The overall goal of the Mahoney lab is to determine when and how endocrine signals regulate biological rhythms.
My innovative research brings together the fields of chronobiology, reproductive biology, and neurotoxicology. Biological rhythms are essential for life as they underlie a myriad of physiological processes from the sleep-wake cycle, metabolism, and immune function, to reproductive cyclicity and hormone secretion. I examine the influence of estradiol, estrogen receptor agonists, botanicals, and endocrine disrupting chemicals on daily sleep-wake activity patterns, the behavioral and neural responses to light signals, and rhythms in protein and mRNA levels. My research is important as it addresses basic scientific questions such as:
- When and how do changes in hormone signals program the adult timekeeping system?
- How are sex differences in circadian rhythms regulated by circulating hormones?
My lab has been the first to characterize when and how estrogen signaling mechanisms regulate the expression o behavioral and neural circadian rhythms. This worked has gained attention in the field and I have been an invited contributor to several review articles on women’s health and estrogen, and an invited speaker at national conferences. My work brings a new perspective to understanding how sex differences and hormones regulate biological rhythms in humans and other species. Below are some descriptions of some major projects in the lab.
Project 1: Analyze the impact of endocrine mimics and antagonists on biological rhythms
My research is also applicable to human health concerns by determining how environmental contaminants impact the timekeeping system. We are examining how compounds in the environment (phthalates) or in food which mimic estrogen (BPA, genistein) alter circadian rhythms. We are the first to demonstrate that phthalates alter activity levels, distribution of activity across the LD cycle, as well as gene expression in the brain’s master clock. We will expand on this research by examining the developmental impact of these chemicals on clock gene expression in the master clock, and by examining the impacts of additional chemical compounds. These data are significant because they have implications for understanding the impact of environmental toxicants on the fundamental timekeeping system.
Project 2: Assess the impact of environmental exposures on anxiety behaviors and reproductive behaviors in mice.
Phthalates are common plasticizers used in food containers, fragrances, personal care products, and medical tubing. We are investigating how these chemicals, either as a single metabolite or in environmentally relevant mixtures, can alter anxiety like behaviors in mice. In parallel we are also examining gene expression changes in brain areas that regulate anxiety.
In a second major project we are testing the hypothesis that developmental exposure to a phthalate mixture decreases fertility by having an adverse impact on sexually dimorphic brain areas and reproductive behaviors. We are using behavioral tests to assess if reproductive behaviors such as partner preference, female responsivity, and attractiveness of mice is altered by these exposures.
Project 3: Assess the impact of environmental exposures on sleep quality, depression, and hormone levels in midlife women.
In collaboration with clinical researchers and epidemiologists our lab examines how environmental exposures to endocrine disrupting chemicals modifies sleep quality, depressive symptoms, and reproductive hormone concentrations in women undergoing the menopausal transition. Over 40% of perimenopausal women report sleep disruptions, however, the factors that impact sleep quality still remain widely unknown. Hypothalamic-pituitary-ovarian axis hormones, including estradiol and progesterone, are disrupted during aging and the perimenopausal transition, and their disruption has been linked to increase sleep disturbances and depression. However, it is unclear whether environmental exposures that may disrupt and/or mimic these hormones has an impact on sleep or depression in midlife women. Importantly, women are often exposed at higher levels to chemicals found in personal care products when compared to age-matched men, making them more susceptible to the endocrine disrupting properties of these chemicals. Our lab aims to close these gaps by investigating the impact of environmental exposures and hormone concentrations on sleep quality and depression. This crucial and unique work will identify factors that modulate major menopausal symptoms, including sleep quality and depression, thereby identifying potential therapeutic targets to improve the quality of life of aging women.
Project 4: Assess the association of environmental exposures with hyperthyroidism in cats
In collaboration with toxicologists and board certified veterinarians, we are looking at the relationship of phthalate metabolites to the occurrence of hyperthyroidism in pet cats.