Sherin Devaskar's laboratory is focused on 1) the developmental aspects of substrate transporters, investigations ranging from molecular and cellular mechanisms, temporal and spatial distribution, to physiology, and 2) the developmental role of hypothalamic neuropeptides which control metabolism with relevance to "Fetal/Neonatal Origins of Adult Disease".
Devaskar's laboratory has demonstrated the developmental pattern of glucose transporter gene expression in brain, and determined the regulation by maternal diabetes, intrauterine growth retardation, hypothyroidism, and hypoxic-ischemic injury. Further examination of the transcriptional regulation of the neuronal glucose transporter demonstrated that Sp1/Sp3 play a reciprocal role. In addition, Devaskar has determined that maternal diabetes suppresses the expression of hypothalamic neuropeptide Y while uteroplacental insufficiency causes an increase. These effects lead to changes in food intake and body weight gain pattern postnatally. In addition, postnatal intervention which includes intracerebroventricular neuropeptide Y, leptin, or systemic glucocorticoid administration lead to sex-specific long term imprinting effects upon food intake, body weight gain, and metabolism, setting the stage for adult disease. Current studies revolve around 1] creation of transgenic and knock out mice to study the role of specific brain substrate transporters under stress e.g. hypoxic-ischemic injury, 2] The effect of perinatal metabolic perturbations on the adult phenotype. Specifically studies are focused on intra-uterine growth restriction and the mechanisms that lead to adult onset diabetes mellitus, obesity, and hypertension. This involves various genes, gene modifier processes, and intracellular signaling molecules that alter the ultimate phenotype. These studies will help shed light on the mechanisms responsible for the concept of "Fetal Origins of Adult Disease".
Neurohumoral regulation of body weight gain Pediatric Diabetes
Khan JY, Rajakumar RA, McKnight RA, Devaskar UP, Devaskar SU.
Developmental regulation of genes mediating murine brain glucose uptake American Journal of Physiology
Rajakumar PA, He Jing, Simmons RA, Devaskar SU.
Effect of uteroplacental insufficiency upon brain neuropeptide Y and corticotropin-releasing factor gene expression and concentrations Pediatric Research
Rajakumar RA, Thamotharan S, Menon RK, Devaskar SU.
Sp1 and Sp3 regulate transcriptional activity of the facilitative glucose transporter isoform-3 gene in mammalian neuroblasts and trophoblasts J. Biological Chemistry