Dr. Garcia-Ocaña’s research interest has focused over the years on tissue regeneration, growth factors and intracellular signaling. More specifically, his group is analyzing the therapeutic potential of growth promoting agents to induce pancreatic beta cell regeneration in diabetes. He described for the first time that expression of hepatocyte growth factor (HGF) in vivo in the beta cell markedly increases beta cell proliferation, survival, function and mass in transgenic mice. In addition, he also demonstrated the beneficial effects of HGF on improving islet transplant outcomes. These novel results highlighted the potential of growth factors, and in particular HGF, for beta cell regeneration and replacement therapies in diabetes.
His group has also identified the intracellular signaling pathways involved in the beneficial effects of growth factors in beta cells. They have found that the Akt pathway is required for the anti-apoptotic effects of HGF and that activation of this pathway is enough to improve long-term human islet engraftment and survival in mice without adverse effects. They have also found that protein kinase C (PKC) ζ is a key and novel signaling pathway involved in growth factor-induced beta cell replication. Activation of PKC ζ leads to markedly increased rodent beta cell expansion and more importantly human beta cell replication. In addition, activation of PKC ζ enhances insulin expression and secretion. These findings highlight this pathway as an attractive target for beta cell regeneration.
Recently, he has also centered his interest on the physiological roles of HGF and PKC ζ in the beta cell. Using genetically-modified mouse models, he has shown that the absence of HGF sgnaling in beta cells leads to the development of gestational diabetes. These results open the door to important translational studies in pregnant women with gestational diabetes, an aspect currently being explored by Dr. Garcia-Ocana in collaboration with Dr. Carol Levy. We believe that the knowledge obtained from these studies can lead to the development of future effective therapies to increase beta cell regeneration, to improve beta cell replacement and to expand beta cell mass for diabetes.
