Ph.D., Cornell University, 2000
Postdoctoral Fellow, University of California at San Diego, 2000-2003
Research Associate, The Scripps Research Institute, 2003-2007
Email address: mk24(at)indiana.edu
What determines cerebral cortex size and structure during development and across evolution? How are cell proliferation, differentiation, death and migration regulated during development to generate a functional cerebral cortex? Our research addresses these questions by examining the role of a class of lipid molecules, called lysophospholipids, which together with their G-protein coupled receptors, regulate the formation of the cerebral cortex during development. Using a whole brain culture system, we are able to examine how exposure to these lipids alters cortical size and anatomy via changes in neurogenic processes (i.e. differentiation, cell death). By studying these processes, we also hope to gain insight into how developmental disorders of cerebral cortex formation arise, such as microcephaly (small brain), polymicrogyria (many cortical folds) and lissencephaly (smooth brain), as well as what may be the mechanisms of cerebral cortical expansion across evolution.
In addition, we are interested in developmental mechanisms that increase cortical cell diversity. While early work focused on the role of incoming sensory thalamic afferents in the specification of cortical cells and areas, more recent work has identified a source of genetic variation in neurons, termed aneuploidy (i.e. the loss and gain of whole chromosomes). While it has become clear that cortical cells are characterized by unique genomes, it is not yet known how a cell’s specific complement of chromosomes relates to the cell’s function. Are aneuploid neurons advantageous by providing genetic variation or are they disadvantageous by predisposing the brain to disease?
Kingsbury, M. A., Yung, Y. C., Peterson, S., Westra, J. and Chun, J. (2006) Aneuploidy in the normal and diseased brain. CMLS, 63, 2626-2641.
Rehen, S. K., Kingsbury, M. A., Almeida, B. S., Herr, D. R., Peterson, S. and Chun, J. (2006) A new method of embryonic culture for assessing global changes in brain organization. J. Neurosci. Methods, 158, 100-108.
Kingsbury, M. A., Friedman, B., McConnell, M. J., Rehen, S. K., Yang, A. H., Kaushal, D. and Chun, J. (2005) Aneuploid neurons are functionally active and integrated into brain circuitry. Proc. Natl. Acad. Sci. U. S. A., 102, 6143-6147.
Kingsbury, M. A., Rehen, S. K., Ye, X. and Chun, J. (2004) Genetics and cell biology of lysophosphatidic acid receptor-mediated signaling during cortical neurogenesis, J. Cell. Biochem., 92, 1004-1012.
Kingsbury, M. A., Rehen, S. K., Contos, J. J. A. Higgins, C. M. and Chun, J. (2003) Non-proliferative effects of lysophosphatidic acid enhance cortical growth and folding. Nat. Neurosci., 6, 1292-1299.
Rehen, S. K., McConnell, M. J., Kaushal, D., Kingsbury, M. A., Yang, A. H., Chun, J. (2001) Chromosomal variation in neurons of the developing and adult mammalian nervous system. Proc. Natl. Acad. Sci. U. S. A., 98: 13361-13366.