Leptin Receptor Fibroblasts Are Preferential Contributors to Cardiac Fibrosis Veronica Larcher, Ariane Fischer, Lunfeng Zhang, Omar Almolla, Mattia Chiesa, Francesca Andriani, Chiara Wernet, Simone Serio, Lukas Tombor, Sofia Peruzzo, Debanjan Mukherjee, Rossana Bussani, Serena Zacchigna, Ralf H. Adams, Stefanie Dimmeler, Sylvia M. Evans, Paola Cattaneo, Nuno Guimarães-Camboa Circulation Research, 2026 BACKGROUND: Cardiac fibrosis, a hallmark of heart failure and an unmet clinical need, arises from pathological activation of preexisting cardiac fibroblasts (CFs), but the contribution of CF heterogeneity to this process remains unclear. METHODS: Murine models were used to lineage trace or deplete a specific sub-population of CFs at baseline and after myocardial infarction. Transcriptional and epigenetic differences between fibroblast subsets were assessed using next-generation sequencing. Conservation in humans was evaluated through single-cell RNA-seq data sets and histological examination. RESULTS: In mice, fibroblasts were the sole cardiac cell type expressing the signaling-capable isoform of the LepR (leptin receptor). LepR+ CFs emerged neonatally, occupied a defined niche in the coronary adventitia, exhibited enhanced hedgehog signaling, and responded to leptin. After myocardial infarction, LepR-Cre+ CFs proliferated more than interstitial CFs, became a predominant fibroblast lineage in the scar, and their genetic ablation reduced fibrosis while improving function. LepR+ CFs were also detected in the human heart, where they were embedded in an adipocyte-rich niche. CONCLUSIONS: These findings identify adventitial fibroblasts as key drivers of pathological remodeling and demonstrate that fibroblasts, rather than cardiomyocytes, are the principal responders to leptin in the heart, redefining how this major endocrine pathway influences cardiac remodeling and disease.
RNA binding of GAPDH controls transcript stability and protein translation in acute myeloid leukemia Sama Shamloo, Jeffrey L. Schloßhauer, Shashank Tiwari, Kim Denise Fischer, Omar Almolla, Yohana Ghebrechristos, Lisa Kratzenberg, Aathma Merin Bejoy, Ioannis Aifantis, Francesco Boccalatte, Eric Wang, Jochen Imig RNA Biology, 2025 Dysregulation of RNA binding proteins (RBPs) is a hallmark in cancerous cells. In acute myeloid leukaemia (AML) RBPs are key regulators of tumour proliferation. While classical RBPs have defined RNA binding domains, RNA recognition and function in AML by non-canonical RBPs (ncRBPs) remain unclear. Given the inherent complexity of targeting AML broadly, our goal was to uncover potential ncRBP candidates critical for AML survival using a CRISPR/Cas-based screening. We identified the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as a pro-proliferative factor in AML cells. Based on cross-linking and immunoprecipitation (CLIP), we are defining the global targetome, detecting novel RNA targets mainly located within 5'UTRs, including GAPDH, RPL13a, and PKM. The knockdown of GAPDH unveiled genetic pathways related to ribosome biogenesis, translation initiation, and regulation. Moreover, we demonstrated a stabilizing effect through GAPDH binding to target transcripts including its own mRNA. The present findings provide new insights on the RNA functions and characteristics of GAPDH in AML.
Microbiota profiling in esophageal diseases: Novel insights into molecular staining and clinical outcomes Alberto Barchi, Luca Massimino, Francesco Vito Mandarino, Edoardo Vespa, Emanuele Sinagra, Omar Almolla, Sandro Passaretti, Ernesto Fasulo, Tommaso Lorenzo Parigi, Stefania Cagliani, Salvatore Spanò, Federica Ungaro, Silvio Danese Computational and Structural Biotechnology Journal, 2024 Gut microbiota is recognized nowadays as one of the key players in the development of several gastro-intestinal diseases. The first studies focused mainly on healthy subjects with staining of main bacterial species via culture-based techniques. Subsequently, lots of studies tried to focus on principal esophageal disease enlarged the knowledge on esophageal microbial environment and its role in pathogenesis.Gastro Esophageal Reflux Disease (GERD), the most widespread esophageal condition, seems related to a certain degree of mucosal inflammation, via interleukin (IL) 8 potentially enhanced by bacterial components, lipopolysaccharide (LPS) above all. Gram- bacteria, producing LPS), such as Campylobacter genus, have been found associated with GERD.Barrett esophagus (BE) seems characterized by a Gram- and microaerophils-shaped microbiota.Esophageal cancer (EC) development leads to an overturn in the esophageal environment with the shift from an oral-like microbiome to a prevalently low-abundant and low-diverse Gram--shaped microbiome.Although underinvestigated, also changes in the esophageal microbiome are associated with rare chronic inflammatory or neuropathic disease pathogenesis.The paucity of knowledge about the microbiota-driven mechanisms in esophageal disease pathogenesis is mainly due to the scarce sensitivity of sequencing technology and culture methods applied so far to study commensals in the esophagus.However, the recent advances in molecular techniques, especially with the advent of non-culture-based genomic sequencing tools and the implementation of multi-omics approaches, have revolutionized the microbiome field, with promises of implementing the current knowledge, discovering more mechanisms underneath, and giving insights into the development of novel therapies aimed to re-establish the microbial equilibrium for ameliorating esophageal diseases.
Report on the sequencing of the sour cherry (Prunus cerasus L.) 'Schattenmorelle' genome T. Wöhner, O.F. Emeriewen, A.H.J. Wittenberg, K. Nijbroek, R.P. Wang, E.-J. Blom, J. Keilwagen, T. Berner, K.J. Hoff, L. Gabriel, H. Thierfeldt, O. Almolla, L. Barchi, M. Schuster, J. Lempe, A. Peil, H. Flachowsky Acta Horticulturae, 2024 Precise whole genome sequencing and accurate annotation provides a wealth of information on crops, for example the location of genes for important traits, or the structure of the genome itself. More than one whole genome sequence for fruit trees such as peach, apple, pear and sweet cherry are available to accelerate the breeding process, select desirable traits, and breed new cultivars. to date, there is no published genome of sour cherry (Prunus cerasus L., 2n=4x=32). It is assumed that sour cherry consists of complex segmental allotetraploid genome that developed from an ancient hybridization event between unreduced pollen of diploid P. avium L. (2n=2x=16) and the gametes of tetraploid P. fruticosa (2n=4x=32). Structural changes within the genome sequence that evolved during the evolution of this species, especially within its subgenomes, could result in the occurrence of auto- and allopolyploid genomic segments. In this study, we report whole genome and transcriptome sequencing of sour cherry cultivar Schattenmorelle with subsequent assembly to a pseudo-chromosome-level representing a model sequence with gene annotation (Wöhner et al., 2023). Our study furthermore investigated the occurrence of structural differences compared to ancestor-representing genome sequences obtained from P. avium ‘Tieton’ and P. fruticosa ecotype Hármashatárhegy.
The structure of the tetraploid sour cherry ‘Schattenmorelle’ (Prunus cerasus L.) genome reveals insights into its segmental allopolyploid nature Thomas W. Wöhner, Ofere F. Emeriewen, Alexander H. J. Wittenberg, Koen Nijbroek, Rui Peng Wang, Evert-Jan Blom, Harrie Schneiders, Jens Keilwagen, Thomas Berner, Katharina J. Hoff, Lars Gabriel, Hannah Thierfeldt, Omar Almolla, Lorenzo Barchi, Mirko Schuster, Janne Lempe, Andreas Peil, Henryk Flachowsky Frontiers in Plant Science, 2023 Sour cherry (Prunus cerasus L.) is an important allotetraploid cherry species that evolved in the Caspian Sea and Black Sea regions from a hybridization of the tetraploid ground cherry (Prunus fruticosa Pall.) and an unreduced pollen of the diploid sweet cherry (P. avium L.) ancestor. Details of when and where the evolution of this species occurred are unclear, as well as the effect of hybridization on the genome structure. To gain insight, the genome of the sour cherry cultivar ‘Schattenmorelle’ was sequenced using Illumina NovaSeqTM and Oxford Nanopore long-read technologies, resulting in a ~629-Mbp pseudomolecule reference genome. The genome could be separated into two subgenomes, with subgenome PceS_a originating from P. avium and subgenome PceS_f originating from P. fruticosa. The genome also showed size reduction compared to ancestral species and traces of homoeologous sequence exchanges throughout. Comparative analysis confirmed that the genome of sour cherry is segmental allotetraploid and evolved very recently in the past.
RECENT SCHOLAR PUBLICATIONS
Microbiota profiling in esophageal diseases: Novel insights into molecular staining and clinical outcomes A Barchi, L Massimino, FV Mandarino, E Vespa, E Sinagra, O Almolla, ... Computational and structural biotechnology journal 23, 626-637 , 2024 2024 Citations: 30
The structure of the tetraploid sour cherry ‘Schattenmorelle’ ( Prunus cerasus L.) genome reveals insights into its segmental allopolyploid nature TW Wöhner, OF Emeriewen, AHJ Wittenberg, K Nijbroek, RP Wang, ... Frontiers in Plant Science 14, 1284478 , 2023 2023 Citations: 11
Report on the sequencing of the sour cherry (Prunus cerasus L.) Schattenmorelle genome T Wöhner, OF Emeriewen, AHJ Wittenberg, K Nijbroek, RP Wang, ... XVI EUCARPIA Symposium on Fruit Breeding and Genetics 1412, 443-446 , 2023 2023
Data set: The structure of the tetraploid sour cherry'Schattenmorelle'(Prunus cerasus L.) genome reveals insights into its segmental allopolyploid nature T Wöhner, OF Emeriewen, AHJ Wittenberg, K Nijbroek, RP Wang, ... 2023 Citations: 1
Salt-tolerant rootstock increases yield of pepper under salinity through maintenance of photosynthetic performance and sinks strength C Penella, M Landi, L Guidi, SG Nebauer, E Pellegrini, A San Bautista, ... Journal of plant physiology 193, 1-11 , 2016 2016 Citations: 149
MOST CITED SCHOLAR PUBLICATIONS
Salt-tolerant rootstock increases yield of pepper under salinity through maintenance of photosynthetic performance and sinks strength C Penella, M Landi, L Guidi, SG Nebauer, E Pellegrini, A San Bautista, ... Journal of plant physiology 193, 1-11 , 2016 2016 Citations: 149
Microbiota profiling in esophageal diseases: Novel insights into molecular staining and clinical outcomes A Barchi, L Massimino, FV Mandarino, E Vespa, E Sinagra, O Almolla, ... Computational and structural biotechnology journal 23, 626-637 , 2024 2024 Citations: 30
The structure of the tetraploid sour cherry ‘Schattenmorelle’ ( Prunus cerasus L.) genome reveals insights into its segmental allopolyploid nature TW Wöhner, OF Emeriewen, AHJ Wittenberg, K Nijbroek, RP Wang, ... Frontiers in Plant Science 14, 1284478 , 2023 2023 Citations: 11
Data set: The structure of the tetraploid sour cherry'Schattenmorelle'(Prunus cerasus L.) genome reveals insights into its segmental allopolyploid nature T Wöhner, OF Emeriewen, AHJ Wittenberg, K Nijbroek, RP Wang, ... 2023 Citations: 1
Report on the sequencing of the sour cherry (Prunus cerasus L.) Schattenmorelle genome T Wöhner, OF Emeriewen, AHJ Wittenberg, K Nijbroek, RP Wang, ... XVI EUCARPIA Symposium on Fruit Breeding and Genetics 1412, 443-446 , 2023 2023