Rüdiger Rudolf

Rüdiger Rudolf
Hochschule Mannheim · Institute of Molecular and Cell Biology (MZ)

Professor

About

131
Publications
68,581
Reads
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9,337
Citations
Introduction
We are working on technologies to design, apply, and analyze three-dimensional models for compound testing and mechanistic understanding of disease. In cooperative projects with health industries and academic partners we have worked on models for skeletal muscle and neurobiology, taste physiology, skin, and cancer. We use iPSC and cell lines to form spheroid, chip-based cultures and organoids, analyzed by biochemistry, immunofluorescence, tissue clearing, 3D-microscopy, deep learning approaches.
Additional affiliations
March 2020 - present
Hochschule Mannheim
Position
  • Professor
May 2014 - present
Universität Heidelberg
Position
  • Investigator
September 2005 - March 2012
Karlsruhe Institute of Technology
Position
  • Group Leader

Publications

Publications (131)
Article
Full-text available
3D cell culture models are important tools for the development and testing of new therapeutics. In combination with immunoassays and 3D confocal microscopy, crucial information like morphological or metabolic changes can be examined during drug testing. However, a common limitation of immunostainings is the number of dyes that can be imaged simulta...
Article
Full-text available
Cancer therapy is an emergent application for mRNA therapeutics. While in tumor immunotherapy, mRNA encoding for tumor-associated antigens is delivered to antigen-presenting cells in spleen and lymph nodes, other therapeutic options benefit from immediate delivery of mRNA nanomedicines directly to the tumor. However, tumor targeting of mRNA therape...
Article
Full-text available
Motoneurons, skeletal muscle fibers, and Schwann cells form synapses, termed neuromuscular junctions (NMJs). These control voluntary body movement and are affected in numerous neuromuscular diseases. Therefore, a variety of NMJ in vitro models have been explored to enable mechanistic and pharmacological studies. So far, selective integration of Sch...
Article
Full-text available
Sweetness is the preferred taste of humans and many animals, likely because sugars are a primary source of energy. In many mammals, sweet compounds are sensed in the tongue by the gustatory organ, the taste buds. Here, a group of taste bud cells expresses a canonical sweet taste receptor, whose activation induces Ca ²⁺ rise, cell depolarization and...
Article
Full-text available
Bone sialoprotein (BSP) has become a target in breast cancer research as it is associated with tumor progression and metastasis. The mechanisms underlying the regulation of BSP expression have been largely elusive. Given that BSP is involved in the homing of cancer cells in bone metastatic niches, we addressed regulatory effects of proteolytic clea...
Chapter
Most currently available three-dimensional melanoma models have either focused on simplicity or were optimized for physiological relevance. Accordingly, these paradigms have been either composed of malignant cells only or they were sophisticated human skin equivalents featuring multiple cell types and skin-like organization. Here, an intermediate s...
Article
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Recent studies have demonstrated that neuromuscular junctions are co-innervated by sympathetic neurons. This co-innervation has been shown to be crucial for neuromuscular junction morphology and functional maintenance. To improve our understanding of how sympathetic innervation affects nerve–muscle synapse homeostasis, we here used in vivo imaging,...
Article
Full-text available
In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monit...
Preprint
Full-text available
In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monit...
Preprint
Full-text available
the PDF can be download freely on pubmed. https://pubmed.ncbi.nlm.nih.gov/33634751/
Cover Page
Full-text available
In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monit...
Article
Full-text available
Sweet substances are detected by taste-bud cells upon binding to the sweet-taste receptor, a T1R2/T1R3 heterodimeric G protein-coupled receptor. In addition, experiments with mouse models lacking the sweet-taste receptor or its downstream signaling components led to the proposal of a parallel “alternative pathway” that may serve as metabolic sensor...
Article
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The analysis of microscopic images from cell cultures plays an important role in the development of drugs. The segmentation of such images is a basic step to extract the viable information on which further evaluation steps are build. Classical image processing pipelines often fail under heterogeneous conditions. In the recent years deep neuronal ne...
Article
Full-text available
Most tumors consume large amounts of glucose. Concepts to explain the mechanisms that mediate the achievement of this metabolic need have proposed a switch of the tumor mass to aerobic glycolysis. Depending on whether primarily tumor or stroma cells undergo such a commutation, the terms ‘Warburg effect’ or ‘reverse Warburg effect’ were coined to de...
Article
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Amongst other approaches, adipose-derived stromal cells (ASCs) have recently been tested with respect to their regenerative capacity for treatment of neuromuscular disorders. While beneficial effects of ASCs on muscle recovery were observed previously, their impact on regeneration of neuromuscular junctions (NMJs) is unclear. Here, we used a murine...
Article
Full-text available
The five basic taste modalities, sweet, bitter, umami, salty and sour induce changes of Ca2+ levels, pH and/or membrane potential in taste cells of the tongue and/or in neurons that convey and decode gustatory signals to the brain. Optical biosensors, which can be either synthetic dyes or genetically encoded proteins whose fluorescence spectra depe...
Article
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Three-dimensional cell cultures, such as spheroids and organoids, serve as increasingly important models in fundamental and applied research and start to be used for drug screening purposes. Optical tissue clearing procedures are employed to enhance visualization of fluorescence-stained organs, tissues, and three-dimensional cell cultures. To get a...
Article
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The protein kinase Csnk2/CK2 is important for cell proliferation, differentiation, and survival. Previously, we showed that CK2 binds distinctive proteins at neuromuscular junctions (NMJs) of mice and phosphorylates some of them. CK2 likely stabilizes clustered nicotinic acetylcholine receptors (AChRs). In the absence of the β-subunit of CK2 in ske...
Article
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Objective Although it is well established that a-calcitonin gene-related peptide (CGRP) stabilizes muscle-type cholinergic receptors nicotinic subunits (AChR), the underlying mechanism by which this neuropeptide regulates muscle protein metabolism and neuromuscular junction (NMJ) morphology is unclear. Methods To elucidate the mechanisms how CGRP...
Article
Full-text available
At vertebrate motor endplates, the conversion of nerve impulses into muscle contraction is initiated by binding of acetylcholine to its nicotinic receptor (nAChR) at the postsynapse. Efficiency and safety of this process are dependent on proper localization, density, and molecular composition of the receptors. To warrant this, intricate machineries...
Article
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Loss of innervation of skeletal muscle is a determinant event in several muscle diseases. Although several effectors have been identified, the pathways controlling the integrated muscle response to denervation remain largely unknown. Here, we demonstrate that PKB/Akt and mTORC1 play important roles in regulating muscle homeostasis and maintaining n...
Article
Full-text available
Background Different 3D-cell culture approaches with varying degrees of complexity have been developed to serve as melanoma models for drug testing or mechanistic studies. While these 3D-culture initiatives are already often superior to classical 2D approaches, they are either composed of only melanoma cells or they are so complex that the behavior...
Article
Full-text available
By mediating voluntary muscle movement, vertebrate neuromuscular junctions (NMJ) play an extraordinarily important role in physiology. While the significance of the nerve-muscle connectivity was already conceived almost 2000 years back, the precise cell and molecular biology of the NMJ have been revealed in a series of fascinating research activiti...
Article
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Neuromuscular junctions (NMJs) mediate skeletal muscle contractions and play an important role in several neuromuscular disorders when their morphology and function are compromised. However, due to their small size and sparse distribution throughout the comparatively large, inherently opaque muscle tissue the analysis of NMJ morphology has been lim...
Article
Full-text available
Normally, bone sialoprotein (BSP) is an important contributor to bone micro-calcification. However, it is also highly expressed in bone-metastatic malignancies, including prostate, lung, and breast cancer. In these disorders, BSP correlates with poor prognosis. Its expression in triple-negative breast cancer cells is enhanced by the transcription f...
Article
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Understanding vascular structures and dysfunction is a fundamental challenge. This task has been approached by using traditional methodologies such as microscopic computed tomography and magnetic resonance imaging. Both techniques are not only expensive but also time-consuming. Here, we present a new method for visualizing vascular structures in di...
Chapter
Ca²⁺ regulates many functions of skeletal muscle, including excitation-contraction coupling, energy homeostasis, and fiber-type-specific gene expression. However, microscopic observation of Ca²⁺ signalling in live skeletal muscle tissue has been hampered, in particular, by the combination of the high speed of Ca²⁺ transients and the contractile pro...
Article
Background: Marinesco-Sjögren Syndrome (MSS) is a rare neuromuscular condition caused by recessive mutations in the SIL1 gene resulting in the absence of functional SIL1 protein, a co-chaperone for the major ER chaperone, BiP. As BiP is decisive for proper protein processing, loss of SIL1 results in the accumulation of misshaped proteins. This acc...
Article
Full-text available
Vertebrate neuromuscular junctions (NMJs) have been conceived as tripartite synapses composed of motor neuron, Schwann cell, and muscle fiber. Recent work has shown the presence of sympathetic neurons in the immediate vicinity of NMJs and experimental and clinical findings suggest that this plays an eminent role in adult NMJ biology. The present st...
Article
Full-text available
Glutamine-fructose-6-phosphate transaminase 1 (GFPT1) is the rate-limiting enzyme in the hexosamine biosynthetic pathway which yields precursors required for protein and lipid glycosylation. Mutations in GFPT1 and other genes downstream of this pathway cause congenital myasthenic syndrome (CMS) characterised by fatigable muscle weakness due to impa...
Data
Figure S1. No association between the scores achieved in the weights test and body weight. Figure S2. AChR clusters in fetal diaphragms of WT and Gnpat KO mice. Figure S3. AChR clusters in skeletal muscles of adult WT and Gnpat KO mice. Figure S4. In vivo ligand binding for fluorescence‐based evaluation of AChR stability in WT and Gnpat KO mice...
Article
In yeast, Tom22 the central component of the TOMM (translocase of outer mitochondrial membrane) receptor complex is responsible for the recognition and translocation of synthesized mitochondrial precursor proteins, and its protein kinase CK2-dependent phosphorylation is mandatory for TOMM complex biogenesis and proper mitochondrial protein import....
Article
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INTRODUCTION: In recent years, many different methods were introduced for generation of 3D cell culture. However, many currently available three-dimensional techniques are not suitable for certain cell lines and sometimes showed a lack of reproducibility. Therefore, specific protocols for cell lines are needed. In this work, we demonstrate differen...
Article
Aim: Neuromuscular junction (NMJ) represents the morphofunctional interface between muscle and nerve. Several chronic pathologies such as aging and neurodegenerative diseases, including muscular dystrophy and amyotrophic lateral sclerosis, display altered NMJ and functional denervation. However, the triggers and the molecular mechanisms underlying...
Article
Full-text available
Inherited deficiency in ether lipids, a subgroup of phospholipids whose biosynthesis needs peroxisomes, causes the fatal human disorder rhizomelic chondrodysplasia punctata. The exact roles of ether lipids in the mammalian organism and, therefore, the molecular mechanisms underlying the disease are still largely enigmatic. Here, we used glyceroneph...
Article
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Vertebrate skeletal muscle contraction is mediated by nicotinic acetylcholine receptors (CHRN). Endocytosis and recycling of CHRN regulate their proper abundance at nerve-muscle synapses, i.e. neuromuscular junctions. Recent work showed that RAB5 is essential for CHRN endocytosis. Here, using in vivo-imaging of endocytosed CHRN and RAB-GFP fusion p...
Article
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Endocytosed nicotinic acetylcholine receptors (CHRN) are degraded via macroautophagy/autophagy during atrophic conditions and are accompanied by the autophagic regulator protein SH3GLB1. The present study addressed the functional role of SH3GLB1 on CHRN trafficking and its implementation. We found an augmented ratio of total SH3GLB1 to threonine-14...
Article
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Missense single-nucleotide polymorphisms (mSNPs) in titin are emerging as a main causative factor of heart failure. However, distinguishing between benign and disease-causing mSNPs is a substantial challenge. Here, we research the question of whether a single mSNP in a generic domain of titin can affect heart function as a whole and, if so, how. Fo...
Article
In 1718, French surgeon Jean-Louis Petit refined the methods to prevent haemorrhage from severely injured limbs by a combined screw and pad attached to a bandage (Kirkup, 2007). He named this device tourniquet (from French tourner = to turn), because the screw allowed fine adjustment of the application without moving the bandage component. Since th...