I received my PhD in Neuropharmacology from the University of Maryland, Baltimore. I then spent three years as a post-doctoral fellow in the Laboratory of Neurobiology and Behavior at the Rockefeller University in New York, NY. In 2003, I was selected as a NIH BIRCWH (Building Interdisciplinary Research Careers in Women's Health) Scholar by the Women's Health Research Group at the University of Maryland and joined the faculty as a member of the Department of Pharmacology and Experimental Therapeutics. I am a member of the University of Maryland Graduate School. I am also a member of the Society for Behavioral Neuroendocrinology and the American Association of Anatomists.
My laboratory is interested in the effects of gonadal steroids on neuronal-glial interactions in the developing and adult brain and how these steroid mediated interactions affect gene expression, cellular mechanisms, and ultimately, behavior of the animal. High-density oligonucleotide microarrays have been instrumental in our identification of steroid regulated genes. One of the more interesting regulations is prostaglandin D synthase (L-PGDS), a non-neuronal enzyme that catalyzes the conversion of Prostaglandin H2 to Prostaglandin D2 (PGD2). PGD2 is significantly involved in the induction of sleep. Sleep patterns are sexually dimorphic and data from a number of different species including humans suggests that sex hormones influence the physiology and pathology of sleep. In female rodents, sleep is reduced while locomotion is increased when estradiol (E2) levels are highest. The preoptic region is a key site for estrogenic regulation of these functions. However, molecular mechanisms by which E2 acts to reduce sleep and increase activity are unclear. My work demonstrated a 2-fold reduction in L-PGDS transcript levels, following E2 treatment. The reduction in L-PGDS occurs in the ventrolateral preoptic area (VLPO), a putative sleep center where PGD2 is believed to be an endogenous somnogen. In sleeping rodents, the VLPO contains a population of sleep-active neurons as defined by FOS expression and microinjections of PGD2 not only induces sleep but increases the expression of FOS in the VLPO . Thus, we hypothesize that decreases in PGD2 in the VLPO may contribute to generalized arousal and decreased sleep mediated by estrogens. In fact, we recently showed that the suppression of functional L-PGDS mRNA transcripts in the VLPO leads to heightened arousal. Ovariectomized female mice microinjected in the preoptic area with a novel antisense moiety, â€œlocked nucleic acidsâ€, show heightened arousal following controlled application of sensory stimuli. The level of arousal was not significantly different from animals that were treated with E2. Reducing L-PGDS in the VLPO of females lacking ovarian steroids mimic the effect of E2 on activity and arousal, and represents a novel molecular pathway through which E2 may modulate these functions. Our present arousal assay has allowed us to demonstrate that (1) E2 or (2) a reduction in L-PGDS protein results in a level of increased alertness which would suggest that the animal's sleep-drive is decreased. However, these observation are correlative, and thus it is unknown if E2 modulation of L-PGDS expression affects sleep homeostasis. The broad goal of this research project is to begin to elucidate the role of L-PGDS in the molecular and cellular mechanisms underlying the effects of gonadal steroids on sleep. An understanding of how changes in ovarian hormone levels affect sleep is particularly relevant to peri- and postmenopausal women who report disturbances in their sleep patterns.
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