MARILYN L. GETCHELL, Ph.D.

MARILYN L. GETCHELL, Ph.D.
Northwestern University (1971)
Postdoctoral Training at Monell Chemical Senses Center, University of Pennsylvania and John B. Pierce Foundation, Yale University School of Medicine
Professor of Anatomy and Neurobiology.

Research Interests: Neuronal Cell Death and Neurogenesis in the Peripheral Olfactory System: The Impact of Aging and Neurodegenerative Disease

Our research focuses on understanding cellular and molecular age-related changes in olfactory receptor neurons, their progenitor cells in the olfactory epithelium, and their synaptic targets, mitral cells in the olfactory bulb. Olfactory ability declines with increasing age and is substantially impaired in certain neurodegenerative diseases such as Alzheimer’s disease. This decline may be due to an increased rate of cellular damage and death in mature olfactory receptor neurons, impairment in the process of neurogenesis by which olfactory receptor neurons are replaced throughout life, or a complex interaction between these two processes.

In human olfactory tissue from individuals with Alzheimer’s disease and from age-matched non-demented elderly controls, we are identifying molecular indicators of oxidative stress and correlating their levels and localization with the numbers and localization of dying olfactory receptor and bulbar neurons. By characterizing changes in relevant oxidative stress markers and correlating their levels and sites of occurrence with neuronal death, we may be able to utilize the peripheral olfactory system as a "window" into the central nervous system for evaluating the progression of neuropathology and for monitoring the efficacy of therapeutic interventions in Alzheimer’s patients.

Utilizing transgenic mouse models, we are investigating the impact of aging on several growth factors and cytokines that regulate neurogenesis from progenitor cells in the olfactory epithelium. Our current studies are focused on analyses of changes in gene expression following target ablation, which induces a synchronous wave of apoptosis, macrophage infiltration, and neurogenesis. We are using state-of-the-art cellular and molecular techniques, including genomic analyses and real-time RT-PCR, to investigate gene regulation during these events and how gene expression is modified in the remodeling olfactory epithelium with advancing age.

Chuah, M.I., and M.L. Getchell. Metallothionein in olfactory mucosa of Alzheimer’s disease patients and ApoE deficient mice. NeuroReport. 10:1919-1924, 1999.

Getchell, T.V., Narla, Rama Krishna, Little, S., Hyde, J.F., Getchell, M.L. Horizontal basal cell proliferation in the olfactory epithelium of transforming growth factor-a transgenic mice. Cell and Tissue Research 299:185-192 (2000).

Nan , B., M.L. Getchell, J. Partin, and T.V. Getchell. Leukemia inhibitory factor, interleukin-6, and their receptors are expressed transiently in the olfactory mucosa after target ablation. Journal of Comparative Neurology. 435: 60-77, 2001.

Getchell, T.V., D.S. Shah, J.V. Partin, N.K. Subhedar, and M.L. Getchell. Leukemia inhibitory factor mRNA expression is upregulated in macrophages and olfactory receptor neurons after target ablation. Journal of Neuroscience Research. 67: 246-254, 2002.

Getchell, M.L., M Boggess, S Pruden II, S Little, S Buch , and TV Getchell. Expression of TGF-b type II receptors in the olfactory epithelium and their regulation in TGF-a transgenic mice. Brain Research 945:232-241, 2002.

Getchell, T.V., NK Subhedar, DS Shah, G Hackley, JV Partin, G Sen, ML Getchell. Chemokine regulation of macrophage recruitment into the olfactory epithelium following target ablation: involvement of MIP-1a and MCP-1. Journal of. Neuroscience Research. 70:784-793,2002.

Getchell, T.V., X Peng, AJ Stromberg, K-C Chen, CP Green, NK Subhedar, DS Shah, MP Mattson, and ML Getchell, M.L. Age-related trends in gene expression in the chemosensory-nasal mucosae of senescence-accelerated mice. Ageing Research Reviews 2:211-243, 2003.

Getchell, M.L., DS Shah, SK Buch, DG Davis, TV Getchell. 3-Nitrotyrosine immunoreactivity in olfactory receptor neurons: Implications for impaired odor sensitivity. Neurobiology of Aging 24:663-673, 2003.

Getchell, T.V., Peng, X., Green, C.P., Stromberg, A.J., Chen, K-C., Mattson, M.P., Getchell, M.L. In silico analysis of gene expression profiles in the aging olfactory-nasal mucosae of senescence-accelerated mice. J. Neurosci. Res. 77:430-452 (2004).

Kwong, K., Vaishnav, R.A., Liu, Y., Subhedar, N., Stromberg, A.J., Getchell, M.L., Getchell, T.V. Target ablation-induced regulation of macrophage recruitment into the olfactory epithelium of Mip-1a^-/- mice and restoration of function by exogenous MIP-1a. Physiol. Genomics 20:73-86, 2004.

Li, H., Wood, C.L., Getchell, T.V., Getchell, M.L., Stromberg, A.J. Analysis of oligonucleotide array experiments with repeated measures using mixed models. BMC Bioinformatics 5: 209-220, 2004.

Getchell, T.V., Liu, H., Vaishnav, R., Kwong, K., Stromberg, A.J., Getchell, M.L. Temporal profiling of gene expression during neurogenesis and remodeling in the olfactory epithelium at short intervals after target ablation. J.Neurosci. Res. 80:309–329, 2005.

Poon, H.F. ,Vaishnav, R.A., Butterfield, D.A., Getchell, M.L., Getchell, T.V. Proteomic identification of differentially expressed proteins in the aging murine olfactory system and transcriptional analysis of the associated genes. J. Neurochem. 94:380-392, 2005.

Liu, H., Tarima,S., Borders, A.S., Getchell, T.V., Getchell, M.L., Stromberg,A.J. Quadratic regression analysis for gene discovery and pattern recognition for small sample non-cyclic microarray time-course experiments. BMC Bioinformatics 6:106-122, 2005.

Poon, H.F., Vaishnav, R.A., Getchell, T.V., Getchell, M.L., Butterfield, D.A. Quantitative proteomics analysis of differential protein expression and oxidative modification of specific proteins in the brains of old mice. Neurobiol. Aging (in press, on-line 6/23/05).