A5037313661- Renal and related cancers
- Cancer Genomics and Diagnostics
- Biosimilars and Bioanalytical Methods
- Biological Research and Disease Studies
- Biomedical Ethics and Regulation
- Enzyme function and inhibition
- Essential Oils and Antimicrobial Activity
- Click Chemistry and Applications
- Synthesis of Organic Compounds
- Immunotherapy and Immune Responses
- Synthesis and Catalytic Reactions
- Hemoglobin structure and function
- Chemical Reactions and Mechanisms
- Curcumin's Biomedical Applications
- Ethnobotanical and Medicinal Plants Studies
- Immune cells in cancer
- Oxidative Organic Chemistry Reactions
- Heme Oxygenase-1 and Carbon Monoxide
- Adenosine and Purinergic Signaling
Sapienza University of Rome
2020-2025
University of Oxford
2024
Ludwig Cancer Research
2024
Tendinopathy is often described as a complex and multifactorial condition which affects tendons. Tendon disorders are marked by reduction in mechanical function, accompanied pain swelling. At the molecular level, tendinopathy leads to oxidative stress-driven inflammation, increased cell death, disruption of extracellular matrix balance, abnormal growth capillaries arteries, degeneration collagen formation. Here, we report an innovative approach modulate stress during based on...
Human carbonic anhydrase (hCA, EC 4.2.1.1) isoforms IX and XII are overexpressed in solid hypoxic tumors, they considered as prognostic tools therapeutic targets for cancer. Based on a molecular simplification of the well-known coumarin scaffold, we developed new series derivatives pyran-2-one core. The compounds endowed with potent selective inhibitory activity against tumor-related hCA XII, low nanomolar range, whereas inactive two cytosolic off-targets I II. exhibiting best inhibition...
Defining the initial events in oncogenesis and cellular responses they entrain, even advance of morphologic abnormality, is a fundamental challenge understanding cancer initiation. As paradigm to address this, we longitudinally studied changes induced by loss tumor suppressor gene von Hippel Lindau (VHL), which ultimately drives clear cell renal carcinoma. Vhl inactivation was directly coupled expression tdTomato reporter within single allele, allowing accurate visualization affected cells...
<p><i>Vhl</i>-null cells exhibit time-dependent proliferation and association with ccRCC-like gene expression. <b>A,</b> Representative dual IHC for tdTomato (brown) Ki67 (purple) counterstained hematoxylin in kidneys of KO mice harvested early after recombination. Scale bar, 25 μm. Magnification, ×40. Black arrow, dual-positive cell; red tdTomato-negative Ki67-positive cell. <b>B,</b> Proportion tdTomato-positive (top) or (bottom) that are positive...
<p>Renal cortex, but not the papilla, is permissive to long-term survival of <i>Vhl</i>-null cells. <b>A,</b> Representative tdTomato IHC counterstained with hematoxylin in different renal anatomical regions Control or KO mice harvested at early late time points. Scale bar, 100 μm. Magnification, ×20. <b>B,</b> Proportion cells that are tdTomato-positive kidney as quantified by kidneys from intervals after recombination. <i>n</i> = 7F,...
<p>Vhl-null cells specifically undergo time-dependent alterations in gene expression</p>
<p>Biallelic Vhl loss entrains early cell-specific transcriptomic changes in renal tubular cells</p>
<p><i>Vhl</i>-null cells specifically undergo time-dependent alterations in gene expression. <b>A,</b> Density plot depicting UMAP distribution of tdTomato-positive from kidneys Control and KO mice harvested at the early or late time points. <b>B,</b> Left, points colored by cluster. Right, proportion each condition belonging to any <b>C,</b> Scatter frequency expression point against log<sub>2</sub>-fold change...
<p>Biallelic <i>Vhl</i> inactivation entrains early cell-specific transcriptomic changes in RTE cells. <b>A,</b> Density plot depicting UMAP distribution of tdTomato-negative and -positive cells from kidneys Control KO mice harvested after recombination. <b>B,</b> Left, recombination colored by clusters. Right, proportion each condition belonging to any cluster. <b>C,</b> Scatter frequency expression (top) or tdTomato-positive (bottom)...
<p><i>Vhl</i>-null cells specifically undergo time-dependent alterations in gene expression. <b>A,</b> Density plot depicting UMAP distribution of tdTomato-positive from kidneys Control and KO mice harvested at the early or late time points. <b>B,</b> Left, points colored by cluster. Right, proportion each condition belonging to any <b>C,</b> Scatter frequency expression point against log<sub>2</sub>-fold change...
<p>A novel reporter model for <i>Vhl</i> inactivation in the mouse kidney. <b>A,</b> Design and recombination of cell marking conditional <i>Vhl<sup>pjr</sup></i> allele. Double single arrows indicate reversible irreversible processes, respectively. <i>Vhl<sup>pjr.fl</sup>, Vhl<sup>pjr.inrec</sup></i>, <i>Vhl<sup>pjr.KO</sup></i> refer to “floxed,” “incompletely recombined,”...
<p>Renal cortex, but not the papilla, is permissive to long-term survival of <i>Vhl</i>-null cells. <b>A,</b> Representative tdTomato IHC counterstained with hematoxylin in different renal anatomical regions Control or KO mice harvested at early late time points. Scale bar, 100 μm. Magnification, ×20. <b>B,</b> Proportion cells that are tdTomato-positive kidney as quantified by kidneys from intervals after recombination. <i>n</i> = 7F,...
<p>scRNA-seq on flow-sorted renal cells. <b>A,</b> UMAP plot of tdTomato-negative (left) or tdTomato-positive cells (right) from kidneys Control mice harvested at the early time point. Cells are colored by inferred cell type. LoH, loop Henle; DCT, distal convoluted tubule; CD, collecting duct; PC, principal cell; IC, intercalated; PEC, parietal epithelial VSMC, vascular smooth muscle NK, natural killer cell. <b>B,</b> Proportion sequenced to be each type in...
<p>Single-cell RNA sequencing on flow-sorted renal cells</p>
<p>A novel reporter model for <i>Vhl</i> inactivation in the mouse kidney. <b>A,</b> Design and recombination of cell marking conditional <i>Vhl<sup>pjr</sup></i> allele. Double single arrows indicate reversible irreversible processes, respectively. <i>Vhl<sup>pjr.fl</sup>, Vhl<sup>pjr.inrec</sup></i>, <i>Vhl<sup>pjr.KO</sup></i> refer to “floxed,” “incompletely recombined,”...
<p>Biallelic <i>Vhl</i> inactivation entrains early cell-specific transcriptomic changes in RTE cells. <b>A,</b> Density plot depicting UMAP distribution of tdTomato-negative and -positive cells from kidneys Control KO mice harvested after recombination. <b>B,</b> Left, recombination colored by clusters. Right, proportion each condition belonging to any cluster. <b>C,</b> Scatter frequency expression (top) or tdTomato-positive (bottom)...
<p>Vhl-null cells specifically undergo time-dependent alterations in gene expression</p>
<p><i>Vhl</i>-null cells exhibit time-dependent proliferation and association with ccRCC-like gene expression. <b>A,</b> Representative dual IHC for tdTomato (brown) Ki67 (purple) counterstained hematoxylin in kidneys of KO mice harvested early after recombination. Scale bar, 25 μm. Magnification, ×40. Black arrow, dual-positive cell; red tdTomato-negative Ki67-positive cell. <b>B,</b> Proportion tdTomato-positive (top) or (bottom) that are positive...
<p>Biallelic Vhl loss entrains early cell-specific transcriptomic changes in renal tubular cells</p>
<p>Single-cell RNA sequencing on flow-sorted renal cells</p>
<p>scRNA-seq on flow-sorted renal cells. <b>A,</b> UMAP plot of tdTomato-negative (left) or tdTomato-positive cells (right) from kidneys Control mice harvested at the early time point. Cells are colored by inferred cell type. LoH, loop Henle; DCT, distal convoluted tubule; CD, collecting duct; PC, principal cell; IC, intercalated; PEC, parietal epithelial VSMC, vascular smooth muscle NK, natural killer cell. <b>B,</b> Proportion sequenced to be each type in...
<div>Abstract<p>Defining the initial events in oncogenesis and cellular responses they entrain, even advance of morphologic abnormality, is a fundamental challenge understanding cancer initiation. As paradigm to address this, we longitudinally studied changes induced by loss tumor suppressor gene von Hippel Lindau (<i>VHL</i>), which ultimately drives clear cell renal carcinoma. <i>Vhl</i> inactivation was directly coupled expression tdTomato reporter...