Department: Pharmacology, Physiology, and Toxicology
Research Cluster: Toxicology and Environmental Health Sciences
Office: BBSC 336-J | Laboratory: BBSC 309
Phone: (304) 696-7314
Dioxins are a family of fat soluble pollutants found in the environment due to their stability, municipal waste incineration, and the manufacture of herbicides and pesticides – resulting in levels of this chemical that range from parts per trillion to parts per billion in humans. While it is clear that this family of endocrine disrupting chemicals (EDCs) have a potent deleterious effect on wildlife species, their impact on human health is still a controversial subject. This lack of clarity is due, at least in part, to too few human studies, and a need for a deeper mechanistic understanding of how exposure to pollutants – like dioxins – may impact human health. As detailed below, I am interested in understanding the mechanism of endocrine disruptor action in the ovary and breast.
We, and others, have reported that fetal exposure to dioxins has a striking negative effect on adult female reproduction. While these findings suggest that prenatal exposure to this endocrine disrupting chemical leaves a deleterious imprint in the ovary leading to reduced fertility and steroidogenesis in adult life, the mechanism is not understood. Consequently, one of our objectives is to adopt and optimize techniques that will purify ovarian follicles from mouse ovaries and recapitulate folliculogenesis in vitro to delineate the site of endocrine disruptor action in the ovary and to determine if this disruptive event is due to an epigenetic DNA modification.
We are also interested in signaling cross-talk between endocrine disrupting chemicals and endogenous hormones. While prior reports have focused on signaling cross-talk between dioxins and estrogen, our preliminary data suggests that dioxins may also cross talk with hormones that signaling through G protein coupled receptors. Currently, we are studying whether a pituitary hormone, follicle-stimulating hormone (FSH), can modulate the toxicity of dioxins in the ovary. Lastly, we are interested in how exposure to dioxins may impact the efficacy of anti-cancer drugs that target the estrogen receptor in breast tissue.
Salisbury TB, Tomblin JK, Primerano DA, Boskovic G, Fan J, Mehmi I, Fletcher J, Santanam N, Hurn E, Morris GZ, Denvir J. Endogenous aryl hydrocarbon receptor promotes basal and inducible expression of tumor necrosis factor target genes in MCF-7 cancer cells. Biochem Pharmacol. 2014 Oct 1;91(3):390-9.
Justin Tomblin, Travis B. Salisbury. Insulin like growth factor 2 regulation of aryl hydrocarbon receptor in MCF-7 breast cancer cells. Biochem Biophys Res Commun. 2014 Jan 17;443(3):1092-6.
Travis B. Salisbury, Gary Z. Morris, Justin K. Tomblin, Ateeq R. Chaudhry, Carla R. Cook, and Nalini Santanam. Aryl hydrocarbon receptor ligands inhibit IGF-II and adipokine stimulated breast cancer cell proliferation. ISRN Endocrinol. 2013 Sep 23;2013:104850. doi: 10.1155/2013/104850.
Salisbury TB, Binder AK, Grammer JC, Nilson JH. GnRH regulated expression of Jun and JUN target genes in gonadotropes require a functional interaction between TCF/LEF family members and β-catenin. Mol Endocrinol. Molecular Endocrinology 2009 Mar;23(3):402-11
Salisbury TB, Binder AK, Nilson JH. Welcoming beta-catenin to the gonadotropin-releasing hormone transcriptional network in gonadotropes. Molecular Endocrinology 2008 Jun; 22(6):1295-303.
Salisbury TB, Binder AK, Grammer JC, Nilson JH. Maximal activity of the luteinizing hormone beta-subunit gene requires beta-catenin. Molecular Endocrinology 2007 Apr; 21(4): 963- 71.
Justin Tomblin, Ph.D. student
Ateeq Chadry, Marshall undergraduate student