Seminar Series
Do · 28.05.2026
Epigenetic Regulation of Cellular Homeostasis Amid Transcription-Blocking DNA Damage During Development and Aging, project 3
Speaker: Angelina Job Kolady (Yao Wang)
Seminar Series
Do · 11.06.2026
Investigate the effects of Metaxin 2 loss on nuclear morphology and cellular senescensce
Speaker: Bora Görgül (Valentina Piano)
Seminar Series
Do · 25.06.2026
Endomembranes in Cell Division: Connecting Organelle Dynamics and Genomic Stability
Guest: Dr. Nuria Ferrándiz
Seminar Series
Do · 09.07.2026
"Coordination of DNA Damage Response and Aging by Ubiquitin Signaling", project 4
Speaker: Maria Pandrea
Seminar Series
Mo – Mi | 07. – 09.09.2026
DNA Repair Meeting 2026
co-hosted by: DGDR and FOR5504
Seminar Series
Mi · 09.09.2026
Fritz Thyssen Forum
Prof. Dr. Jan Karlseder (San Diego)
Seminar Series
Do · 10.09.2026
"Genome Instability Syndromes as a Toolbox to Unravel Novel DNA Repair Pathways", (project 5)
Speaker: Maxim Hützen
Seminar Series
Do · 24.09.2026
tba
Guest: Prof. Jan Vijg
Seminar Series
Do · 08.10.2026
"Mechanism and Consequences of SLX4IP- and ERCC1-XPF-dependent Telomere Dysfunction", project 6
Speaker: Francesca Pandolfo (Stephanie Panier)
Seminar Series
Do · 28.05.2026
Epigenetic Regulation of Cellular Homeostasis Amid Transcription-Blocking DNA Damage During Development and Aging, project 3
The research project focuses on how epigenetic mechanisms, particularly the deposition of H3K4me2 by the MLL/COMPASS complex, are regulated in response to transcription-blocking DNA damage. It investigates how this histone modification aids in the recovery of transcription elongation and the maintenance of cellular homeostasis during both development and aging. Using *C. elegans*, the study seeks to understand the physiological consequences of genome instability, particularly how impaired or enhanced deposition of H3K4me2 influences growth and longevity .
Seminar Series
Do · 11.06.2026
Investigate the effects of Metaxin 2 loss on nuclear morphology and cellular senescensce
host lab: Valentina Piano (CMMC)
We investigate the direct effects of MTX2 depletion in human cell lines. In particular, we examine whether loss of MTX2 or disease-associated mutations affect mitochondrial transport and interfere with proper mitochondrial segregation during cell division. We further study how these defects may contribute to nuclear abnormalities, including chromosome segregation errors and the formation of chromatin bridges during cytokinesis. In addition, we address whether impaired mitotic progression promotes senescence and thereby contributes to accelerated cellular ageing and the progeroid phenotype.
Seminar Series
Do · 25.06.2026
Seminar talk by Dr. Nuria Ferrándiz from CIC - Centro de Investigación del Cáncer,
Campus Miguel de Unamuno, Salamanca, Spain
Most solid tumours are aneuploid, with higher rates of chromosome instability (CIN), making the understanding of the mechanisms of chromosome missegregation a crucial goal in cancer cell biology. Furthermore, mitotic errors can also lead to the formation of micronuclei (MN), which are susceptible to nuclear envelope rupture and can result in extensive genomic rearrangements, such as those commonly observed in chromothripsis. While the spindle mechanics that ensure proper genome segregation during cell division have been extensively studied, less attention has been given to other structures within mitotic cells, such as intracellular membranes and organelles, collectively known as endomembranes, including the nuclear envelope (NE) and Golgi remnants, endoplasmic reticulum (ER), and vesicles. Recent studies from our lab and others have shown that endomembranes, particularly the ER, can impair chromosome dynamics and promote aneuploidy and MN formation.
In our laboratory, our primary aim is to develop a comprehensive understanding of NE organization, remodelling, and reassembly during cell division, with a specific emphasis on the recruitment of NE proteins to chromatin during mitotic exit. To address these research aims, we have outlined specific goals, including:
To achieve these objectives, we employ a multidisciplinary approach encompassing molecular biology, genome editing, biochemistry, and advanced imaging techniques to decipher organelle dynamics in mammalian cells.
Seminar Series
Do · 09.07.2026
Coordination of DNA Damage Response and Aging by Ubiquitin Signaling
lab: Thorsten Hoppe
We investigate how ubiquitin signaling coordinates the DNA damage response and contributes to genome stability during development and aging. A particular focus lies on the role of the ubiquitin ligase UFD-2 and associated factors in the repair of DNA double-strand breaks. By analyzing the spatiotemporal regulation of ubiquitin-dependent repair mechanisms, we aim to understand how defects in these pathways promote genome instability and age-related decline. To address this, the project combines biochemical, proteomic, genetic, and imaging approaches in order to link DNA repair regulation with physiological consequences for longevity and tissue function.
Seminar Series
Mo – Mi | 07. – 09.09.2026
on Physiological Causes and Consequences of Genome Instability
September 07 - 09 | Cologne, Germany
Registration Deadline: May 31st 2026
Seminar Series
Mi · 09.09.2026
Fritz Thyssen Forum
co-hosted by CECAD Research Center
speaker: Prof. Dr. Jan Karlseder (San Diego)
September 09 2026
Fritz Thyssen Forum
Cologne, Germany
Seminar Series
Do · 10.09.2026
We aim to explore the causes and consequences of deregulated DNA repair to explain important phenotypes observed in our novel human genome instability syndromes. Importantly, these insights will serve as a blueprint to understand the intricate relationship between the DDR, protein homeostasis and neurodegeneration.
Seminar Series
Do · 24.09.2026
Seminar talk by Prof. Jan Vijg from Albert Einstein College of Medicine, New York.
Genome Instability in Aging and Disease
Genome instability, i.e., the tendency of the genome to acquire mutations and epimutations, underlies human genetic disease, causally contributes to cancer and has also been implicated in aging and age-related, degenerative conditions other than cancer. Little is known about the mechanisms that give rise to spontaneous changes in the genome or epigenome and how this may lead, in somatic cells, to increased cancer risk and loss of organ and tissue function with age. We study genome and epigenome instability as a function of age in various model organisms, including mouse and fruit fly, and its consequences in terms of alterations in tissue-specific patterns of gene regulation.
In the past we developed transgenic reporter systems in mouse and fruit fly, which allowed us to determine tissue-specific frequencies of various forms of genome instability, e.g., point mutations, deletions, translocations. By crossing the mutational reporter animals with mutants harboring specific defects in various genome maintenance pathways, the relevance of these pathways for the accumulation of specific forms of genome instability is assessed, in relation to the pathophysiology of aging. Similarly, by using knockdown approaches we assess the effect of specific genes implicated in longevity and healthy aging, e.g., SOD, FOXO, SIR2, on genome integrity.
We are currently focused on single-cell genomics to assess mutation frequencies and spectra in human tissues during aging. To gain insight into the possible functional consequences of random somatic mutations we use single-cell multiomics assays to link specific mutations to transcriptional and translational end point.
Seminar Series
Do · 08.10.2026
lab: Stephanie Panier
Somatic cells have finite replicative lifespans because telomeres undergo progressive shortening after DNA replication, which can lead to genome instability and induce senescence. Telomere dysfunction has profound physiological consequences and promotes the accelerated development of many age-associated pathologies such as tumorigenesis and kidney disease. We have previously described the adapter protein SLX4IP as an important regulator of recombination-based Alternative Lengthening of Telomeres (ALT), which is a telomerase-independent telomere maintenance mechanism. Intriguingly, SLX4IP interacts with the heterodimeric structure-specific endonuclease ERCC1-XPF, which cleaves the 3′ flaps of DNA intermediates that occur during several DNA repair pathways and also as a consequence of telomere maintenance. The physiological importance of ERCC1-XPF is underscored by the fact that inactivating mutations in XPF are associated with several genome instability syndromes. In addition, ERCC1-XPF is essential for kidney homeostasis and its loss leads to glomerular aging and renal fibrosis. To date, it remains entirely unclear why and how SLX4IP interacts with ERCC1-XPF and how this interaction relates to the cellular and physiological functions of this endonuclease. The objectives of this research proposal are, thus, to understand how SLX4IP regulates ERCC1-XPF function to ensure telomere stability and to elucidate the physiological consequences of a dysfunctional SLX4IP-ERCC1-XPF module. Specifically, we propose to characterize the molecular relationship of SLX4IP and ERCC1-XPF, to investigate how SLX4IP modulates ERCC1-XPF telomere functions, and to understand the consequences of a dysfunctional SLX4IP-ERCC1-XPF module on general genome maintenance and on organ homeostasis using mouse kidney fibrosis as model system.
X: FOR5504 reposted Björn Schumacher (@schumacherbj)
2nd Meeting on Epigenetics & Epigenomics in Health & Disease, Brussels, 25-26 Sept.2025
Angelina Job Kolady on being selected to present her work...
Angelina Job Kolady has been selected to present her ongoing PhD work as a poster at the 2nd Meeting on Epigenetics & Epigenomics in Health & Disease, Brussels, 25-26 Sept.2025.
Angelina Job Kolady:
"It was a pleasure to be selected to present my ongoing PhD work as a poster at the 2nd Meeting on Epigenetics & Epigenomics in Health & Disease, held in Brussels from 25 to 26 September 2025. The conference provided me a platform to share my work, exchange scientific ideas, and receive constructive feedback from the epigenetics community across the globe.
A key opportunity was to receive direct feedback from Bernd Pulverer, the chief editor of EMBO Reports and discuss the project.
The pre-conference Science Gateway session (24 September 2025) was highly valuable, and the structured “speed-dating”-style interactions with leaders in epigenetics gave me a chance to discuss both fundamental research and translational applications.
I am grateful to the organisers of the conference and my supervisors, Siyao Wang and Björn Schumacher, for their continuous support and encouragement. I am looking forward to implementing the received insights and discussions in the next steps of my PhD."
X: FOR5504 reposted Robert Hänsel-Hertsch (@EpiStrucStab)
Tahira Aslan receives Oral Communication Prize of the Biochemical Society
The whole FOR5504 warmly congratulates Tahira Aslan on being awarded
Oral Communication Prize of the Biochemical Society for Tahira Aslan.
Congratulations to Tahira Aslan for the Oral Communication Prize of the Biochemical Society at the 92nd Harden Conference on Germ Cell Biology
Dr. Siyao Wang receives FEBS Excellence Award
The whole FOR5504 warmly congratulates Dr. Siyao Wang on being awarded the prestigious FEBS Excellence Award, recognizing outstanding contributions to molecular life sciences.
The whole FOR5504 warmly congratulates Dr. Siyao Wang on being awarded the prestigious FEBS Excellence Award, recognizing outstanding contributions to molecular life sciences.
FEBS Excellence Award for Siyao Wang
The father contributes nearly 80% of germline de novo mutations (DNMs) compared to the mother. While germline DNMs drive genetic diversity during evolution, they are also a fundamental cause of genetic disorders in offspring. Although it was written in the textbook that the paternal germline DNMs mainly arise from replication errors, emerging evidence suggests that many are due to errors in DNA damage repair. Aging is a common risk factor for paternal germline DNA damage due to increased intrinsic genotoxic attacks. Studies indicate that advanced paternal age is associated with a higher rate of germline DNMs and an increased incidence of schizophrenia and autism in progeny.
Wang’s group studies the molecular mechanism underlying the inheritance of paternal DNA damage response. By elucidating the mechanism, this work will provide insight into male-derived genetic diversity in evolution.
About the FEBS Excellence Award
The Federation of European Biochemical Societies (FEBS) launched the Excellence Awards scheme from 2021, it supports early-career group leaders in the FEBS area who have a scientific research track record of proven excellence. FEBS Excellence Awards provide funding of €100,000 for research equipment and consumables over a 3-year period.
X/Twitter: @schumacherbj
Huge congrats to
for receiving the Best Poster award
2024. Well deserved for his outstanding work
Epigenetic Regulation of Cellular Homeostasis Amid Transcription-Blocking DNA Damage During Development and Aging, project 3
Epigenetic Regulation of Cellular Homeostasis Amid Transcription-Blocking DNA Damage During Development and Aging, project 3
The research project focuses on how epigenetic mechanisms, particularly the deposition of H3K4me2 by the MLL/COMPASS complex, are regulated in response to transcription-blocking DNA damage. It investigates how this histone modification aids in the recovery of transcription elongation and the maintenance of cellular homeostasis during both development and aging. Using *C. elegans*, the study seeks to understand the physiological consequences of genome instability, particularly how impaired or enhanced deposition of H3K4me2 influences growth and longevity .
"Mechanical-stress induced DNA damage and genome mechanoprotection in cellular and organismal homeostasis", (project 2)
"Mechanical-stress induced DNA damage and genome mechanoprotection in cellular and organismal homeostasis", (project 2)
The nematode C. elegans is an excellent in vivo model system for DNA damage and repair responses. To understand the role of mechanical forces as physiological trigger of DNA damage in live animals, we will visualize and quantify relationships between nuclear deformation and DNA damage and analyze its functional consequences of organismal function, focusing on the highly dynamic C. elegans germline.
"Mechanism and Consequences of SLX4IP- and ERCC1-XPF-dependent Telomere Dysfunction", project 6
project leader: Stephanie Panier
Somatic cells have finite replicative lifespans because telomeres undergo progressive shortening after DNA replication, which can lead to genome instability and induce senescence. Telomere dysfunction has profound physiological consequences and promotes the accelerated development of many age-associated pathologies such as tumorigenesis and kidney disease. We have previously described the adapter protein SLX4IP as an important regulator of recombination-based Alternative Lengthening of Telomeres (ALT), which is a telomerase-independent telomere maintenance mechanism. Intriguingly, SLX4IP interacts with the heterodimeric structure-specific endonuclease ERCC1-XPF, which cleaves the 3′ flaps of DNA intermediates that occur during several DNA repair pathways and also as a consequence of telomere maintenance. The physiological importance of ERCC1-XPF is underscored by the fact that inactivating mutations in XPF are associated with several genome instability syndromes. In addition, ERCC1-XPF is essential for kidney homeostasis and its loss leads to glomerular aging and renal fibrosis. To date, it remains entirely unclear why and how SLX4IP interacts with ERCC1-XPF and how this interaction relates to the cellular and physiological functions of this endonuclease. The objectives of this research proposal are, thus, to understand how SLX4IP regulates ERCC1-XPF function to ensure telomere stability and to elucidate the physiological consequences of a dysfunctional SLX4IP-ERCC1-XPF module. Specifically, we propose to characterize the molecular relationship of SLX4IP and ERCC1-XPF, to investigate how SLX4IP modulates ERCC1-XPF telomere functions, and to understand the consequences of a dysfunctional SLX4IP-ERCC1-XPF module on general genome maintenance and on organ homeostasis using mouse kidney fibrosis as model system.
ADP-ribosylation, DNA strand breaks and human disease
Seminar talk by Dr. Hana Hanzlikova from University of Bern and Institute of Molecular Geneticsof the Czech Academy of Sciences (Prague).
We investigate the mechanisms that preserve genome integrity, focusing on DNA single-strand break repair and ADP-ribosylation mediated by the PARP1 and PARP2 enzymes. This seminar will highlight how defects in DNA repair pathways and dysregulated ADP-ribosylation are associated with cancer and neurological disease. We will also discuss the molecular basis of PARP inhibition, offering insights into how a detailed understanding of ADP-ribosylation at sites of DNA damage can guide the development of more effective therapeutic strategies.
Gametes with damaged DNA: how does the embryo react?
Seminar talk by Dr. Tommaso Cavazza from University Zurich
Physical exclusion of heterochromatin at nuclear pores maintain global chromatin organization
title: Physical exclusion of heterochromatin at nuclear pores maintain global chromatin organization
Seminar talk by Dr. Charléne Boumendil from CNRS- Institute of Human Genetics, UMR 9002.
In eukaryotic cells, the genetic material - the DNA, stored in the nucleus is facing two major challenges: (i) there are different subcompartments in the nucleus (ii) it is organized as a nucleo-protein complex in the form of chromatin. These two levels can potentially contribute to modulate all genome functions.
Our lab is interested in understanding how these two levels of nuclear architecture (nuclear compartments and chromatin organization) cooperate to allow the regulation of DNA functions such as DNA repair or gene expression. As an example, while the nuclear lamina usually associates with compact chromatin, called heterochromatin, the nuclear pores are always devoid of heterochromatin association. We recently showed that nuclear pores density increase can trigger major chromatin rearrangements during cellular senescence, which correlates with the expression of a specific inflammatory gene network.
We use a variety of approaches including cellular and molecular biology, advanced imaging methods and synthetic biology in various cellular models, including cellular senescence and mouse embryonic stem cells.
Kölner Stadtanzeiger: Warum Herr Malsam immer noch lebt
Die Zulassung der Immuntherapie mit CAR-T-Zellen kam gerade rechtzeitig, um einem Patienten der Uniklinik Köln das Leben zu retten.
Die Zulassung der Immuntherapie mit CAR-T-Zellen kam gerade rechtzeitig, um einem Patienten der Uniklinik Köln das Leben zu retten.
Als der Blutbeutel die Uniklinik verlässt, weichen Jörg Malsams Gedanken nicht mehr von seiner Seite. 35 Tage bis zur Rückkehr. Im Kopf fährt und fliegt er mit, fürchtet widrige Verkehrsbedingungen, die die gekühlte Fracht im Gepäckraum überstehen muss. Denkt an seine Zellen, wie sie bearbeitet werden. Wie sie schließlich – wieder mit raumgreifendem Isolationsmaterial ummantelt – die Rückreise antreten. Im Kopf der Gedanke, der alles andere an den Rand verdrängt: „Wenn der Kurier einen Autounfall hat, was dann?“
Jörg Malsam sitzt in der Uniklinik Köln.
...
Bild Copyright: Alexander Schwaiger
Bild der Wissenschaft PODCAST – Folge 24: Longevity
Podcast: https://www.wissenschaft.de/gesundheit-medizin/bdw-podcast-folge-24/
Wie gelingt es, nicht nur länger, sondern vor allem länger gesund zu leben? Björn Schumacher vom Institut für Genomstabilität bei Alterung und Erkrankung an der Universität zu Köln erklärt, welche Rolle das Erbgut und unser Lebensstil dabei spielen.
DIE GROSSEN FRAGEN DER WISSENSCHAF: Können wir ewig leben, Björn Schumacher?
Article und Podcast: https://www.spektrum.de/news/longevity-koennen-wir-ewig-leben-bjoern-schumacher/2301110
Interview: Die großen Fragen der Wissenschaft von Carsten Könneker und Katharina Menne
Frage: Können wir ewig leben, Björn Schumacher?
Björn Schumacher erforscht, wie Menschen möglichst lange gesund leben. Ein Gespräch über »Altersuhren«, Fadenwürmer, den Traum von der ewigen Jugend und die richtige Medizin.
Im Podcast »Die großen Fragen der Wissenschaft« gehen wir den größten Rätseln des Universums auf den Grund. Dieses Interview ist eine gekürzte und angepasste Fassung der Folge »Können wir ewig leben, Björn Schumacher?«.
Dual modification activates BRCA2 for RAD51 assembly
title: Dual modification activates BRCA2 for RAD51 assembly
Seminar talk by Dr. Puck Knipscheer from Hubrecht Institute.
The Knipscheer group studies molecular mechanisms of DNA replication and repair.
Cellular processes that maintain the integrity of our genome are crucial to prevent genetic diseases such as cancer. The main interest of our laboratory is to decipher the molecular details of these processes. Currently, we focus on understanding how toxic DNA lesions, called interstrand crosslinks (ICLs), are repaired, and how stable secondary DNA structures (G-quadruplexes) are resolved. We study these processes in the context of active DNA replication and make use of Xenopus egg extracts that support highly regulated vertebrate DNA replication in vitro. In this experimental system, we can recapitulate both ICL repair and G-quadruplex replication in a test tube, allowing us to gain insights in their molecular mechanisms.
"Genome Instability Syndromes as a Toolbox to Unravel Novel DNA Repair Pathways", (project 5)
We aim to explore the causes and consequences of deregulated DNA repair to explain important phenotypes observed in our novel human genome instability syndromes. Importantly, these insights will serve as a blueprint to understand the intricate relationship between the DDR, protein homeostasis and neurodegeneration.
Understanding BRCA1 protein complexes in health and disease
"Understanding BRCA1 protein complexes in health and disease"
Seminar talk by Dr. Sylvie Noordermeer from Leiden University Medical Center.
In our lab we are interested in how BRCA1 protein complexes coordinate the essential roles of this tumour suppressor gene in genome stability maintenance. In the first part of my talk, I will present a study in which we profiled how the C-terminal BRCT domains of BRCA1 bind to three mutually exclusive protein complexes and how disruption of binding to individual complexes affects BRCA1’s role in homologous recombination. In the second part, I will present an ongoing project to better understand the mechanistic role of BRCA1’s exon 11, encoding for ~60% of the protein. Via proteomic approaches, we have found novel interactors to this domain that are involved in regulating DNA end-resection.
"Epigenetic determinants of genome stability for mammalian tissue", (project 1)
"Epigenetic determinants of genome stability for mammalian tissue", (project 1)
This project will elucidate epigenetic mechanisms promoting genome instability when tissue homeostasis declines with age and under physiological stress. We discovered elevated G– quadruplex (G4) DNA secondary structure formation in mutated highly transcribed gene regulatory regions of cancer, suggesting dysregulated G4s as promoter of genome instability. We have and continue to gather evidence that dysregulated G4s emerge before cancer development in physiologically aged murine tissues and rapidly aged murine and human models. We hypothesize here that dysregulated G4 secondary structure formation may promote genome instability and heterostasis in aged and stress-induced rodent tissues. By exploiting our newly developed multiomics technology to jointly map epigenetically linked DNA breakage landscapes, beyond association, we will identify epigenetic mechanisms that critically drive persistent and/or elevated DNA breakage. To identify epigenetic regulators that promote an increase in epigenetically linked DNA breakage in tissues of our rodent models, we will use computational predictions and experimental associations of our multiomics data with existing data sets. We will use proximity ligation proteomics of tissue-derived nuclei to directly link regulatory factors to epigenetically linked DNA breakage and validate these findings by genetic loss-of-function in C. elegans.
ZDF Volle Kanne - Längeres Leben durch Trend Longevity?
"Longevity" bedeutet Langlebigkeit und ist längst zu einem Internet-Trend geworden.
Watch his interview:
https://www.zdfheute.de/video/volle-kanne/longevity-was-ist-dran-100.html
Show: ZDF - Volle Kanne
Thema: Längeres Leben durch Trend Longevity?
"Longevity" bedeutet Langlebigkeit und ist längst zu einem Internet-Trend geworden. Wie effektiv sind die Maßnahmen, die Anhänger dieser Bewegung verfolgen? Biologe Prof. Björn Schumacher im Gespräch.
Shaping the genome with diet: how nutritional cues influence chromatin organization and function in a whole organism
title: Shaping the genome with diet: how nutritional cues influence chromatin organization and function in a whole organism
Seminar talk by Dr. Daphne S. Cabianca from Helmholtz Zentrum, Munich.
Dr. Daphne S. Cabianca leads the Environment and Nuclear Organization group at Helmholtz Munich’s Institute of Functional Epigenetics. Her research focuses on how environmental cues—such as temperature or nutrient availability—reshape chromatin organization and gene expression. Using C. elegans as a model, her team combines CRISPR-based genome engineering, live imaging, and sequencing approaches to uncover how spatial chromatin dynamics contribute to cellular adaptation.
"Aging in the hematopoietic compartment" (Kirschner) and "Beyond clocks - the inner workings of DNA methylation dynamics" (Chandra)
seminar talks:
Aging in the hematopoietic compartment (Kirschner)
Beyond clocks - the inner workings of DNA methylation dynamics (Chandra)
Dr. Kirschner’s lab deciphers how age‑driven alterations in hematopoietic stem cells fuel blood cancer risk. Her pioneering work combines single‑cell multiomics with population studies to build predictive tools for clonal hematopoiesis and explore senescence dynamics—advancing strategies to intercept age‑related disease
Dr. Chandra’s interdisciplinary research harnesses genomics, AI, and quantitative biology to unravel the molecular basis of epigenetic aging, senescence, and clonal mosaicism. His team probes how epigenetic clocks may be reset via partial reprogramming in blood, and applies AI-driven tools to stratify patient risk and rejuvenate aging phenotypes.
"Mechanical-stress induced DNA damage and genome mechanoprotection in cellular and organismal homeostasis", (project 2)
"Mechanical-stress induced DNA damage and genome mechanoprotection in cellular and organismal homeostasis", (project 2)
The nematode C. elegans is an excellent in vivo model system for DNA damage and repair responses. To understand the role of mechanical forces as physiological trigger of DNA damage in live animals, we will visualize and quantify relationships between nuclear deformation and DNA damage and analyze its functional consequences of organismal function, focusing on the highly dynamic C. elegans germline.
A single PAF1C subunit guides RNA polymerase II from elongation to transcription-coupled DNA repair by stabilizing CSB
title: tba
Seminar talk by Dr. Martijn S. Luijsterburg from Leiden University Medical Center.
Dr. Martijn S. Luijsterburg (Leiden University Medical Center) will present recent work on the molecular mechanisms underlying transcription-coupled DNA repair. His research combines genetic, genomic, and proteomic approaches to study how cells recognize and process DNA damage that interferes with transcription. The seminar will highlight new insights into the coordination between transcription, chromatin remodeling, and DNA repair pathways.
Altersforscher klärt auf: Können wir unsere biologische Uhr zurückdrehen? | Prof. Björn Schumacher
"In dieser Episode spreche ich mit Prof. Björn Schumacher, Direktor des Instituts für Genomstabilität bei Alterung und Erkrankung am CECAD-Forschungszentrum der Universität Köln. Unser Thema: die Biologie des Alterns...."
Listen to his interview on Youtube: https://www.youtube.com/watch?v=GsHEJwgG6k4
Host: Modern Medicine mit Alessandro Falcone
Description:
"In dieser Episode spreche ich mit Prof. Björn Schumacher, Direktor des Instituts für Genomstabilität bei Alterung und Erkrankung am CECAD-Forschungszentrum der Universität Köln. Unser Thema: die Biologie des Alterns. Was passiert in unserem Körper, wenn wir älter werden – und was können wir aktiv tun, um diesen Prozess positiv zu beeinflussen? Neben bewährten Lebensstilfaktoren rücken zunehmend auch gezielte Interventionen wie Medikamente oder Nahrungsergänzungsmittel in den Fokus der Forschung.
In dieser Folge erfährst du:
✅ Was beim Altern auf zellulärer Ebene wirklich passiert
"DNA Damage Tolerance: Physiological and Cancer Therapeutic Relevance"
DNA Damage Tolerance: Physiological and Cancer Therapeutic Relevance
Seminar talk by Dr. Heinz Jacobs from Netherlands Cancer Institute Antoni Van Leeuwenhoek.
DNA Damage Tolerance is Essential for Hematopoietic Stem Cell Maintenance and Mammalian Life
Stem cells are key players in central biological processes, such as tissue homeostasis, ageing, and cancer formation. Stem cell depend on genome maintenance to prevent disease formation. DNA damage tolerance (DDT) pathways enable DNA replication in the presence of replication impediments and are regulated by PCNAK164 ubiquitination and REV1. The failure to generate PcnaK164R/K164R;Rev1-/- deficient mice revealed DDT as essential for mammalian life. The compound mutation rendered hematopoietic stem cells (HSCs) and the hematopoietic precursors genetically unstable, instigating a pathological process where the associated HSC depletion culminated in a severe, embryonic-lethal anemia. Single cell RNA-sequencing of the remaining HSCs and progenitors identified CD24Ahigh and CD93low erythroid-biased progenitors (EBP) within the Lineage-, Sca1+, cKit- (LSK) population. In line, this subset was found to depend on the erythroid transcription factor Klf1. In conclusion, DDT is an essential activity within the DNA damage response network and in maintaining HSC fitness. By studying this system, we identified an erythroid-biased progenitor subset within the LSK compartment.
A damage driven transcription stress on aging and the effect of calorie restriction, (project 7)
A damage driven transcription stress on aging and the effect of calorie restriction, project 7
Joris investigates how chronic genome instability disrupts tissue homeostasis, focusing on transcriptional stress and its systemic impacts during aging. Using progeroid DNA-repair-deficient mouse models, he revealed that transcriptional stalling induces metabolic dysfunction and accelerates tissue degeneration, including neurodegeneration. His groundbreaking discovery of dietary restriction as a therapy shows it mitigates DNA damage, reprograms metabolism, and significantly extends lifespan, offering a translational approach to aging-related diseases.
"Mechanical-stress induced DNA damage and genome mechanoprotection in cellular and organismal homeostasis", (project 2)
Sara and Anja are investigating how mechanical stress leads to DNA damage and affects genome mechanoprotection in cellular and organismal homeostasis. Their work focuses on uncovering the mechanisms through which physical forces trigger chromatin changes, replication stress, and DNA damage. This project aims to enhance our understanding of the role of mechanical stress in genome stability and its broader implications for tissue functionality.
Silent but deadly telomere interactions in cancer cells
"Silent but deadly telomere interactions in cancer cells"
Seminar talk in cooperation with the Cologne Graduate School of Ageing Research (CGA).
Dr. Roderick O'Sullivan's research at UPMC Pittsburgh focuses on understanding how telomeres, the protective caps at the ends of chromosomes, maintain genome stability. His lab investigates the proteins that regulate telomere structure and function, particularly within the Alternative Lengthening of Telomeres (ALT) pathway, which is implicated in certain cancers. By studying chromatin dynamics and DNA repair mechanisms at telomeres, O'Sullivan aims to uncover how telomere dysfunction can lead to genomic instability, a hallmark of cancer. His research also explores how modifications like poly-ADP-ribosylation impact telomere maintenance and cellular aging.
"Uncovering the link between mitochondrial dynamics and chromosome segregation", (affiliated group leader)
Uncovering the link between mitochondrial dynamics and chromosome segregation
Defects in mitotic progression can result in aneuploidy, cell death, and morphological abnormalities in daughter cells, often arising from improper organelle segregation, as demonstrated for the endoplasmic reticulum and Golgi. However, the impact of defective mitochondrial dynamics on mitotic progression, chromosome inheritance, and their broader physiological consequences remains largely overlooked, particularly in the context of mitochondrial diseases and aging. Our group is currently exploring the hypothesis that MTX2 plays a critical role in mitochondrial segregation during mitosis. Pathogenic mutations of MTX2, linked to a mitochondrial form of progeria, may disrupt this process, leading to mitotic errors that contribute to disease progression. Understanding these mechanisms could provide key insights into the interplay between mitochondrial dysfunction, mitotic defects, and aging-related disorders.
"The role of the DNA damage response in renal ciliopathies"
While humans and house mice develop kidney failure upon injury, the spiny mouse has a unique mechanism to repair kidney injury and prevent concomitant permanent kidney failure. My aim is to decipher the unique regenerative capacity by identifying the master switches which are repressed in humans and house mice by using tubuloids of spiny mice. The master switches can be targets in future regenerative medicine applications.
"Two cell cycle regulatory protein families: from functional studies to their use as novel diagnostic markers and therapeutic targets in cancer"
guest: Prof. Jörg Kobarg (University of Campinas)
Cancer is among the diseases that most kill humans and domestic animals. Depending on the tissue and cell type affected by mutations, a large number of sub-types of cancer can be differentiated. For a specific sub-type of cancer the molecular causes can be quite heterogeneous and for the majority of cases are poorly mapped. This represents both a major challenge as well as an opportunity in the field, since an intense study of the molecular causes can lead to new diagnostic and therapeutic strategies. Protein kinases in signaling pathways and regulatory proteins in general, are frequently affected by activating or inactivating mutations in cancer and therefore contribute to cancer transformation. We study two families of proteins with great potential of utility for both diagnostic and therapy in cancer. For the Nek family of serine/threonine protein kinases we focus on: Nek1,4,5,6,8, and 10, which are involved in the regulation of the cell cycle, mitosis, primary cilia function, DNA repair mechanisms and mitochondrial functions. The second family comprises the two human regulatory proteins, called HABP4 and SERBP1, that have roles in the regulation of transcription and gene expression, cell proliferation and the cell's responses to stress. Gene knock out studies and functional cellular and biochemical assays showed a new functional axis for the Nek kinases in the regulation of mitochondrial morphology and respiration. In case of the HABP1/SERBP1 regulatory proteins, molecular biology studies over the years point to a role in the regulation of mRNA stability or turn over. Novel data highlight the potential of both protein families for improved cancer diagnostics/prognostics, and in case of the Nek family members, also as potential novel target proteins for small molecular inhibitors, in cancer.
Epigenetic Regulation of Cellular Homeostasis Amid Transcription-Blocking DNA Damage During Development and Aging, project 3
Epigenetic Regulation of Cellular Homeostasis Amid Transcription-Blocking DNA Damage During Development and Aging, project 3
The research project focuses on how epigenetic mechanisms, particularly the deposition of H3K4me2 by the MLL/COMPASS complex, are regulated in response to transcription-blocking DNA damage. It investigates how this histone modification aids in the recovery of transcription elongation and the maintenance of cellular homeostasis during both development and aging. Using *C. elegans*, the study seeks to understand the physiological consequences of genome instability, particularly how impaired or enhanced deposition of H3K4me2 influences growth and longevity .
MD fellowship project reports
MD Fellowship Project Presentations
Giuseppe Oppedisano and Lukas Koch were awarded the FOR5504 MD Fellowship in November 2023, receiving a one-year stipend to dedicate full-time efforts to their individual research projects.
• Giuseppe Oppedisano conducted his research in the workgroup of Dr. Miguel Angel Alejandre Alcázar (Department of Pediatric and Adolescent Medicine). His project, titled “Interplay of Early Life Obesity, Genome Stability, and the Risk for Cardiopulmonary Diseases through Adipocyte-Secreted Extracellular Vesicles (EVs),” investigates how obesity in early life may influence genome stability and elevate risks for cardiopulmonary conditions via signals transmitted by EVs from fat cells.
• Lukas Koch worked in the group of Prof. Dr. Carien M. Niessen at CECAD. His project, “The Role of Cell Polarity in Mitochondrial Dynamics and Cell Fate in Field Cancerization and Squamous Cell Carcinoma Formation,” explores how disruptions in cell polarity impact mitochondrial behavior and contribute to the development of cancerous fields and squamous cell carcinoma.
"Repair of DNA double-strand by non-homologous end-joining"
Prof. Dr. Markus Löbrich (TU Darmstadt)
DNA double-strand breaks (DSBs) are major lesions induced by ionizing radiation and other DNA damaging agents. The main pathway for repairing DSBs in non-replicating cells is non-homologous end-joining (NHEJ). My talk will address two questions. First, I will talk about how NHEJ repairs DSBs which arise in transcribed genomic regions. This question is particularly important for long-living cells such as post-mitotic neurons which need to maintain gene functionality over decades. Second, I will address the question of how cells repair DSBs at very low damage levels. Super low damage levels represent the physiologically relevant situation and our findings suggests a new mechanism of cancer avoidance under such circumstances.
"tba", central project (Z) 1
"tba", (central project 1)
A computational platform for data support, integration and management
The Research Unit will generate large amounts of OMICS data. These data require powerful and sophisticated analyses. The Z1 project will support analysis, data integration within and among the individual projects as well as management to ensure efficient usage and reproducibility of the data among the Research Unit members. It will assist in planning OMICS experiments, for example, the design of technical and biological replicates and experimental blinding strategies. In addition, it will also provide training to members of the Research Unit to empower researchers to interrogate their own data and to properly document their work. The Z1 project leaders are experienced in generating and working with diverse and large-scale data types and are in a unique position to oversee and support this aspect of the Research Unit. The Z1 project will assist in the generation, selection, analysis, sustainable storage and usability of diverse OMICS data.
DNA Repair Meeting 2024 (DGDR)
Annual Meeting of the DGDR:
DNA Repair Meeting 2024
https://dgdr6.webnode.page/l/annual-dgdr-meeting/
September 25-27 | Cologne, Germany
Registration Deadline 30.6.24
Registration: :https://cms2.vcongress.de/dgdr-2024
joint FOR5504 retreat
Epigenetik – Prof. Dr. Björn Schumacher über epigenetische Uhren und die epigenetische Alterung
"In diesem Podcast spreche ich mit Prof. Dr. Björn Schumacher über den Forschungsstand von epigenetischen Uhren."
Listen to his interview on Youtube: https://www.youtube.com/watch?v=KVF_N2a3IjM
Host: staYoung - Der Longevity-Podcast (von Nina Ruge)
Description:
In diesem Podcast spreche ich mit Prof. Dr. Björn Schumacher über den Forschungsstand von epigenetischen Uhren. Prof. Dr. Schumacher ist Direktor des Instituts für Genomstabilität bei Alterung und Erkrankung am CECAD-Forschungszentrum der Uni Köln. Er sagt: „Nur wenn wir den Alterungsprozess verstehen, wird es uns gelingen Alterskrankheiten wirksam zu verhindern und ein gesundes Altern zu ermöglichen.“ In dieser Folge behandeln wir folgende Fragen:
"AGE-RELATED LOSS OF HETEROCHROMATIN IN OOCYTES AND GRANULOSA CELLS AND ITS ASSOCIATED FERTILITY OUTCOMES"
Guest: Dr. Michael Klutstein, The Chromatin and Aging Research Lab (CARL), The Hebrew University of Jerusalem
"Mechanism of genetic quality control in germ cells"
Guest: Dr. Volker Dötsch, Goethe-Universität Frankfurt
The survival rate of cancer patients is steadily increasing due to better and more efficient therapies. These advances in cancer therapy, however, create a new and increasing problem since treatment with chemotherapeutic drugs and radiation increases the risk of premature ovarian insufficiency (POI) for female cancer patients. While assisted reproductive technologies can address the problem of infertility, these measures cannot restore the hormonal functions pivotal for women’s health. Although recent advances in whole organ replacement could eventually offer an option to restore long-term hormone function and fertility in the future, a more detailed understanding of the molecular mechanisms of therapy-induced POI could identify targets for pharmacological prevention of POI during gonadotoxic therapies. Loss of the primordial follicle reserve is the most important cause of POI. TAp63a, a member of the p53 family, is the central transcription factor that upregulates the apoptotic program in oocytes. In resting primary oocytes it adopts an inactive state by forming a closed, only dimeric conformation. Detection of DNA damage activates the stress kinases CHk1 and CHk2 which leads to the phosphorylation of TAp63a which itself does not influence the conformation of TAp63a. Instead it recruits another kinase, CK1, which adds four more phosphate groups C-terminally to the CHk2 site. Electrostatic repulsion between the phosphate groups and a stretch of aspartic acids results in the destabilization of the closed dimeric state and the formation of the open and active tetramer. Measuring the phosphorylation kinetics has further shown that the individual CK1 phosphorylation events follow different kinetic regimes which is part of a kinetically encoded safety mechanism that triggers oocytes death only if a certain DNA damage level threshold is reached. This sophisticated system of monitoring the genetic integrity is evolutionary highly conserved but absent in male germ cells.
"Unravelling the role of RPA4 in genome stability using the naked mole-rat physiology."
"Unravelling the role of RPA4 in genome stability using the naked mole-rat physiology.", (FOR5504 - start-up funded postdoc)
The similarities between human replication protein A complex (RPA4) and naked mole rat (NMR) RPA4 (hgRPA) (62% protein identity) make the NMR an intriguing model for investigating aRPA function in vitro and in vivo. The RPA4 single-stranded DNA binding and winged-helix domains are also present in NMR (Ensembl and NCBI). Studying RPA4 in NMR could provide valuable insights into its contribution to genome stability, potentially shedding light on the remarkable healthspan and longevity of this unique rodent species.
Hence, with my independent project I aim to study three major points:
"ADP-ribosylation at the nuclear pore complex"
"ADP-ribosylation at the nuclear pore complex", (FOR5504-associated group leader)
'Talk less, say more'
trainer: Max Moenikes
In the pursuit of gender equality and equal opportunities in science, effective communication plays a pivotal role. This workshop is designed to empower individuals, with a particular focus on promoting and advancing women in science, by enhancing their rhetorical and communicative skills. In academic and professional settings, individuals often encounter speaking engagements ranging from team meetings and conferences to thesis presentations, funding applications, and teaching roles. While these opportunities can be exciting, they may also evoke feelings of stage fright and stress. However, with proper practice and preparation, anyone can confidently navigate these situations. In this seminar, we aim to cultivate essential rhetorical skills in a practical and engaging manner, recognizing the unique challenges faced by women in science. Our primary objective is to foster harmonious interactions among body language, voice, and content, enabling participants to authentically embody their intentions and garner approval from their audience.
The seminar curriculum is structured around the three fundamental pillars of rhetoric:
1) Body Language: Participants will learn to leverage posture, gestures, facial expressions, and eye contact for effective communication, creating a confident and impactful presence
2) Voice: Emphasis will be placed on techniques such as breathing, volume control, intonation and articulation, enabling participants to amplify their voices and convey their messages with clarity
3) Content: Strategies for structuring and planning speeches, as well as mastering argumentation techniques, will be explored, empowering participants to articulate their ideas persuasively
"Using CRISPR screens to map genetic determinants of radiation response."
Guest: Dr. Graeme Hewitt, CRUK RadNet Jr Group Leader
Aging clocks are based on random events / publication in ‘Nature Aging’ feat. Prof. Björn Schumacher and David Meyer
Scientists David Meyer and Professor Dr Björn Schumacher at CECAD, the Cluster of Excellence Cellular Stress Responses in Aging-Associated Diseases of the University of Cologne, have now discovered that aging clocks actually measure the increase in ...
News article about Aging clocks, featuring Prof. Dr. Schumacher and David Meyer.
Aging clocks can measure the biological age of humans with high precision. Biological age can be influenced by environmental factors such as smoking or diet, thus deviating from the chronological age that is calculated using the date of birth. The precision of these aging clocks suggests that the aging process follows a programme. Scientists David Meyer and Professor Dr Björn Schumacher at CECAD, the Cluster of Excellence Cellular Stress Responses in Aging-Associated Diseases of the University of Cologne, have now discovered that aging clocks actually measure the increase in stochastic changes in cells. The study ‘Aging clocks based on accumulating stochastic variation’ has been published in Nature Aging.
Read the full article: https://www.cecad.uni-koeln.de/outreach/news/article/how-aging-clocks-tick/
"Mechanical-stress induced DNA damage and genome mechanoprotection in cellular and organismal homeostasis", (project 2)
"Mechanical-stress induced DNA damage and genome mechanoprotection in cellular and organismal homeostasis", (project 2)
The nematode C. elegans is an excellent in vivo model system for DNA damage and repair responses. To understand the role of mechanical forces as physiological trigger of DNA damage in live animals, we will visualize and quantify relationships between nuclear deformation and DNA damage and analyze its functional consequences of organismal function, focusing on the highly dynamic C. elegans germline.
"Epigenetic determinants of genome stability for mammalian tissue", (project 1)
"Epigenetic determinants of genome stability for mammalian tissue", (project 1)
This project will elucidate epigenetic mechanisms promoting genome instability when tissue homeostasis declines with age and under physiological stress. We discovered elevated G– quadruplex (G4) DNA secondary structure formation in mutated highly transcribed gene regulatory regions of cancer, suggesting dysregulated G4s as promoter of genome instability. We have and continue to gather evidence that dysregulated G4s emerge before cancer development in physiologically aged murine tissues and rapidly aged murine and human models. We hypothesize here that dysregulated G4 secondary structure formation may promote genome instability and heterostasis in aged and stress-induced rodent tissues. By exploiting our newly developed multiomics technology to jointly map epigenetically linked DNA breakage landscapes, beyond association, we will identify epigenetic mechanisms that critically drive persistent and/or elevated DNA breakage. To identify epigenetic regulators that promote an increase in epigenetically linked DNA breakage in tissues of our rodent models, we will use computational predictions and experimental associations of our multiomics data with existing data sets. We will use proximity ligation proteomics of tissue-derived nuclei to directly link regulatory factors to epigenetically linked DNA breakage and validate these findings by genetic loss-of-function in C. elegans.
"The Ins and Outs of Cellular Senescence: Mechanistic, Therapeutic, and Diagnostic Insights"
Cellular senescence is beneficial during embryonic development, wound healing, and tumor suppression. Paradoxically, it is also a significant contributor to aging and age-related diseases, including cancer. As such, research on therapeutic strategies targeting senescence to improve health span has gained enormous momentum in recent years. However, discovering therapeutic targets for such therapies is still challenging, as our understanding of the molecular mechanisms that execute and maintain the senescence phenotype is incomplete. This seminar will delve into recent breakthroughs in deciphering a major senescence clock and explore this knowledge's exciting therapeutic, prognostic, and diagnostic potential.
"Metabolic deregulation, genome instability, and the progression of chronic kidney disease", (project 8)
"Metabolic deregulation, genome instability, and the progression of chronic kidney disease", (project 8)
The major aim of this research proposal is to unravel the interplay of genome instability, epigenetic alterations, and metabolic deregulation in CKD pathogenesis. Kidney function depends on the bulk filtration of large volumes of water and small solutes to clear potential toxins that are derived from intracellular metabolism and gastrointestinal microbial metabolism, as well as to maintain salt and water and acid-base homeostasis. Even slight losses of kidney filtration function cause profound metabolic changes in the organism which may explain elevated risk for CKD progression, cardiovascular complications, and other comorbidities. Based on two well-established mouse models that show a CKD phenotype, we will provide mechanistic insight into genome instability as a driver of kidney disease progression and characterize metabolic, transcriptomic, and epigenetic alterations caused by DNA damage in the kidney. Moreover, we will analyze the effects of metabolic interventions on disease progression, with the ultimate goal to develop strategies for future clinical applications.
"Genome Instability Syndromes as a Toolbox to Unravel Novel DNA Repair Pathways", (project 5)
We aim to explore the causes and consequences of deregulated DNA repair to explain important phenotypes observed in our novel human genome instability syndromes. Importantly, these insights will serve as a blueprint to understand the intricate relationship between the DDR, protein homeostasis and neurodegeneration.
Unconscious Bias in Academia for PhD-students/Postdocs
In this Workshop you will get the opportunity to deal with problems of social perception and
its diverse biases. Based on bias research, we will explore consequences for academic
careers and cooperation with a focus on equal opportunities. You can put your own
perception to the test and discuss tools for dealing professionally with implicit bias as well as
more explicit forms of prejudice.
Unconscious Bias in Academia for Principal Investigations
In this Workshop you will get the opportunity to deal with problems of social perception and
its diverse biases. Based on bias research, we will explore consequences for academic
careers and cooperation with a focus on equal opportunities. You can put your own
perception to the test and discuss tools for dealing professionally with implicit bias as well as
more explicit forms of prejudice.
"The genetic basis and pleiotropic nature of human physical traits"
There are substantial within and between population variations in human physical traits (e.g. skin and hair morphology, cranial and facial features). Comparing to diseases, physical traits receive far less attention and are largely understudied. For more than 10 years, our team has been systematically studying human physical traits, aiming to elucidate the genetic factors underlying the within and between population variations, and to reveal the developmental and evolutionary mechanisms. We further investigate the association between human physical traits and diseases/wellness, exploring the mechanism of the pleiotropic effects, and constructing prediction models. In the future, we will also focus on the effects of environmental exposure factors on phenotypes and their interactions with the genetic factors. Our studies provide valuable examples of the human phenome research.
Website: http://www.picb.ac.cn/dermatogenomics
"Coordination of DNA Damage Response and Aging by Ubiquitin Signaling", project 4
The Science Breaker - Science meets Society
Mutations in the germline: How the mother repairs the father’s damaged genome
by Siyao Wang, David Meyer, Björn Schumacher
Germline mutations can have a severe impact on genetic diseases, genome evolution and the fate of a species. The vast majority of inheritable mutations are passed on by the paternal genome. We discovered how paternal DNA damage is repaired by maternal repair leading to the inheritance of structural variants.
Read the full article: https://www.thesciencebreaker.org/breaks/health-physiology/mutations-in-the-germline-how-the-mother-repairs-the-fathers-damaged-genome
FOR 5504
Universitätsklinik Köln
CECAD Research Center
Joseph-Stelzmann-Str. 26
50931 Köln
Tel. +49 (0)221 478 84198
simon.uszkoreit@uk-koeln.de
