Mulligan, Kimberly - California State University, Sacramento

研究领域

My lab is interested in understanding how genes and non-heritable environmental factors may converge to cause neurodevelopmental disorders, like autism spectrum disorders (ASD). ASD are a group of heterogeneous neurodevelopmental disorders defined by mild to severe impairments in communication, behavior, and social interactions. The prevalence of ASD has increased considerably over the past several decades, and the annual cost in the U.S. has more than tripled since 2006 to over $126 billion/year in 2012. Currently, 1 in every 68 children born in the U.S. are diagnosed with ASD. ASD is a highly heritable complex disorder. Current estimates suggest dozens of genes contribute to the development of ASD. There is also mounting evidence that ASD is a multifactorial disorder that is often caused when multiple genes and environmental (epigenetic) factors converge to affect the normal neurodevelopmental program during prenatal brain development. The identification of epigenetic factors that confer risk to ASD and analysis of their molecular mechanisms could provide measures to prevent or decrease the severity of ASD. In our lab, we use the fruit fly Drosophila melanogaster to identify and examine candidate environmental chemicals to determine if they can impair neural development in flies that have genetic mutations associated with ASD. It is estimated that 75% of the genes associated with human disease are conserved in Drosophila, and they have already served as a model organism for the study of genes implicated in ASD in humans. Indeed, mutating ASD susceptibility genes in flies can cause measurable social and behavioral deficits in the mutant flies. Fruit flies are also incredibly easy to manipulate genetically, making them ideal for the study of multiple genetic mutations in the same organism. There are a number of well-defined behavioral assays, one of the most prominent being the courtship assay. (Flies have specific, stereotyped behaviors they perform during courtship and alteration in these behaviors is often indicative of a change in neural circuitry.) If behavioral changes are detected in adult flies, brains and neurons can be examined to elucidate the mechanism by which a particular chemical alters brain development. Finally, fruit flies have a generation time from egg to adult of 9 days, so meaningful data can be generated relatively quickly; this is critical given the urgent need to understand the causes ASD.

近期论文

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Mulligan K and Cheyette B (2017) “Neurodevelopmental Perspectives on Wnt Signaling in Psychiatry.” Review. Mol Neuropsychiatry. Jan 13. (2) 219-246 Mulligan K and Cheyette B (2016) “Introduction to Wnt signaling”, Chapter for Inborn Errors of Development, 3rd Edition, Oxford University Press Martin P, Stanley R, Ross A, Freitas A, Moyer C, Brumback A, Iafrati J, Stapornwongkul K, Dominguez S, Kivimae S, Mulligan K, Pirooznia M, McCombie W, Potash J, Zandi P, Purcell S, Sanders S, Zuo Y, Sohal V, Cheyette B (2016) "DIXDC1 contributes to psychiatric susceptibility by regulating dendritic spine and glutamatergic synapse density via GSK3 and Wnt/β-catenin signaling" Mol Psychiatry. Oct 18. doi: 10.1038 Mulligan K and Cheyette B (2012) “Wnt signaling in vertebrate neural development and function” Review. J NeuroImmune Pharmacol. Dec; 7(4) 774-87 Mulligan K, Fuerer C, Ching W, Willert K, Fish M, Nusse R (2012) “Secreted-Wingless interacting molecule (Swim) promotes long-range signaling by maintaining Wingless solubility” Proc Natl Acad Sci USA. Jan10;109(2):370-7 Nusse R, Fuerer C, Ching W, Harnish K*, Logan C, Zeng A, ten Berge D, Kalani Y. (2008) “Wnt signaling and stem cell control” Cold Spring Harb Symp Quant Biol. Nov (73) 59-66. Review Johnson ML, Harnish K*, Nusse R, Van Hul W (2004) “LRP5 and Wnt signaling: a union made for bone.” J Bone Mineral Research. Nov;19(11):1749-57. Review