to the progeny.
AG Prof. Dr. Brunhilde Wirth
· Unraveling the molecular and cellular mechanism underlying spinal muscular atrophy by use of genetic modifiers
Spinal muscular atrophy (SMA) is caused by homozygous absence of the survival motor neuron gene 1(SMN1) and inability of SMN2to compensate for the SMN1loss. We found that increased levels of plastin 3 (PLS3) and reduced levels of neurocalcin delta (NCALD) protect against SMA in humans and across species (zebrafish, worm and mice). However, the molecular genetic cause for the modified expression of these modifiers in asymptomatic SMN1-deleted individuals is not understood, but relevant for future therapies.