The Mechanisms of Allostasis Conference: Stressed or Stressed Out

The goal of Kelli Church’s research program is to understand the development, organization, and activation of neural circuits that control reproductive neuroendocrine hormone activity in males and females in both normal physiologic conditions and in conditions of disrupted homeostasis, also known as stress. 

Church launched her independent research program at the University of California, San Diego, in 2013 within the Department of OBGYN and Reproductive Sciences after training with highly regarded experts in fields of molecular neuroendocrinology and reproductive physiology, Pamela Mellon, PhD, and Fred Karsch, PhD. Her curiosity in understanding mechanisms controlling reproductive neuroendocrine function began with extensive experience in the sheep model, in which the power of hypothalamic-pituitary portal sampling can be exploited. 

Applying the fundamentals of hypothesis-driven research, her current research program employs state-of-the-art chemogenic and genetic manipulations to dissect models to enhance the understanding of stress-activated neural circuits and their relation to disrupted reproduction. The work has resulted in 33 publications and is nationally and internationally regarded for innovative research into stress-activated neural circuits.

A broader impact of her research program is to train the next generation of science-minded individuals. Church has mentored three postdoctoral fellows, one graduate students, three medical students, and 13 undergraduate and high school students. She is Co-director of the UC San Diego Mentor Assistance Program (MAP), a campus-wide program matching high school students with mentors from an array of disciplines to provide a pathway for student faculty and post-doctoral fellows and staff to mentor students in their own field of interest (i.e., independent study, class projects, or possible career path).
 

Marc Tetel’s research has focused on the functions and mechanisms of action of estrogens and progestins. HIs graduate work investigated how estradiol and progesterone act in the brain to regulate female reproductive behavior. He extended this work in his post-doctoral fellowship to study molecular mechanisms of PR action in breast cancer. His research focused on how nuclear receptor coactivators, which were discovered during his post-doc, influenced PR transcriptional activity. In establishing his own lab, Tetel integrated his previous experience to apply cellular and molecular approaches to study the function of nuclear receptor coactivators in the regulation of hormone-dependent and -independent behavior and gene expression in brain. 

The Tetel lab was one of the first to show that steroid receptor coactivators are critical for efficient estrogen receptor (ER)-mediated transactivation of the PR gene in brain and in ER- and PR-dependent aspects female reproductive behavior. Tetel’s team has taken a proteomics-based approach to study how coactivators function with steroid receptors in hormone action in brain and behavior. In addition, they have collaborated with other labs to study the role of coactivators in a variety of other neuroendocrine functions and model systems. To better understand the mechanisms of hormone-dependent and -independent action in brain and behavior, it is essential to understand the function of nuclear receptor coactivators in these processes. The Tetel lab has been at the forefront of studying the role of these important coactivators of steroid receptors in hormone action in brain and behavior. More recently they have studied how estrogens regulate energy homeostasis in females. They were the first to show that neurogenesis occurs in the hypothalamus of adult female mice. Moreover, many of these new hypothalamic neurons are leptin-sensitive and are regulated by estradiol and high fat diet. They have expanded this work to include on-going investigations of the effects of estrogens and diet on the gut microbiota in female wild-type and ob/ob mice. Recently, they have extended this work to explore the effects of estrogens, diet, and microbiota in anxiety in female mice. Finally, in collaboration with colleagues at Mayo Clinic, the Tetel lab has been studying the effects of diet, exercise, and mood on the vaginal microbiome in women.
 

Tracy Bale’s research is centered on understanding the role of stress dysregulation in disease and the sex differences that underlie disease vulnerability. Her research team has developed mouse models relevant to neuropsychiatric diseases to study the interaction of genes and the environment, assessing epigenetic mechanisms involved in sex-specific programming of the brain and other tissues, and the transgenerational effects via germ cell reprogramming. To examine potential mechanisms, they have initiated multiple lines of investigation that will provide insight into the timing and sex specificity of early life events promoting disease susceptibility, the maturation of central pathways during key periods of development, and the epigenetic programming involved in long-term effects following stress experience. 

Bale has worked in preconception, prenatal, and pubertal programming and epigenetic mechanisms for over 15 years, with expertise in innovative molecular techniques such as ChIP-Seq and mass spectrometry to identify histone and miRNA targets, as well as stress physiology, sex differences, and behavioral expertise for over 20 years. 

In her role as a mentor, Bale has trained undergraduate and graduate students, postdocs, and fellows, many who were from underrepresented groups and the majority who were women. She assists students in formulating specific short and long-term goals and helps direct them to develop skills in hypothesis formulation, data interpretation, and scientific writing. Through her work as Director of the Center for Epigenetic Research in Child Health and Brain Development, Bale mentors trainees and junior faculty in study design and development, grant writing, and career development. Her role as President of the International Brain Research Organization allows her to mentor trainees around the globe in research, policy, travel and research grants, and career planning.