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The mammalian suprachiasmatic nuclei (SCN) coordinates organismic function with the diurnal light/dark cycle. My laboratory investigates 1) functional organization of the circadian timing system and mechanisms of glutamatergic signaling in the SCN, and 2) functions of circadian clock genes in peripheral tissues, specifically their roles in regulating cellular responses to environmental toxins and in carcinogenesis.
Glutamatergic Regulation of SCN Neurons
This project focuses on glutamatergic signal transduction. Specifically, we are interested in mechanisms that allow SCN neurons to survive excitotoxic stress. This project focuses on the role of circadian clock state and intracellular calcium regulation of downstream targets that include caspases, anti-apoptotic factors and core clock components.
Effects of Dioxins on Circadian Timing Mechanisms
Persistent activation of AhR by dioxins disrupts liver and reproductive function, and causes multi-site carcinogenesis.
We hypothesize that dysregulation of circadian clock genes underlies pathologies associated with dioxin exposure. We are exploring regulation of the circadian clock genes, Per1 and Per2, by AhR in reproductive tissues (GnRH neurons and ovarian granulosa cells) and in tumor cells.
Representative Publications:
Tischkau SA, Mitchell JW, Pace LA, Barnes JW, Gillette MU. Protein kinase G type II is required for night-to-day progression of the mammalian circadian clock. Neuron 43(4):539-549, 2004.
Tischkau SA, Gillette MU. Oligodeoxynucleotide methods for analyzing the circadian clock in the suprachiasmatic nucleus.
Methods Enzymol 393:593-610, 2005.
Karman BN, Tischkau SA. Circadian clock gene expression in the ovary: effects of luteinizing hormone. Biol Reprod 75(4):624-632, 2006.
Mukai M, Tischkau SA. Effects of tryptophan photoproducts in the circadian timing system: searching for a physiological role for aryl hydrocarbon receptor. Toxicol Sci 95:172-181, 2007.
Cariboni A, Hickok J, Rakic S, Andrews W, Maggi R, Tischkau SA and JG Parnavelas. Neuropilins and their ligands are important in the migration of gonadotropin-releasing hormone neurons.J. Neurosci. 27(9):2387-2395, 2007.
Tischkau SA, JA Cohen, JT Stark, KM Bottum and DR Gross. Time-of-Day Affects Expression of Hippocampal Markers for Ischemic Damage Induced by Global Ischemia. Exp. Neurol. (In Press), 2007. |
