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bugra@boun.edu.tr

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Araştırma: Retinal development group

The research interest of the group centers around the roles of Fibroblast Growth Factor (FGF) family and dissection of the FGF signaling pathway in the context of physiopathology of vertebrate retina.

Our work on relative abundance of the FGF9 transcripts in postnatal retina suggests that the factor might be involved in the early events of retinal development such as birth, migration and differentiation of retinal cells. Histochemical studies indicate that in adult, FGF9 is mainly localized to the photoreceptor cells. While retinal Muller cells appear to devoid of the factor, its high affinity receptors are present, suggesting a paracrine mode of action.
In cultured Müller cells we have shown that FGF stimulation leads to the activation of Erk1/2, and to a smaller extent, AKT pathways and we observe enhanced proliferation.

As Müller cell proliferation is common in disease and injury related pathologies, to understand its regulation is of importance. Our recent results raise the possibility of SIK2, a serine/threonine kinase, to be an integral part of FGF signal transduction in Müller glia. We propose that threonine /serine phosphorylation status define the activity of SIK2 and the protein in active state acts as an element of a feedback mechanism in Erk1/ and Akt pathways through putative substrates Gab1 and Raf-1.

Müller cells reported to undergo apoptosis by inactivation of AKT when cultured under chronic hyperglycemic conditions. Our preliminary data implicates enhanced SIK2 activity in hyperglycemia-induced AKT inactivation in these cells.

shRNA and overexpression studies are underway to test these hypotheses.