About the Coss Lab
The Coss Lab's research goal is to understand how the endocrine cell integrates the panoply of neuroendocrine and peripheral hormonal signals, in addition to metabolic cues and environmental insults, to result in the precise rhythm of synthesis and a delicate balance of hormones that regulate homeostasis.
In particular, the lab is interested to elucidate the regulation of reproductive function and studies the hormones of the hypothalamic-pituitary-gonadal axis and their cross talk with metabolic or inflammatory pathways in regulation of fertility. We aim to uncover fundamental processes controlling pubertal development, reproductive cyclicity in the female, and steroidogenesis and gametogenesis, to better understand disorders that lead to infertility, such as premature ovarian failure and polycystic ovarian syndrome (PCOS), that may lead us to identify prevention and treatment strategies.
We use a variety of in vitro and ex vivo approaches in cell lines and primary cells with integrative genome-wide, biochemical and cell and molecular biology methodologies to understand the regulation of reproductive fitness at the molecular level; and in vivo mouse models, knockouts and wildtypes, at the whole animal level to define the strategies used by the endocrine system to regulate the physiology of the organism.
Djurdjica Coss, Ph.D.
Associate Professor of Biomedical Sciences
Office: (951) 827-7791
Lab: (951) 827-7798
Office: 303 School of Medicine Research Building
Laboratory: 310 Research Lab 1; SOM Research Building
Energy Homeostasis and Weight Balance in Reproductive Fitness
Energy homeostasis and weight balance are critical components of reproductive fitness. Both extremes of women's weight are not conducive for maintenance of reproductive health and metabolic indicators impinge on the HPG on both hypothalamic and pituitary level. This research will provide important and particular relevance to the growing epidemic of obesity in the U.S and western world. With each yearly increase in the number of women of child-bearing age in the U.S. that are over-weight, obesity has become one of the greatest concerns in women’s health for those who plan to become pregnant or are pregnant. Since perturbation of hormone levels in mothers during pregnancy has far-reaching consequences that affect the adult physiology of the progeny, the results from the Coss lab research may also reveal new areas of research into the prenatal origins of adult reproductive disorders. To understand the impact of energy balance and hyperinsulinimia on reproductive health, we analyze whole animals physiology using mice on specific diets and conditional knock-outs, to investigate changes in gene expression and hormone secretion, as well as prenatal and pubertal development of the HPG axis.
How Inflammatory Pathways Influence Gonadotropin-Releasing Hormones (GnHR)
The brain controls the reproductive physiology through neurohormones secreted from hypothalamic neurons. In particular, at the apex of the HPG axis is gonadotropin-releasing hormone (GnRH). GnRH on the other hand is influenced or interacts with other neurohormones to influence pituitary gonadotrope function. GnRH neuron is regulated not only at the level of gene expression but at the level of pulsatility, since pulse frequency modulation is necessary to reproductive fitness. Using transgenic animals we are identifying the factors that contribute to GnRH gene expression and pulse generation. Specifically, we are interested how inflammatory pathways influence GnRH expression and secretion.
We use gonadotrope cells as a model to understand how endocrine cells integrates neuroendocrine signals, gonadal feedback, environmental, endocrine and paracrine influences to specifically, but differentially, synthesize two different hormones that are crucial for reproductive fitness. We aim to identify signaling mechanisms that differentially regulate the synthesis of two gonadotropin hormones, luteinizing hormone and follicle-stimulating hormone that control steroidogenesis and gametogenesis and aid in overcoming infertility problems as well as in developing novel contraceptive approaches. Using genome-wide and proteomics approaches, we are currently identifying co-regulated genes, interacting factors, co-activators and chromatin modulating enzymes that form on gonadotropin promoters to regulate the differential expression of gonadotropin hormones at the level of the gonadotrope transcriptome.