My current NIH and NSF-funded research is on natural regulators and
toxicants, and their molecular action to alter gene expression and
cellular apoptosis, using an invertebrate model system to study molecular
mechanisms underlying these processes. One area study funded by the
National Cancer Institute is on the unusual molecular structure and action
of an apoptosis inhibitor that we have newly identified from
invertebrates, ‘deterin,’ which is a homolog of the human ‘survivin’
apoptosis inhibitor that is overexpressed in a wide variety of cancers.
Deterin and survivn are expressed in embryonic, undifferentiated tissues,
and appear to inhibit the apoptotic pathways induced by either exogenous
chemical toxicants or natural endogenous regulators. A second area of
hormone action is on the molecular structure and functional action of the
invertebrate homolog of the retinoid X receptor, ‘ultraspiracle.’
Since null mutants of this receptor are lethal, our studies, including
with transgenic organisms, are examining mechanistics questions on the
conformation of the ligand binding pocket and the receptor’s interaction
with ligand and transcriptional coregulators. Development of selective
agonists or antagonist compounds for this receptor to control invertebrate
transmitters of disease or crop pests may provide an alternative to use of
harmful pesticides in the environment that have such adverse effects on
humans and other nontarget organisms (Research ca. 70% D.O.E.).
Research Publications
Fang F, Xu Y, Jones D, Jones G. (2005)
Interactions of ultraspiracle with ecdysone receptor in the transduction
of ecdysone- and juvenile hormone-signaling. FEBS J. 272(7):1577-89.
Wozniak M, Chu Y, Fang F, Xu Y, Riddiford L, Jones D, Jones G.
(2004) Alternative farnesoid structures induce different conformational
outcomes upon the Drosophila ortholog of the retinoid X receptor,
ultraspiracle. Insect Biochem Mol Biol. 34(11):1147-62.
Xu Y, Fang F, Ludewig G, Jones G, Jones D. (2004) A mutation
found in the promoter region of the human survivin gene is correlated to
overexpression of survivin in cancer cells. DNA Cell Biol. 23(7):419-29.
Xu Y, Fang F, Chu Y, Jones D, Jones G. (2002) Activation of transcription
through the ligand-binding pocket of the orphan nuclear receptor
ultraspiracle. Eur J Biochem. 269, 6026-36.
Jiang, X., Wilford, C., Duensing, S., Munger, K., Jones, G., Jones, D.
Participation of Survivin in mitotic and apoptotic activities of normal
and tumor-derived cells. J. Cell Biochem. 83, 342 - 54
Jones, G., Jones, D., Zhou. L., Stellar, H., and Chu, Y. X. (2000)
Deterin, a new inhibitor of apoptosis from Drosophila melanogaster. J.
Biol. Chem. 29, 22157 22165
Jones, G., Wozniak, M., Chu, X. Y., Dhar, S., and Jones, D. (2001)
Juvenile hormone III dependent conformational changes of the nuclear
receptor Ultraspiracle. Insect Biochem. Molec. Biol. 32, 33-49
Jones, G., Jones, D. 2000. Considerations on the structural evidence of
a ligand -binding function of ultraspiracle, an insect homolog of
vertebrate RXR. Insect Biochem. Molec. Biol. 30, 671 -79
Jones, G, Chu, Y., Schelling, D and Jones, D. (2000) Regulation of the
juvenile hormone esterase gene by a composite core promoter. Biochem. J.
346, 233-240.
Jones, G., Manczak, M., Schelling, D., Turner, H. and Jones, D. (1998)
Transcription of the juvenile hormone esterase gene under the control of
both an initiator and AT-rich motif. Biochem. J. 335, 79-84.
Teaching
My teaching activities include course or section coordination of the
introductory and advanced Toxicology classes and lectures in those classes
on biochemical and molecular actions of natural plant, animal and
microbial toxicants. I am also teaching a class on critical review of
Toxicological literature, and how to prepare postdoctoral fellowship
grant. In the latter activity I am working with the graduate students as
they each organize, develop and write an actual grant application, to
prepare them for the real life grant exercises that they will need in
their future Toxicological careers. I am currently serving on the advisory
committees of several graduate students. (Teaching ca. 20% D.O.E.)
University and Public Service
An important public service activity related to the University was my
testimony at a legislative task force in 1991 that initiated a process by
which the state Open Records Law became amended in 1992 to give the
faculty of Kentucky public universities full access to all of their own
personnel records. My University service activities have included
participation on Senate, Medical Sector, College and Graduate Center of
Toxicology committees, including the Senate Admissions Advisory Committee,
Unit Director and Faculty Search Committees, and College Promotion and
Tenure Committee. In addition have been numerous individual service
activities to promote the increased exercise of faculty governance in
University policy-making at the University-wide level and at the level of
academic units. I also provide assistance to untenured and other faculty,
as they prepare their appeals of their denial of tenure, promotion or
other aspects of academic employment (Service ca. 10% D.O.E.)