A5055595385- Neurobiology and Insect Physiology Research
- Invertebrate Immune Response Mechanisms
- Sexual Differentiation and Disorders
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Insect symbiosis and bacterial influences
- Genetics, Aging, and Longevity in Model Organisms
- Insect and Arachnid Ecology and Behavior
- Pancreatic function and diabetes
- Ubiquitin and proteasome pathways
- Physiological and biochemical adaptations
- Hormonal Regulation and Hypertension
- Sperm and Testicular Function
- Metabolism, Diabetes, and Cancer
- Parallel Computing and Optimization Techniques
- Insect Utilization and Effects
- Signaling Pathways in Disease
- Vibrio bacteria research studies
- Hyperglycemia and glycemic control in critically ill and hospitalized patients
- Protein Degradation and Inhibitors
- Estrogen and related hormone effects
- Insect and Pesticide Research
- Adipose Tissue and Metabolism
- FOXO transcription factor regulation
- Lipid metabolism and disorders
University of Virginia
2016-2024
University of Pennsylvania
2010-2011
Institute of Nutrition, Metabolism and Diabetes
2009
University of California, San Francisco
2000-2004
National Institute of Neurological Disorders and Stroke
2000
National Institutes of Health
2000
Innate immunity is the primary and most ancient defense against infection. Although critical to survival, coordinating protection a foreign organism energetically costly, creating need reallocate substrates from nonessential functions, such as growth nutrient storage. However, mechanism by which infection or inflammation leads reduction in energy utilization these dispensable processes not well understood. Here, we demonstrate that activation of Toll signaling pathway selectively fat body,...
Adrenal steroids are essential for homeostasis and survival during severe physiological stress. Analysis of a patient heterozygous the steroidogenic factor-1 (SF-1) gene suggested that reduced expression this nuclear receptor leads to adrenal failure. We therefore examined SF-1 (+/-) mice as potential model delineating mechanisms underlying disease. Here we show +/- exhibit insufficiency resulting from profound defects in development organization. However, compensatory mechanisms, such...
During infection, cellular resources are allocated toward the metabolically-demanding processes of synthesizing and secreting effector proteins that neutralize kill invading pathogens. In Drosophila , these effectors antimicrobial peptides (AMPs) produced in fat body, an organ also serves as a major lipid storage depot. Here we asked how activation Toll signaling larval body perturbs homeostasis to understand cells meet metabolic demands immune response. We find genetic or physiological...
The importance of steroidogenic factor-1 (SF-1) gene dosage in endocrine function is evidenced by phenotypes associated with the heterozygous state mice and humans. Here we examined mechanisms underlying SF-1 haploinsufficiency found a striking reduction (12-fold) (+/−) adrenocortical size at embryonic day (E) 12. Loss one allele led to selective decrease adrenal precursors within adrenogonadal primordium E10.0, without affecting number gonadal precursors, as marked GATA-4. Beginning E13.5,...
Chronic enteropathogen infection in early childhood reduces circulating insulin-like growth factor 1 (IGF1) levels and restricts growth. Pathogen-derived molecules activate host Toll-like receptors to initiate the immune response, but whether this pathway contributes inhibition is unclear. In Drosophila, activation of Toll larval fat body suppresses whole-animal Here, using a transcriptomic approach, we identify Drosophila peptide 6 (Dilp6), fat-body-derived IGF1 ortholog, as selective...
In obese adipose tissue, Toll-like receptor signaling in macrophages leads to insulin resistance adipocytes. Similarly, Toll the Drosophila larval fat body blocks insulin-dependent growth and nutrient storage. We find that acts cell autonomously block but not PI(3,4,5)P3 production cells expressing constitutively active PI3K. Fat whole-animal rictor mutants lacking TORC2 activity, larvae Pdk1. Phosphorylation of Akt on Pdk1 site, Thr342, is significantly reduced by signaling, expression...
Abstract Stress hyperglycemia and insulin resistance are evolutionarily conserved metabolic adaptations to severe injury including major trauma, burns, or hemorrhagic shock (HS). In response injury, the neuroendocrine system increases secretion of counterregulatory hormones that promote rapid mobilization nutrient stores, impair action, ultimately cause hyperglycemia, a condition known recovery from in clinical setting. We investigated contributions adipocyte lipolysis acute stress. Both...
Dietary nutrients provide macromolecules necessary for organism growth and development. In response to animal feeding, evolutionarily conserved signaling pathways are activated, leading increased rates of cell proliferation tissue growth. It remains unclear how different types within developing tissues coordinate in dietary whether coordinated is proper function. Using the early Drosophila larval brain, we asked nutrient-dependent neural stem cells (neuroblasts), glia, trachea among these...
ABSTRACT Nutrient intake is obligatory for animal growth and development, but nutrients alone are not sufficient. Indeed, insulin homologous hormones required normal even in the presence of nutrients. These communicate nutrient status between organs, allowing animals to coordinate metabolism with supply. Insulin related hormones, such as insulin-like factors peptides, play important roles development metabolism, defects production signaling leading hyperglycemia diabetes. Here, we describe...
Abstract During infection, cellular resources are allocated toward the metabolically-demanding processes of synthesizing and secreting effector proteins that neutralize kill invading pathogens. In Drosophila , these effectors antimicrobial peptides (AMPs) produced in fat body, an organ also serves as a major lipid storage depot. Here we asked how activation Toll signaling larval body perturbs homeostasis to understand cells meet metabolic demands immune response. We find genetic leads...
The power of Drosophila genetics is increasingly being applied to questions hormone signaling and metabolism the development models human disease in this organism. Sensitive methods for measurements parameters such as metabolic rates are needed drive understanding physiology small animals fruit fly. method described here assesses fuel oxidation numbers adult flies fed food containing trace amounts 14C-labeled substrates glucose or fatty acid. After feeding period any additional experimental...
"Gene Dosage Effects of Steroidogenic Factor 1 (SF-1) in Adrenal Development and the Stress." Endocrine Research, 26(4), pp. 515–516
The power of Drosophila genetics is increasingly being applied to questions hormone signaling and metabolism the development models human disease in this organism. Sensitive methods for measurements parameters such as metabolic rates are needed drive understanding physiology small animals fruit fly. method described here assesses fuel oxidation numbers adult flies fed food containing trace amounts 14C-labeled substrates glucose or fatty acid. After feeding period any additional experimental...
ABSTRACT Nutrient intake drives secretion of insulin and insulin-like peptides that stimulate glucose uptake, nutrient storage, protein synthesis cell growth. The Drosophila genome encodes seven (Dilps) bind to a single known receptor drive growth storage. Whether Dilps respond uniformly changes in dietary nutrients is unknown. Here we characterized the endocrine response starvation sugar mid-third instar larvae, measuring circulating Dilp2, derived from insulin-producing cells brain, Dilp6,...