Tissue stem cell lineages sense and respond to the external and systemic environments. Our lab investigates the physiological, cellular and molecular in vivo mechanisms involved in this complex process using the powerful Drosophila oogenesis model. Over the past 20 years, we have made major discoveries shedding light on a multi-organ network that tightly coordinates the germline stem cell lineage with whole-body physiology and diet.
Control of stem cell lineages by diet, physiology, and metabolism
Tissue stem cell lineages maintain organ function and respond to dietary and physiological factors, and they also experience intrinsic metabolic shifts as cells differentiate. Metabolic and physiological alterations are also linked to multiple diseases, including obesity and cancer. The mechanisms associated with intrinsic metabolic shifts in stem cell lineages and how physiological factors affect them remain underexplored. We investigate these mechanisms using a powerful genetic model organism, Drosophila melanogaster, which has a fascinating biology and strong history of broadly relevant fundamental discoveries. Egg production in Drosophila is maintained by stem cell populations through energy/resource-intensive processes that are highly coordinated with nutrient availability and organismal physiology.
Over the past 20 years, our work has shed light on the complex network linking stem cells and oogenesis to whole-body physiology. For example, we showed that: germline stem cells and their progeny grow and divide faster on nutrient-rich rather than poor diets; insulin, Target of Rapamycin, AMP kinase, and a steroid hormone regulate specific steps in the germ cell lineage; adipocytes control germline stem cells and their progeny downstream of amino acid sensing and metabolic changes; nuclear receptors in adipocytes, hepatocyte-like cells, and muscles regulate factors involved in inter-organ communication with the ovary.
We are interested in several questions: 1) How do specific dietary changes affect the germline stem cell lineage? How are physiology and metabolism integrated in the germline stem cell lineage? How does obesity affect stem cell lineages and reproduction? This research provides fundamental new knowledge to significantly advance our understanding of the integration between metabolism and physiology in the control of stem cell lineages and reproduction in vivo, with the potential to inform future research additional stem cell systems and how their metabolic deregulation is tied to diseased states.
Effects of temperature on reproduction
According to the United Nations, “climate change is the defining crisis of our time and it is happening even more quickly than we feared.” As temperatures steadily rise on Earth due to human activity-derived CO2 release, we experience more natural disasters, weather extremes, environmental degradation, and negative economic impact.
Our lab is interested in understanding how temperature impacts the reproduction of organisms. Insects have a limited capacity to regulate their temperature and are particularly sensitive to environmental temperature. Insects are medically, economically, and ecologically relevant; they are the most diverse group of animals and include disease vectors, agricultural pests, pollinators, and protein sources. We recently showed that chronic exposure to cool temperature improves germline stem cell maintenance, the survival of differentiating germ cells, and the quality of oocytes produced, while warm temperature increases germ cell death and follicle degeneration and impairs oocyte quality.
Our current research addresses the mechanisms underlying the effects of temperature on Drosophila oogenesis, with the potential to generate valuable insights into how rising environmental temperatures affect insect reproduction more broadly, and into how fevers or heatstroke might impact fertility in mammals.