- Renal and related cancers
- MicroRNA in disease regulation
- Renal Diseases and Glomerulopathies
- Genetic and Kidney Cyst Diseases
- CRISPR and Genetic Engineering
- Renal cell carcinoma treatment
- Pluripotent Stem Cells Research
- Metabolism and Genetic Disorders
- Cancer-related molecular mechanisms research
- Platelet Disorders and Treatments
- Biochemical Acid Research Studies
- Circular RNAs in diseases
- Complement system in diseases
- Virus-based gene therapy research
- Adipose Tissue and Metabolism
- Protein Kinase Regulation and GTPase Signaling
- Phagocytosis and Immune Regulation
- Computational Drug Discovery Methods
- Xenotransplantation and immune response
- Immunotherapy and Immune Responses
- CAR-T cell therapy research
- Sirtuins and Resveratrol in Medicine
- Mitochondrial Function and Pathology
- Reproductive Biology and Fertility
- Immune cells in cancer
Mario Negri Institute for Pharmacological Research
2009-2025
Istituti di Ricovero e Cura a Carattere Scientifico
2017-2023
University of Milan
2019
University of Pavia
2005-2008
Aims: Sirtuins, a family of NAD+-dependent deacetylases, are recognized as nondispensable regulators aging processes. Sirtuin 3 (SIRT3) is the main mitochondrial deacetylase that maintains bioenergetics, an essential prerequisite for healthy aging. In this study, using Sirt3 knockout (Sirt3-/-) mice, we sought to establish whether deficiency affected life span, endpoint has never been tested formally in mammals, and uncover mechanisms involved organ damage associated with Results:Sirt3-/-...
The contribution of microRNA (miRNA) to the pathogenesis renal fibrosis is not well understood. Here, we investigated whether miRNA modulates fibrotic process in Munich Wistar Fromter (MWF) rats, which develop spontaneous progressive nephropathy. We analyzed expression profile microdissected glomeruli and found that miR-324-3p was most upregulated. In situ hybridization localized glomerular podocytes, parietal cells Bowman's capsule, abundantly, cortical tubules. A predicted target prolyl...
Renal fibrosis is a common complication of diabetic nephropathy and major cause end-stage renal disease. Despite the suggested link between microRNA (miRNA) dysregulation in nephropathy, identification specific miRNAs involved still incomplete. The aim this study was to investigate miRNA profiles kidney identify potential downstream targets implicated fibrosis. expression profiling investigated kidneys 8-month-old Zucker fatty (ZDF) rats during overt nephropathy. Localisation most...
We examined the immune response in subjects previously infected with SARS-CoV2 and infection-naïve 9 months after primary 2-dose COVID-19 mRNA vaccination 3 booster dose a longitudinal cohort of healthcare workers. Nine vaccination, exhibited higher residual antibody levels, significant neutralizing activity against distinct variants compared to subjects. The humoral was associated levels receptor binding domain (RBD)-specific IgG+ IgA+ memory B cells. increased neither activity, nor T cell...
Autosomal dominant polycystic kidney disease (ADPKD) is the most common renal genetic disease, with patients carrying mutations in PKD1. The main feature formation of bilateral cysts, leading to end stage failure a significant proportion those affected. Despite recent advances made understanding ADPKD, there are currently no effective curative therapies. emergence human induced pluripotent stem cell (hiPSC)-derived models has led renewed hope that more physiological systems will allow for...
Abstract Members of the TLR/IL-1R superfamily mediate ischemia/reperfusion injury and initiate immune response in transplanted organs. In this study, we tested hypothesis that Toll-IL-1R8 (TIR8), a negative regulator highly expressed kidney, modulates cell activation underlying kidney rejection. mouse model fully mismatched allotransplantation which graft is spontaneously accepted, intragraft Tir8 expression was enhanced compared with naive kidneys. Targeted deletion exerted powerful...
Abstract Abnormal kidney development leads to lower nephron number, predisposing renal diseases in adulthood. In embryonic kidneys, endowment is dictated by the availability of progenitors, whose self-renewal and differentiation require a relatively repressed chromatin state. More recently, NAD + -dependent deacetylase sirtuins (SIRTs) have emerged as possible regulators that link epigenetic processes metabolism. Here, we discovered novel role for deacylase SIRT3 development. kidney, was...
Induced pluripotent stem cells (iPSC) have huge potential as cell therapy for various diseases, given their unlimited self-renewal and capability to differentiate into a wide range of types. Although autologous iPSCs represents the ideal source patient-tailored regenerative medicine, high costs extensive time-consuming production process impracticability treating acute conditions hinder use broad applications. An allogeneic iPSC-based strategy may overcome these issues, but it carries risk...
Focal segmental glomerulosclerosis (FSGS) is defined by focal (involving few glomeruli) and sclerosis of the glomerular tuft that manifests with nephrotic syndrome. Mutations in genes involved maintenance structure function podocytes have been found a minority these patients. A family adult-onset autosomal dominant FSGS was recently to carry new germline missense heterozygous mutation (p.G189R) octapeptide domain transcription factor PAX2. Here, we efficiently corrected this point...
No effective treatments are available for familial steroid-resistant Focal Segmental Glomerulosclerosis (FSGS), characterized by proteinuria due to ultrastructural abnormalities in glomerular podocytes. Here, we studied a private PAX2 mutation identified patient who developed FSGS adulthood. By generating adult podocytes using patient-specific induced pluripotent stem cells (iPSC), an vitro model dissect the role of this onset FSGS. Despite mutation, iPSC properly differentiated into that...
Autosomal dominant polycystic kidney disease (ADPKD) is the most prevalent inherited renal disease, characterized by multiple cysts that can lead to failure resulting in end-stage disease. ADPKD mainly caused mutations either PKD1 and PKD2 genes, encoding for polycystin-1 polycystin-2, respectively. In order clarify mechanisms, here we describe generation of two isogenic induced pluripotent stem cell (iPSC) lines which gene was deleted using CRISPR/Cas9 technology. The PKD2-/- iPSCs...
Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary disease, characterised by development of multiple fluid-filled cysts in kidneys and other organs. PKD1 PKD2 are two major causative genes encoding for polycystin-1 polycystin-2, respectively. Here, we report generation isogenic induced pluripotent stem cell (iPSC) lines with either heterozygous or compound mutations gene using CRISPR-Cas9 technology. The
Human induced pluripotent stem cells (iPSCs) have great promise in regenerative medicine. However, several limitations, including immune-incompatibility, raised concerns regarding their clinical application. Recent studies shown that human iPSCs and derivatives lose immunogenicity when major histocompatibility complex (MHC) class I II genes are inactivated CD47 is over-expressed. In this study, we used CRISPR-Cas9 technology to generate an isogenic iPSC line with a homozygous frameshift...