The second project of the lab is funded by the Research Council of Norway, as a Young Talent Research Project. This 4-year project is aiming at characterizing the cellular and molecular basis of the gradual failure of insulin-producing β-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.
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.
The Stem Cell Research program of the Research Council of Norway has as a primary objective to develop and enhance expertise within basic and clinical research on stem cells, with the aim of finding treatment for seriously and chronically ill patients. The program will employ research and innovation activities with the long term aim of providing patients in Norway with a future range of stem cell-based treatments equivalent to those found abroad. Priority will be given to increasing translational research by encouraging cooperation between scientists engaged in basic research and clinicians.