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Molecular Medicine

Head
Carlamaria
Zoja
Head of Department
Medicina Molecolare
carlamaria.zoja@marionegri.it
Staff
Daniela
Melacini
Medicina Molecolare
daniela.melacini@marionegri.it

The research of the Department of Molecular Medicine is closely linked to that of the Department of Renal Medicine and aims to understand the mechanisms of damage that lead to the loss of kidney function in chronic kidney diseases, and the development of strategies that avoid the patients needing dialysis or transplantation.

ObJECTIVES

  • Identification of mediators and mechanisms responsible for the relentless decline of renal function in kidney diseases
  • Development of therapeutic interventions (pharmacological, cellular, molecular therapy) to slow or even halt the disease progression to end-stage renal failure
  • Identification of mechanisms of tissue regeneration induced by renoprotective therapies and identification of renal progenitors
  • Generation of new functional nephrons starting from renal embryonic cells
  • Derivation of induced pluripotent stem cells from patients affected by rare diseases and set up of differentiation protocols to generate renal progenitors
  • Correction of genetic mutation in iPS from patients with rare disease by means of CRISPR/Cas9 technique
  • Understanding the mechanisms underlying endothelial cell dysfunction in thrombotic microangiopathies
  • Finding new strategies for modulating the immune response and preventing acute and chronic rejection of kidney allograft as well as exploration of immunological pathways leading to tolerance of the graft
  • Developmentof gene therapy strategies for the cure of genetic rare diseases

METHODOLOGICAL APPROACHES

  • experimental models of kidney diseases mimicking human renal diseases to study vasoactive and inflammatory mediators and to test novel antiproteinuric and renoprotective drugs
  • therapies with stem cells of different origin to cure acute and chronic kidney diseases (bone marrow, umbilical cord, amniotic fluid)
  • glomerular and tubular cell lines
  • induced pluripotent stem cells (iPS)
  • generation of renal organoids by using tissue engeneering approaches
  • in vitro models to assess the interaction of vascular endothelial cells with leukocytes and platelets under controlled flow conditions
  • experimental models of kidney allotransplant to study immunological processes responsible for acute and chronic rejection, the nephrotoxicity of immunosuppressor drugs     as well as to explore pathways responsible for accomodation
  • genetransfer of viral constructs carrying genes encoding immunomodulatory molecules to overcome chronic rejection of allotransplantation avoiding immunosuppression. Use ofviral constructs to correct genetic defects

Results

  • Proved that in acute kidney disease stem cells repair the kidney
  • Obtained a nephron (functional unit of the kidney) in the laboratory, starting with embryonic stem cells
  • Repopulated a diseased kidney, previously deprived of its cells, with stem cells
  • Setup of gene therapy techniques in animals to avoid organ transplant rejection without immunosuppressive drugs
  • Found a way to teach the body to tolerate the transplanted organ without  anti-rejection drugs
  • Developed new therapies for various rare diseases and helped understand how these drugs work

Current projects

NEPHSTROM, Novel Stromal Cell Therapy for Diabetic Kidney Disease


Sponsor: European Commission
Other Departments: Medicina Renale
Area: Trasplant

Dissecting the pathogenetic role of C3a in renal injury of diabetes and therapeutic perspectives
Sponsor: Fondazione Cariplo
Area: Type 2 diabetic nephropathy

 

Mitochondrial dysfunction in diabetic nephropathy: an unanticipated role of Sirtuin 3
Sponsor: Fondazione Cariplo
Other Departments: Fondazione per la Ricerca Biomedica Avanzata Onlus-Istituto Veneto di Medicina Molecolare, Padova
Area: Diabetic nephropathy


Podocyte fetal reprogramming in diabetic nephropathy: the key role of thyroid hormone receptors
Sponsor: European Foundation for the Study of Diabetes

Area: Diabetes

Unravelling the role of PAX2 mutationsin human Focal Segmental Glomerulosclerosis
Sponsor: Fondazione Telethon
Area: Rare diseases

A prospective study to assess safety and efficacy of the use of bone-marrow derived MESenchimal stromal cells as immunomodulatory therapy for children and young adults with severe and difficult to treat frequently relapsing or steroid-dependent idiopathic NEPHrotic syndrome: the MESNEPH study Open label phase 1 trial


Sponsor: Agenzia Italiana del Farmaco AIFA
Area: Nephrotic syndrome

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Scarica il report 2018
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Head
Carlamaria
Zoja
Head of Department
Medicina Molecolare
carlamaria.zoja@marionegri.it
Staff
Daniela
Melacini
Medicina Molecolare
daniela.melacini@marionegri.it
Pagina Italiano