Juergen Kopitz

Juergen Kopitz
Universität Heidelberg · Institute of Pathology (Heidelberg)

About

256
Publications
18,255
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7,945
Citations
Citations since 2017
36 Research Items
2768 Citations
20172018201920202021202220230100200300400500
20172018201920202021202220230100200300400500
20172018201920202021202220230100200300400500
20172018201920202021202220230100200300400500

Publications

Publications (256)
Article
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Galectin-4 (Gal4) has been suggested to function as a tumor suppressor in colorectal cancer (CRC). In order to systematically explore its function in CRC, we established a CRC cell line where Gal4 expression can be regulated via the doxycycline (dox)-inducible expression of a single copy wildtype LGALS4 transgene generated by recombinase-mediated c...
Article
Mammalian galectins have no signal peptide, and it is not known what would happen if a galectin is directed to take the classical export route. The corresponding engineering of galectin-specific cDNA will answer questions on the fate of a signal peptide-bearing protein variant after its entry into the endoplasmic reticulum (ER). Affinity chromatogr...
Article
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A code is defined by the nature of the symbols, which generate information‐storing combinations (e.g. oligo‐ and polymers). Like nucleic acids and proteins, oligo‐ and polysaccharides are an ubiquitous platform for establishing molecular messages. An unsurpassed coding capacity is possible by variability in anomery and linkage positions of the glyc...
Article
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Wild-type lectins have distinct types of modular design. As a step to explain the physiological importance of their special status, hypothesis-driven protein engineering is used to generate variants. Concerning adhesion/growth-regulatory galectins, non-covalently associated homodimers are commonly encountered in vertebrates. The homodimeric galecti...
Article
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Rocaglates are natural compounds that have been extensively studied for their ability to inhibit translation initiation. Rocaglates represent promising drug candidates for tumor treatment due to their growth-inhibitory effects on neoplastic cells. In contrast to natural rocaglates, synthetic analogues of rocaglates have been less comprehensively ch...
Article
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Glycosylation is the most prevalent and varied form of post-translational protein modifications. Protein glycosylation regulates multiple cellular functions, including protein folding, cell adhesion, molecular trafficking and clearance, receptor activation, signal transduction, and endocytosis. In particular, membrane proteins are frequently highly...
Article
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The small 3-O-sulfated galactose headgroup of sulfatides, an abundant glycosphingolipid class, poses the (sphinx-like) riddle on involvement of glycan bridging by tissue lectins (sugar code). First, synthesis of headgroup derivatives for functionalization of amphiphilic dendrimers is performed. Aggregation of resulting (biomimetic) vesicles, alone...
Article
Full-text available
Human galectin-7 (Gal-7; also termed p53-induced gene 1 product) acts as a multifunctional effector by productive pairing with distinct glycoconjugates and protein counter-receptors in the cytoplasm and nucleus, as well as on the cell surface. Its structural analysis by NMR spectroscopy detected doubling of a set of particular resonances, an indica...
Article
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DNA mismatch repair-deficient colorectal cancers (CRCs) accumulate numerous frameshift mutations at repetitive sequences recognized as microsatellite instability (MSI). When coding mononucleotide repeats (cMNRs) are affected, tumors accumulate frameshift mutations and premature termination codons (PTC) potentially leading to truncated proteins. Non...
Article
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The emerging multifunctionality of galectins by specific protein-glycan/protein interactions explains the interest to determine their expression during embryogenesis. Complete network analysis of all seven chicken galectins (CGs) is presented in the course of differentiation of eye lens that originates from a single type of progenitor cell. It answ...
Article
Background: Galectins are multifunctional effectors, which all share absence of a signal sequence. It is not clear why galectins belong to the small set of proteins, which avoid the classical export route. Methods: Products of recombinant galectin expression in P. pastoris were analyzed by haemagglutination, gel filtration and electrophoresis an...
Article
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Ubiquitous occurrence in Nature, abundant presence at strategically important places such as the cell surface and dynamic shifts in their profile by diverse molecular switches qualifies the glycans to serve as versatile biochemical signals. However, their exceptional structural complexity often prevents one noting how simple the rules of objective-...
Article
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Microsatellite unstable (MSI) colorectal cancers (CRCs) are characterized by mutational inactivation of Transforming Growth Factor Beta Receptor Type 2 (TGFBR2). TGFBR2-deficient CRCs present altered target gene and protein expression. Such cellular alterations modulate the content of CRC-derived extracellular vesicles (EVs). EVs function as courie...
Article
Abstract Galectins are β-galactoside binding proteins which possess a variety of functions including modulation of apoptosis, growth and differentiation. Hence, alterations in the expression profile have been associated with loss of cellular homeostasis contributing to tumor growth and progression. Though galectin-12 is significantly downregulated...
Article
Full-text available
Tissue lectins appear to be involved in a broad range of physiological processes, as reflected for the members of the family of galectins by referring to them as adhesion/growth-regulatory effectors. In order to clarify the significance of galectin presence, key challenges are to define their binding partners and the profile of localization. Having...
Article
Background: Recognition of glycans by lectins is emerging as (patho)physiologically broadly used mode of cellular information transfer. Whereas the direct ligand-receptor contact is often already thoroughly characterized, the functional relevance of aspects of architecture such as modular design and valence of lectins is less well defined. Scope...
Article
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Significance Glycan-lectin recognition is vital to embryogenesis, and progression in common diseases such as cancer and osteoarthritis. However, the rules governing specificity for the functional pairing and postbinding events are not yet understood, even though human lectins have been thoroughly characterized structurally. Herein, we employ protei...
Article
Emerging evidence on efficient tumor growth regulation by endogenous lectins directs interest to determine on a proof‐of‐principle level the range of information on alterations provided by full‐scale analysis using phosphoproteomics. In our pilot study, we tested galectin‐4 (gal‐4) that is a growth inhibitor for colon cancer cells (CRC), here worki...
Article
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Delirium is a common complication seen after surgery and anesthesia, in particular in older patients. Although the etiology of postoperative delirium is only incompletely understood, various lines of evidence suggest that proinflammatory signaling from the peripheral site of inflammation to central nervous system results in a decrease of cerebral a...
Data
Supplementary table with blank corrected endpoint data.
Article
A higher capacity to grow under hypoxic conditions can lead to a more aggressive behavior of tumor cells. Determining tumor activity under hypoxia may identify chronic lymphocytic leukemia (CLL) with aggressive clinical course and predict response to chemo-immunotherapy (CIT). A metabolic score was generated by determining pyruvate kinase and lacta...
Article
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Acetylcholine is the main transmitter of the parasympathetic vagus nerve. According to the cholinergic anti-inflammatory pathway (CAP) concept, acetylcholine has been shown to be important for signal transmission within the immune system and also for a variety of other functions throughout the organism. The spleen is thought to play an important ro...
Article
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Smoking is associated with increased risk and poorer prognosis of pancreatic ductal adenocarcinoma (PDAC). Nicotine acts through cholinergic nicotinic receptors, preferentially a7 (CHRNA7) that also binds the endogenous ligand SLURP1 (Secreted Ly-6/uPAR-Related Protein 1). The clinical significance of SLURP1 and its interaction with nicotine in PDA...
Article
The delineation of the physiological significance of protein (lectin)-glycan recognition and the structural analysis of individual lectins have directed our attention to studying them in combination. In this report, we tested the hypothesis of hybrid formation by using binary mixtures of homodimeric galectins-1 and -7 as well as a proteolytically t...
Chapter
Molecular signals on the cell surface are responsible for adhesion and communication. Of relevance in this respect, their chemical properties endow carbohydrates with the capacity to store a maximum of information in a minimum of space. One way to present glycans on the cell surface is their covalent conjugation to a ceramide anchor. Among the resu...
Article
Galectins, a class of lectins with specificity for ß-galactoside containing glycoconjugates, modulate several cellular processes that are involved in the control of normal cell growth, differentiation, cell-cell, and cell matrix interactions. Pathological alterations of the galectin expression pattern have been implicated in the development and pro...
Article
Chemical and biological tools are harnessed to investigate the impact of spatial factors for functional pairing of human lectins with counterreceptors. The homodimeric adhesion/growth-regulatory galectin-1 and a set of covalently linked homo-oligomers from di- to tetramers serve as proof-of-principle test cases. Glycodendrimersomes provide a versat...
Article
Chemical and biological tools are harnessed to investigate the impact of spatial factors for functional pairing of human lectins with counterreceptors. The homodimeric adhesion/growth-regulatory galectin-1 and a set of covalently linked homo-oligomers from di- to tetramers serve as proof-of-principle test cases. Glycodendrimersomes provide a versat...
Article
Full-text available
Tissue lectins are emerging (patho)physiological effectors with broad significance. The capacity of adhesion/growth-regulatory galectins to form functional complexes with distinct cellular glycoconjugates is based on molecular selection of matching partners. Engineering of variants by changing the topological display of carbohydrate recognition dom...
Article
Full-text available
Background Colorectal cancers (CRCs) that lack DNA mismatch repair function exhibit the microsatellite unstable (MSI) phenotype and are characterized by the accumulation of frameshift mutations at short repetitive DNA sequences (microsatellites). These tumors recurrently show inactivating frameshift mutations in the tumor suppressor Transforming Gr...
Article
Background: The pathophysiological mechanisms of macular edema secondary to branch retinal vein occlusion (BRVO) remain unclear. Objectives: To analyze the protein profile of human vitreous of patients with BRVO and to identify specific dysregulated proteins. Materials and methods: Undiluted vitreous humor samples from patients with treatment...
Article
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Glycolipids are glycoconjugates that are predominantly found on the extracellular surface of cells ranging from bacteria to men. In bacteria and plants, glycoglycerolipids represent the main glycolipid species. Ceramides as carrier for glycans, termed glycosphingolipids (GSLs), are characteristic for vertebrates and insects. The glycan part is invo...
Chapter
Inactivating mutations in single genes can trigger, prevent, promote, or alleviate diseases. Identifying such disease-related genes is a main pillar of medical research. Since proteins play a crucial role in mediating these effects, their impact on the diseased cells’ proteome including posttranslational modifications has to be elucidated for a det...
Article
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Endogenous lectins have the capacity to translate glycan-encoded information on the cell surface into effects on cell growth. As test case to examine changes in protein presence associated with tumor growth inhibition, we applied SILAC-based proteomics on human colon carcinoma cells treated with galectin-4 (Gal-4). The five tested lines LS 180, Vac...
Article
Objective: The role of inflammation in cognitive alterations in a post-operative setting is still not fully understood. Surgical interventions can cause systemic inflammations which eventually can induce neuroinflammation. However, the main causes of functional changes after surgery are still elusive. In this study, we investigated the role of CD38...
Article
The potent multifunctionality of human galectins is based on their modular structure in a not yet fully understood manner. A strategy to dissect the contributions of individual sequence stretches to lectin activity is based on engineering variants of the natural proteins, which are composed of novel combinations of distinct parts. On proof-of-princ...
Article
Objective: The anticholinergic activity (AA) assay is a common method to determine a patient's anticholinergic load. Several limitations, however, are expected when applying the AA assay to patients or using drug scales to estimate anticholinergic burden based on AA levels. This study aims to demonstrate common pitfalls in an experimental setting...
Article
Context: Delirium is an important complication in palliative care patients. One of the potential risk factors for cognitive disorders is deterioration in cholinergic neurotransmission. Anticholinergic medications are known to be important owing to the association of their metabolites with significant morbidity, which is often the result of cumulat...
Article
Full-text available
Purpose: To analyze the protein profile of human vitreous of untreated patients with retinal vein occlusion (RVO). Methods: Sixty-eight vitreous humor (VH) samples (44 from patients with treatment naïve RVO, 24 controls with idiopathic floaters) were analyzed in this clinical-experimental study using capillary electrophoresis coupled to mass spe...
Data
Influence of past time period since suffering retinal vein occlusion on biomarker discovery. (DOCX)
Data
Epidemiology—detailed patient information. (DOCX)
Data
94 proteins being detected in vitreous humor. (DOCX)
Data
Subgroup analysis—detailed information. (DOCX)
Article
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Background Endogenous lectins are multifunctional effectors in cell physiology. Adding the sixth member of the galectin family in chicken, a model organism for systematic profiling of these adhesion/growth-regulatory proteins, is a step toward comprehensive network monitoring. Methods Database mining and computational data processing are applied fo...
Article
Occurrence of the adhesion/growth-regulatory galectins as family sets the challenge to achieve a complete network analysis. Along this route taken for a well-suited model organism (chicken), we fill the remaining gap to characterize its seventh member known from rat as galectin-related inter-fiber protein (GRIFIN) in the lens. Its single-copy gene...
Article
Neovascular age-related macular degeneration (nAMD) has been described as a predominantly inflammatory and proangiogenic retino-choroidal disease. Vitreous humor (VH) is the adjacent and accessible compartment which, due to the vicinity to the retina, might best represent changes of protein-based mediators of nAMD. The aim of this clinical-experime...
Article
Full-text available
Carbohydrates establish the third alphabet of life. As part of cellular glycoconjugates, the glycans generate a multitude of signals in a minimum of space. The presence of distinct glycotopes and the glycome diversity are mapped by sugar receptors (antibodies and lectins). Endogenous (tissue) lectins can read the sugar-encoded information and trans...
Article
Transforming growth factor-β (TGF-β) signaling plays a key role in regulating normal cell growth and differentiation, and mutations affecting members of this pathway contribute to cancer development and metastasis. In DNA mismatch repair (MMR)-deficient colorectal cancers that exhibit the microsatellite instability (MSI) phenotype, biallelic frames...
Article
Objectives: Surgical interventions can cause systemic postoperative inflammation, which in turn can induce neuroinflammation. A close link between immune reaction and cholinergic metabolism has been postulated. Pharmacological enhancement of cholinergic activity by administering physostigmine is known to induce protective effects. It is not known,...
Article
Full-text available
Targeting tumor glycolysis would hit the main energy source of cancer. We show that natural killer (NK) cells pursue this strategy by employing high mobility group box 1 (HMGB1) protein—a well-known proinflammatory cytokine—to specifically target glycolysis in cancer cells. This opens up new perspectives for cancer immunotherapy. © 2016, © 2016 The...
Article
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The high-mobility group box 1 (HMGB1) protein has a central role in immunological antitumour defense. Here we show that natural killer cell-derived HMGB1 directly eliminates cancer cells by triggering metabolic cell death. HMGB1 allosterically inhibits the tetrameric pyruvate kinase isoform M2, thus blocking glucose-driven aerobic respiration. This...
Data
Supplementary Figures 1-4 and Supplementary References.
Article
Galectin-3 is an adhesion/growth-regulatory protein with a modular design comprising an N-terminal tail (NT, residues 1-111) and the conserved carbohydrate recognition domain (CRD, residues 112-250). The chimera-type galectin interacts with both glycan and peptide motifs. Complete 13C/15N-assignment of the human protein makes NMR-based analysis of...
Article
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Inhibitors of the mTOR pathway, such as everolimus, are promising compounds to treat patients with renal cell carcinomas (RCCs). However, the precise mechanisms of action are far from clear, and biomarkers predicting the response to mTOR inhibitors are still missing. Here, we provide evidence that in RCCs the rpS6 protein is the major mediator of a...
Article
Full-text available
To determine intraocular pharmacokinetics of aflibercept and VEGF-A in patients with neovascular age-related macular degeneration (nAMD) during a treatment period of 6 months. Seven nonvitrectomized patients diagnosed with macular edema secondary to nAMD undergoing intravitreal injections (IVI) of aflibercept. Patients were treatment naïve at least...
Article
Aim/Background: Galectins constitute a family of ß-galactoside binding proteins some of them known to be involved in colorectal tumorigenesis. Our previous work suggests that sodium butyrate can induce galectin-12 expression in CRC cell lines. How this might be exerted is largely unexplored. In the present study we examined the potential epigenetic...
Article
About 40% of clear-cell renal cell carcinomas (ccRCC) harbor mutations in Polybromo-1 (PBRM1), encoding the BAF180 subunit of a SWI/SNF chromatin remodeling complex. This qualifies PBRM1 as a major cancer gene in ccRCC. The PBRM1 protein alters chromatin structure and its known functions include transcriptional regulation by controlling the accessi...
Article
Protein-linked glycans play key roles in cell differentiation, cell-cell interactions, cell growth, adhesion and immune response. Aberrant glycosylation is a characteristic feature of tumor cells and is involved in tumor growth, escape from apoptosis, metastasis formation, and resistance to therapy. It can serve as cancer biomarker and treatment ta...
Article
Lectins translate information encoded in glycan chains of cellular glycoconjugates into bioeffects. The topological presentation of contact sites for cognate sugar binding is a crucial factor toward this end. To dissect the significance of such phylogenetically conserved properties, the design and engineering of non-natural variants are attractive...
Article
Full-text available
Although inactivating frameshift mutations in the Transforming growth factor beta receptor type 2 (TGFBR2) gene are considered as drivers of microsatellite unstable (MSI) colorectal tumorigenesis, consequential alterations of the downstream target proteome are not resolved completely. Applying a click-it chemistry protein labeling approach combined...
Article
The profile of cell surface molecules, the biochemical platform for cellular communication, can be likened to a molecular fingerprint. Historically, raising monoclonal antibodies by immunization with cells has been instrumental in obtaining tools suited for phenotyping and functional analysis. Initially for leukocyte antigens, the resulting cluster...
Article
Full-text available
High glucose consumption due to Warburg effect is one of the metabolic hallmarks of cancer. Consequently, glucose antimetabolites, such as 2-deoxy-glucose (2DG), can induce substantial growth inhibition of cancer cells. However, the inhibition of metabolic pathways is not the sole effect of 2DG on cancer cells. As mannose-mimetic molecule, 2DG is b...