Cristin-prosjekt-ID: 520774
Sist endret: 12. januar 2020 22:22

Cristin-prosjekt-ID: 520774
Sist endret: 12. januar 2020 22:22
Prosjekt

Identifying the molecular mechanisms leading to age-related chronic disease onset using an innovative in vivo setup

prosjektleder

Simona Chera
ved Klinisk institutt 2 ved Universitetet i Bergen

prosjekteier / koordinerende forskningsansvarlig enhet

  • Universitetet i Bergen

Finansiering

  • TotalbudsjettNOK 4.000.000
  • Norges forskningsråd
    Prosjektkode: 247577

Klassifisering

Vitenskapsdisipliner

Andre helsefag

Emneord

Utvalgte adulte stamceller • Stamcelleforskning • Diabetes

HRCS-helsekategori

  • Stoffskifte og hormoner

Kategorier

Prosjektkategori

  • Grunnforskning

Tidsramme

Avsluttet
Start: 1. august 2015 Slutt: 31. desember 2019

Beskrivelse Beskrivelse

Tittel

Identifying the molecular mechanisms leading to age-related chronic disease onset using an innovative in vivo setup

Populærvitenskapelig sammendrag

The risk of developing certain disorders increments with age, nearly all life limiting conditions such as cancer, dementia, heart disease or diabetes, being prevalent in the elderly segment of population. This, correlated with the important increase in the lifespan observed in the developed world, has as repercussion an increased number of aged persons living longer, however with multiple age-associated chronic disorders. If this trend is maintained, the economical and social costs of an aging population will be overwhelming. Therefore an approach that will prolong the healthspan (life without chronic illness) by delaying the disease onset is mandatory. Diabetes is characterized by high blood sugar levels resulted from the impaired ability of the body to produce or respond to the hormone insulin. The two common forms of diabetes are exceedingly difficult to study due to their complex aetiology. Consequently, in both cases the major difficulty is distinguishing from the plethora of modulations the ones directly responsible for disease initiation. This project proposes a novel strategy based on the outstanding features presented by a group of monogenic diabetes disorders, termed MODY (Maturity Onset Diabetes of the Young). Induced-pluripotent stem cells derived from different MODY patients will be differentiated into insulin-producing beta-cells. Upon transplantation into humanized diabetic mice, the outcome of their age-related gradual failure will be used to monitor disorder onset. By using this strategy we plan to comprehensively characterize the cellular and molecular basis of monogenic diabetes development as well as search for a common mechanism of maturity-onset disorders initiation. Special emphasis will be given for generation of a short list of novel therapeutic targets for subsequent in vivo testing, which will allow a much more efficient clinical intervention with a greater gain in terms of functionality and healthspan.

Metode

This proposal aims at characterizing the cellular and molecular basis of the gradual failure of insulin-producing beta-cells in diabetes by using a novel in vivo strategy involving transplanted induced pluripotent stem cells (iPSCs) derived from monogenic diabetes patients (MODY patients). We plan to identify a potential general mechanism of disease onset as well as generate a short list of therapeutic targets for subsequent in vivo testing. These aims will be addressed using a three-step strategy (Objectives 1 to 3):
1. Characterization of the cellular mechanisms underlying the natural and gradual decay of iPSC-derived b-cells from MODY patients
2. Identifying of the molecular mechanisms responsible for the gradual decay of from MODY patients
3. Identifying a general molecular mechanisms responsible for MODY onset

prosjektdeltakere

prosjektleder

Simona Chera

  • Tilknyttet:
    Prosjektleder
    ved Klinisk institutt 2 ved Universitetet i Bergen

Zaidon Salim

  • Tilknyttet:
    Prosjektdeltaker
    ved Universitetet i Bergen

Luiza Ghila

  • Tilknyttet:
    Prosjektdeltaker
    ved Universitetet i Bergen

Thomas Aga Legøy

  • Tilknyttet:
    Prosjektdeltaker
    ved Universitetet i Bergen

Helge Ræder

  • Tilknyttet:
    Prosjektdeltaker
    ved Universitetet i Bergen
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Resultater Resultater

In vivo hyperglycemia exposure elicits distinct period-dependent effects on human pancreatic progenitor differentiation, conveyed by oxidative stress.

Legøy, Thomas Aga; Ghila, Luiza; Vethe, Heidrun; Abadpour, Shadab; Mathisen, Andreas Frøslev; Paulo, Joao A.; Scholz, Hanne; Ræder, Helge; Chera, Simona. 2019, Acta Physiologica. HAUKELAND, UIO, OUS, UIB, HMSVitenskapelig artikkel

Encapsulation boosts islet-cell signature in differentiating human induced pluripotent stem cells via integrin signalling.

Vethe, Heidrun; Legøy, Thomas Aga; Abadpour, Shadab; Strand, Berit Løkensgard; Scholz, Hanne; Paulo, Joao A.; Ræder, Helge; Ghila, Luiza; Chera, Simona. 2019, bioRxiv - the preprint server for biology. NTNU, UIO, UIBPopulærvitenskapelig artikkel

Reprogrammed cells display distinct proteomic signaturesAssociated with colony morphology variability.

Bjørlykke, Yngvild; Søviknes, Anne Mette; Hoareau, Laurence; Vethe, Heidrun; Mathisen, Andreas; Chera, Simona; Vaudel, Marc; Ghila, Luiza; Ræder, Helge. 2019, Stem Cells International. HAUKELAND, UIBVitenskapelig artikkel

Probing the missing mature β-cell proteomic landscape in differentiating patient iPSC-derived cells.

Vethne, Heidrun; Bjørlykke, Yngvild; Ghila, Luiza; Paulo, Joao A.; Scholz, Hanne; Gygi, Steven P.; Chera, Simona; Ræder, Helge. 2017, Scientific Reports. HAUKELAND, OUS, HMS, UIBVitenskapelig artikkel
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