HONORS AND AWARDS:
2001: Medical Guild Departmental Competition, University of
Florida, Gainesville FL
2003: Graduate Student Competition Award-Pollutant Responses in
Marine Organisms (PRIMO)
2003: NIEHS Postdoctoral Fellowship, University of Vermont
2003: Patent for Largemouth bass gene chip, University of Florida (EcoArray
Inc.)
2004: Postdoctoral Vermont Cancer Center Award, University of
Vermont
RESEARCH
INTERESTS:
• Cell signaling pathways
impacted by airborne pollutants (asbestos, smoke,
nanoparticles) relevant to environmental lung disease
• The role of estrogen in lung cancer
• Molecular mechanisms of xenoestrogens in aquatic
models (zebrafish)
Airborne pollutants and environmental lung disease
Occupational and environmental exposure to airborne
pollutants is associated with the development of chronic
lung disease including cancer, fibrosis, bronchitis, and
asthma, among others. The molecular pathways perturbed
by these pollutants (asbestos, smoke, nanoparticles) is
not clear, and elucidation of these signaling cascades
and control of critical downstream gene targets in lung
cells is the focus of my research.
Using a toxicogenomic approach, we have discovered
several candidate genes (MUCs and Clca1) that may be
important in particulate-induced lung disease and are
specifically involved in the production and regulation
of mucin secretion in the lung. Airway mucus
hypersecretion is a prominent feature of chronic lung
pathologies, and elucidation of signaling pathways
stimulated by airborne pollutants that regulate mucus
metaplasia will lead to both a better understanding of
basic biology of chronic pulmonary diseases as well as
potential therapeutic targets. We are currently
investigating the role of EGFR/MAPK signaling pathways
in the transcriptional regulation of these genes through
in vitro and in vivo applications including microarrays,
siRNA, chemical inhibition studies, immunohistochemistry,
and transgenic animals.
In a related focus, we are also investigating the role
of estrogen receptors in lung disease. The increasing
incidence of female non-smokers with lung cancer (adenocarcinoma)
has led to speculation that estrogen plays a role in
disease development and/or progression. Estrogen
receptors have been recently discovered in the lung and
are overexpressed in some tumors, but the role they play
in regulation of cell growth, death, metastasis, and
therapeutic resistance is currently unknown.
Endocrine disruption in aquatic model systems
Many estrogen active compounds (xenoestrogens),
including components of pesticides, herbicides,
insecticides, industrial chemicals, and pharmaceuticals
have been causally associated with adverse effects on
wildlife and human populations, contributing to impaired
reproductive success, developmental abnormalities, and
cancer incidence. Xenoestrogens bind and activate
estrogen receptors, which are transcription factors that
regulate downstream gene targets involved in growth,
reproduction, and development. Estrogen signaling
pathways have become increasingly complex with the
discovery of additional receptor subtypes,
a
and
b.
Investigating the functional roles of the receptor
isotypes in aquatic models (zebrafish) in response to
estrogen and environmental contaminants is currently
underway using molecular techniques including
microarrays and morpholino knockdown.
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PUBLICATIONS:
Sabo-Attwood, T., Larkin, P., Kelso, J., and Denslow,
N.D. (2002) Gene expression profiles of largemouth bass
exposed to nonylphenol and ICI 182,780. Endocrine
Disruptors: Mechanisms and Impacts, International
Congress on the Biology of Fish, 17-28.
Larkin, P., Sabo-Attwood, T., Kelso, J.,
and Denslow, N. (2002) Gene expression analysis of largemouth bass
to estradiol, nonylphenol, and p,p'-DDE. Comparative Biochemistry
and Physiology Special Issue, Functional Genomics, 133,
543-557.
Larkin, P., Sabo-Attwood, T., Kelso,
J., and Denslow, ND. (2003) Analysis of gene expression profiles in
largemouth bass exposed to the endogenous hormone, estradiol, and
the environmental contaminants, nonylphenol, and p, p'-DDE.
EcoToxicology 12, 463-468.
Sabo-Attwood, T., Kroll, KJ, and
Denslow, N.D. (2004) Differential Expression of Largemouth Bass
Estrogen Receptor Isotypes Alpha, Beta, and Gamma By Estradiol.
Molecular and Cellular Endocrinology 218, 107-118.
Ramos-Nino, ME, Vianale, G.,
Sabo-Atwood, T., Mutti, L., and Mossman, B.T. (2004) Human
Mesothelioma Cells Exhibit Tumor Cell-Specific Differences in
Phosphatidylinositol 3-kinase/AKT Activity that Predict the Efficacy
of Onconase. Molecular Cancer Therapeutics 2005; 4(5).
Sabo-Attwood, T., Ramos, M.E., Bond,
J., Butnor, K., Heintz, N., Gruber, A., Vacek, P., and Mossman, B.T.
(2005) Gene Expression Profiles Reveal Increased mCLCA3 Expression
and Mucus Metaplasia in a Murine Model of Asbestos-Induced
Fibrogenesis. Am J Pathol. 2005 Nov;167(5):1243-56.
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