Cellular and Molecular Pharmacology Discipline

Patricia Loomis graduated from Cedar Crest College in Allentown, Pennsylvania in 1987. She earned the PhD degree from the University of Alabama at Birmingham in 1994. Following postdoctoral work at Northwestern University and the Chicago Medical School she was appointed Research Assistant Professor of Cellular and Molecular Pharmacology at the Chicago Medical School in 2006. Patty also serves as director of Confocal Microscopy Laboratory and co-director of the Live Cell Imaging Facility.

Research

Although great strides have been made in the study of auditory hair cell stereocilia, the molecular mechanisms controlling the assembly and maintenance of this exquisite example of cytoarchitecture are poorly understood. The Espin family of proteins, which have been implicated in deafness and vestibular dysfunction in humans and mice, are an integral component of this actin cytoskeletal regulatory system. Encoded by a single gene (Espn), the Espins share a C-terminus that is necessary and sufficient for actin bundling activity. While the C-terminus bestows Espins with the classification of actin bundling proteins, the N-terminus, with its diverse functional domains generated by differential start site selection and alternative splicing, imparts upon Espins the recognition as multifunctional actin cytoskeletal regulatory proteins. Which factors are responsible for the regulation of isoform selection and the downstream significance with regard to isoform localization and the ensuing effects on the organization, dynamics and signaling capabilities of bound F-actin during the development and maturation of the inner ear are still unknown. To begin to understand how Espin gene expression is controlled at the level of RNA processing, I am testing the hypothesis that both regulatory sequences on the pre-mRNA and the trans-acting proteins which bind them act in concert to modulate splice site selection in both a mouse and zebra fish model system.

Once severely damaged, human auditory hair cells cannot regenerate. However, gene therapy has the promise of applying genomics-based treatments to aid these cells and possibly restore hearing. Effective application of gene therapy demands that we understand how genes such as Espn are involved in the development of the inner ear and how the proteins encoded by them act in concert to maintain this elaborate cytoarchitecture. Dissection of the processes of alternative splicing of Espin pre-mRNA will further our understanding of how hair cells within the inner ear regulate the complex spatiotemporal patterns of expression of this important family of actin-interacting proteins.

Publications

MPTP administration in mice changes the ratio of splice isoforms of fosB and rgs9. Brain Res. 2007 Nov 28;1182:1-10. Epub 2007 Sep 14.

Regulation of retention of FosB intron 4 by PTB. PLoS ONE. 2007 Sep 5;2(9):e828.

Espins and the actin cytoskeleton of hair cell stereocilia and sensory cell microvilli. Cell Mol Life Sci. 2006 Oct;63(19-20):2329-41. Review.

Targeted wild-type and jerker espins reveal a novel, WH2-domain-dependent way to make actin bundles in cells. J Cell Sci. 2006 Apr 15;119(Pt 8):1655-65. Epub 2006 Mar 28.

Espins are multifunctional actin cytoskeletal regulatory proteins in the microvilli of chemosensory and mechanosensory cells. J Neurosci. 2004 Jun 9;24(23):5445-56.

Cdk5 regulates axonal transport and phosphorylation of neurofilaments in cultured neurons. J Cell Sci. 2004 Feb 29;117(Pt 6):933-41. Epub 2004 Feb 3.

Espin cross-links cause the elongation of microvillus-type parallel actin bundles in vivo. J Cell Biol. 2003 Dec 8;163(5):1045-55. Epub 2003 Dec 1.

Rapid transport of neural intermediate filament protein. J Cell Sci. 2003 Jun 1;116(Pt 11):2345-59. Epub 2003 Apr 23.

Novel espin actin-bundling proteins are localized to Purkinje cell dendritic spines and bind the Src homology 3 adapter protein insulin receptor substrate p53. J Neurosci. 2003 Feb 15;23(4):1310-9.

Loomis, PA and Goldman, RD. Neural intermediate filament systems. Encyclop. of Neuroscience. 2 nd Revised Edition 1998, edited by George Adelman and Barry H. Smith. pp.1313-1316.

Loomis , PA Isolation of dorsal root ganglia from chick embryos. Cells – A Laboratory Manual. Edited by DL Spector, RD Goldman and LA Leinwand. Cold Spring Harbor Laboratory Press 1998, vol 1. pp 9.8-9.13.

Alterations in neural intermediate filament organization: functional implications and the induction of pathological changes related to motor neuron disease. J Cell Sci. 1996 Sep;109 ( Pt 9):2319-29.

A novel tau transcript in cultured human neuroblastoma cells expressing nuclear tau. J Cell Biol. 1993 Apr;121(2):257-67.

Identification of nuclear tau isoforms in human neuroblastoma cells. Proc Natl Acad Sci U S A. 1990 Nov;87(21):8422-6.