A5007775756- Adenosine and Purinergic Signaling
- Synthesis and Biological Evaluation
- Pneumocystis jirovecii pneumonia detection and treatment
- Genetics and Neurodevelopmental Disorders
- Nanoplatforms for cancer theranostics
- Cancer Immunotherapy and Biomarkers
- Epigenetics and DNA Methylation
- Amoebic Infections and Treatments
- Parasitic Infections and Diagnostics
- Autism Spectrum Disorder Research
- Chromatin Remodeling and Cancer
- Immune Cell Function and Interaction
- Cancer-related gene regulation
- Genomic variations and chromosomal abnormalities
- Immune cells in cancer
- Peptidase Inhibition and Analysis
- Genomics and Chromatin Dynamics
- DNA Repair Mechanisms
- MicroRNA in disease regulation
- Cancer Research and Treatments
- Extracellular vesicles in disease
- Sirtuins and Resveratrol in Medicine
- Autophagy in Disease and Therapy
- PARP inhibition in cancer therapy
- S100 Proteins and Annexins
Dr Willmar Schwabe (Germany)
2023
Cornell University
2014-2022
Rockefeller University
2019-2020
Technical University of Darmstadt
2011-2019
Children's Cancer and Blood Foundation
2014-2016
Weill Cornell Medicine
2016
University Hospital Münster
2012-2014
Ludwig-Maximilians-Universität München
2007
Max Delbrück Center
2007
University of Münster
2004
There is increasing evidence of crosstalk between epigenetic modifications such as histone and DNA methylation, recognized by HP1 methyl CpG-binding proteins, respectively. We have previously shown that the level proteins increased dramatically during myogenesis leading to large-scale heterochromatin reorganization. In this work, we show isoforms did not change significantly throughout myogenic differentiation but their localization did. particular, HP1gamma relocalization correlated with...
Entamoeba histolytica causes amebic dysentery and liver abscess, major of morbidity mortality worldwide. We have used differential hybridization screening to isolate an E. histolytica-specific cDNA clone. The was found encode a serine-rich protein (SREHP) containing multiple tandem repeats. structural motif SREHP resembles some the repetitive antigens malarial species, especially circumsporozoite proteins. A recombinant trpE fusion repeats recognized by immune serum from patient with...
Rett syndrome is a neurological, X chromosomal-linked disorder associated with mutations in the MECP2 gene. MeCP2 protein has been proposed to play role transcriptional regulation as well chromatin architecture. Since mutant cells exhibit surprisingly mild changes gene expression, we have now explored possibility that may affect ability of bind and organize chromatin. We found all but one 21 missense mutants analyzed accumulated at heterochromatin about half them were significantly affected....
Abstract T cells play a critical role in the control of cancer. The development immune checkpoint blockers (ICB) aimed at enhancing antitumor T-cell responses has revolutionized cancer treatment. However, durable clinical benefit is observed only subset patients, prompting research efforts to focus on strategies that target multiple inhibitory signals within tumor microenvironment (TME) limit evasion and improve patient outcomes. Adenosine emerged as potent suppressant TME, CD73 major enzyme...
FK866 is a specific inhibitor of NAMPT and induces apoptosis leukemic cells by depletion intracellular NAD(+). Since up-regulation associated with several cases cancers, including leukemias, we asked whether in inhibition involves p53 pathway. We observed that induced reduced cell proliferation NB-4, OCI-AML3 MOLM-13 lines. In contrast, the leukemia lines, K-562 Kasumi, containing nonfunctional were relatively unaffected treatment. Importantly, direct sirtuins significantly viability...
Constitutive heterochromatin is considered as a functionally inert genome compartment, important for its architecture and stability. How such stable structure maintained not well understood. Here, we apply four different visualization schemes to label it investigate dynamics during DNA replication repair. We show that replisomes assemble over the in temporally ordered manner. Furthermore, undergoes transient decompaction locally at active sites of synthesis. Using selective laser...
We compared the adherence of E. histolytica trophozoites with a panel lectin-resistant CHO mutants altered glycosylation patterns. Our results coupled data from saccharide inhibition studies indicate that terminal N-acetyllactosamine units on Asn-linked complex type oligosaccharides provide major determinants cellular receptor for adhesion.
Heterochromatic regions represent a significant portion of the mammalian genome and have been implied in several important cellular processes, including cell division genomic stability. However, its composition dynamics remain largely unknown. To better understand how heterochromatin functions it is organized within context nucleus, we developed molecular tools allowing targeting virtually any nuclear factor specifically to heterochromatic and, thereby, manipulation, also temporally...
Epigenetic marks like methylation of cytosines at CpG dinucleotides are essential for mammalian development and play a major role in the regulation gene expression chromatin architecture. The methyl-cytosine binding domain (MBD) protein family recognizes translates this mark. We have recently shown that level MeCP2 MBD2, two members MBD family, increased during differentiation their ectopic induced heterochromatin clustering vivo. As oligomerization these proteins could constitute factor...
To study the relationship between carbohydrate-specific amebic cytoadherence and ameba-mediated cytotoxicity, we measured Entamoeba histolytica trophozoite-mediated cytolysis directed against a panel of four Chinese hamster ovary (CHO) cell lines that have defined alterations in their glycosylation patterns. We recently trophozoite adherence to this CHO cells showed trophozoites bind variant (RICR 15B), which are deficient Asn-linked N-acetyllactosamine units, at 12% level observed for...
Methyl CpG binding protein 2 (MeCP2) binds DNA, and has a preference for methylated CpGs and, hence, in cells, it accumulates heterochromatin. Even though is expressed ubiquitously MeCP2 particularly important during neuronal maturation. This underscored by the fact that Rett syndrome, neurological disease, 80% of patients carry mutation MECP2 gene. Since gene lies on X chromosome subjected to inactivation, affected are usually chimeric wild type mutant MeCP2. Here, we present generation...
Abstract Introduction: In the tumor micro-environment, extracellular ATP is sequentially hydrolyzed to adenosine by ecto-nucleotidases CD39 (ATP→AMP) and CD73 (AMP→adenosine). Adenosine, through activation of A2a receptor (A2aR), a potent inhibitor T-cell activation, resulting in an immunosuppressed phenotype. Thus, inhibition A2aR has recently generated great interest immuno-oncology. We present characterization novel, selective, highly small molecule antagonist which slated enter clinic...
Abstract TIGIT (T-cell immunoreceptor with Ig and ITIM domains) is an inhibitory receptor that expressed on natural killer (NK) cells, CD8+ T-cells, immunosuppressive regulatory T-cells (Treg). DNAM-1 (DNAX Accessory Molecule-1; CD226) activating found NK monocytes a subset of T-cells. are paired receptors compete for shared ligands CD155 (PVR) CD112 (Nectin-2) by tumor antigen-presenting cells. binding to or results in immune suppression, whereas the same mediates activation. As...
Humoral immunity in mammals relies on the function of two developmentally and functionally distinct B‐cell subsets—B1 B2 cells. While cells are responsible for adaptive response to environmental antigens, B1 regulate production polyreactive low‐affinity antibodies innate humoral immunity. The molecular mechanism specification into different subsets is understudied. In this study, we identified lysine methyltransferase NSD2 (MMSET/WHSC1) as a critical regulator cell development. contrast its...
Abstract INTRODUCTION: CD73 catalyzes the extracellular generation of adenosine (ADO) from monophosphate (AMP). ADO suppresses immune responses, including those T cells, NK cells and dendritic through activation A2aR A2bR receptors. Exhausted express high levels several checkpoint proteins, PD-1 TIGIT. We present here preclinical data on ability CD73i to reverse effector cell suppression exposure even in presence ICI. METHODS: effects a monotherapeutic setting were assessed by CD3/CD28/CD2...
Abstract Introduction: The intra-tumoral generation of adenosine (ADO), a potent inhibitor T-cell activation, depends on the coordinated and sequential cleavage extracellular triphosphate (ATP) by ecto-nucleotidases CD39 (which produces monophosphate, AMP) CD73 hydrolyzes AMP to form ADO). For this reason, number anti-CD73 antibodies are being advanced into clinical trials; however, date there have been few reports potent, selective, small-molecule inhibitors, such as those described here....
Abstract INTRODUCTION: In the tumor micro-environment (TME) Adenosine (ADO) dampens immune response towards cancer cells by inhibiting cytotoxic activity of effector and promoting proliferation immunosuppressive cells. Extracellular ADO is generated two ecto-nucleotidases CD39 (ATP→AMP) CD73 (AMP→ADO). signals primarily through G-protein coupled receptor A2aR. Inhibition generation signaling have been shown to be promising therapeutic approaches for treatment cancer. METHODS: Potent highly...