Travis Salisbury, PhD
Associate Professor
salisburyt@marshall.edu

Research Interest

I have 12 years of experience in studies on regulation of gene expression in response to signaling. My work on regulated gene expression started during my postdoctoral training. My research identified that gonadotropin releasing hormone (GnRH), which signals through a G protein coupled receptor (GPCR), regulates gene expression by activating the transcriptional coactivator β-catenin. Finding that GPCR signaling regulated β- catenin activity was novel, because β-catenin had historically been associated with the developmental Wnt signaling pathway. Currently, I supervise an active laboratory, teach medical and graduate students and I was promoted to associate professor with tenure in 2015. My work remains focused on signal-regulated gene expression. Our recent studies have identified that the aryl hydrocarbon receptor (AHR), which is a ligandactivated transcription factor, responds to and mediates signaling pathways in breast cancer cells including insulin like growth factor 2 (IGF2), tumor necrosis factor (TNF) and adipokines. Evidence that IGF2, TNF, and adipokines signal through AHR is an important shift in its role, considering that AHR is best known for mediating the toxic and gene expression effects of the environmental toxicant TCDD.

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.