Al-Nakkash Lab

Project I:  Understanding the role that genistein (a naturally occuring phytoestrogen) has to play in the regulation of  transpithelial secretion in murine jejunum, and elucidating it's mechanism(s) of action. We have previously shown that dietary genistein (600 mg genistein/kg food) increases jejunual secretion in wild-type female (not male) mice. We have also shown that genistein. administered via daily subcutaneous injections (600 mg genistein/kg body weight/day) mediates an increase in jejunal secretion in both male and female wild-type mice. We have shown that these genistein-dependent effects are mediated by gender-dependent mechanisms: a 5% increase in the apical localization of CFTR in males, activation of ERα in males, and adenylate cyclase activation in males. Interestingly, our lab has also shown that castrated wild-type maleslose thier genistein-mediated increases in intestinal secretion, whereas ovariectomized wild type females maintain thier secretion. Current studies aim to examine the intracellular pathways involved in mediating genistein's sex-dependent effects in the presence and absence of endogenous sex hormones. This project has implications with respect to improving intestinal secretion in the cystic fibrosis (CF) mouse model. We have an ongoing project aimed to examine the effects of genistein on the R117H CF mouse. Recent studies are aimed at understanding the benefits of genistein on DF508 CF mice.

Project II:  Characterizing differences in jejunal epithelial transport (i.e transepithelial secretion) in the ob/ob mouse (a model of type II diabetes) compared to its lean littermate controls. This is a relatively new project aimed at furthering our understanding of the specific cellular transporters present in villi and crypt cells, and determining how, if at all, they may contribute to the diabetic phenotype of the ob/ob mouse.