A5043591052- Pregnancy and preeclampsia studies
- Cytomegalovirus and herpesvirus research
- Sphingolipid Metabolism and Signaling
- Birth, Development, and Health
- Reproductive System and Pregnancy
- Gestational Diabetes Research and Management
- Nitric Oxide and Endothelin Effects
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Systemic Lupus Erythematosus Research
- Prenatal Screening and Diagnostics
- Erythrocyte Function and Pathophysiology
- Parvovirus B19 Infection Studies
- Inflammasome and immune disorders
- Maternal and fetal healthcare
- Toxoplasma gondii Research Studies
- Lipid Membrane Structure and Behavior
- Protein Kinase Regulation and GTPase Signaling
- Endoplasmic Reticulum Stress and Disease
- Herpesvirus Infections and Treatments
- Preterm Birth and Chorioamnionitis
- Eicosanoids and Hypertension Pharmacology
- T-cell and B-cell Immunology
- Diet, Metabolism, and Disease
- Hydrogen's biological and therapeutic effects
- Biomarkers in Disease Mechanisms
University of Alberta
2014-2024
Women and Children’s Health Research Institute
2015-2024
Alberta Hospital Edmonton
2024
The Maternal-Infant Research on Environmental Chemicals (MIREC) Study was established to obtain Canadian biomonitoring data for pregnant women and their infants, examine potential adverse health effects of prenatal exposure priority environmental chemicals pregnancy infant health.Women were recruited during the first trimester from 10 sites across Canada followed through delivery. Questionnaires administered post-delivery collect information demographics, occupation, life style, medical...
Compromised fetal growth impairs vascular function; however, it is unclear whether chronic hypoxia in utero affects adult endothelial function. We hypothesized that maternal (H, 12% O2, n= 9) or nutrient restriction (NR, 40% of control, 7) imposed from day 15-21 pregnancy rats would impair function male offspring (relative to C, 10). Using a wire myograph, endothelium-dependent relaxation response methacholine was assessed small mesenteric arteries 4- and 7-month-old (mo) offspring. Nitric...
Compared to normal tissues, many cancer cells overexpress autotaxin (ATX). This secreted enzyme produces extracellular lysophosphatidate, which signals through 6 GPCRs drive progression. Our previous work showed that ATX inhibition decreases 4T1 breast tumor growth in BALB/c mice by 60% for about 11 d. However, do not produce significant ATX. Instead, the is produced adjacent mammary adipose tissue. We investigated molecular basis of this interaction human and mouse tumors. Inflammatory...
ABSTRACT Forty percent of women with primary cytomegalovirus (CMV) infections during pregnancy infect their fetuses complications for the baby varying from mild to severe. How CMV crosses syncytiotrophoblast, barrier between maternal blood and fetal tissue in villous placenta, is unknown. Virus may cross by infection cells that pass through physical breaches syncytiotrophoblast or direct subsequent transmission underlying placental cells. In this study, we show pure (>99.99%), long-term...
Intrauterine growth restriction (IUGR) increases the risk of cardiovascular disease later in life. Vascular dysfunction occurs adult offspring from animal models IUGR including maternal undernutrition, but influence reduced fetal oxygen supply on vascular function is unclear. Myogenic responses, essential for tone regulation, have not been evaluated these offspring. We hypothesized that 7-mo-old hypoxic (12% O(2); H) or nutrient-restricted (40% control; NR) rat dams would show greater...
Tumor necrosis factor alpha (TNF alpha) induces the apoptotic death of primary villous cytotrophoblasts in culture (Yui et al., Placenta 1994; 15:819). Since both p55 and p75 TNF receptors (TNFRs) localize to trophoblast, we examined their roles mediating trophoblast apoptosis. Comparison 125I-TNF binding competition by receptor-specific antibodies revealed 2.7-fold more TNFRp75 than TNFRp55. Immunohistochemical analysis receptor distribution showed be expressed strongly < 20% cells TNFRp55...
We have previously established that adipose tissue adjacent to breast tumors becomes inflamed by tumor-derived cytokines. This stimulates autotaxin (ATX) secretion from adipocytes, whereas cancer cells produce insignificant ATX. Lysophosphatidate produced ATX promotes inflammatory cytokine in a vicious cycle, which increases tumor growth and metastasis decreases response chemotherapy. hypothesized damage during radiotherapy for should promote lysophosphatidic acid (LPA) signaling further...
Whether cell-free human immunodeficiency virus type 1 (HIV-1) can productively infect placental trophoblasts (which in turn could transmit the into fetal circulation) is controversial but essential to know for evaluation of alternative routes (such as cell-mediated infection or trophoblast damage). We have addressed factors such cell purity, source, culture methods, and activation states well variant detection methods conclusively determine outcome challenge by free virus. Pure (> 99.98%)...
Sphingosine 1‐phosphate (S1P), a bioactive lipid, signals through cell surface receptors to induce vasoconstriction and activate endothelial nitric oxide synthase (eNOS), suggesting role for S1P in vascular tone modulation. Using model of aging female rats, we investigated the vasoactivity roles eNOS estrogen replacement modulation that vasoactivity. Mesenteric arteries from aged rats were significantly more sensitive S1P‐induced than young reached greater maximum constriction (58.2±2.98 vs...
Cytomegalovirus (CMV) infects 40⁻70% of women, but infection has been reported in >95% breast cancer patients. We investigated the consequences these observations by infecting mice with mCMV or a negative control medium for 4 days, 11 days 10 weeks to establish active, intermediate latent infections, respectively. Syngeneic 4T1 E0771 cells were then injected into mammary fat pad BALB/c C57BL/6 mice, Infection did not affect tumor growth conditions, latently infected developed more lung...
Metastasis remains a major challenge in treating breast cancer. Breast tumors metastasize to organ-specific locations such as the brain, lungs, and bone, but why some organs are favored over others unclear. also show heterogeneity, plasticity, distinct microenvironments. This contributes treatment failure relapse. The interaction of cancer cells with their metastatic microenvironment has led concept that primary act seeds, whereas tissue (TME) is soil. Improving our understanding this could...
Sphingosine-1-phosphate (S1P), a bioactive lipid released from activated platelets, has been demonstrated in animal models to regulate vascular tone through receptor-mediated activation of Rho-associated kinase 1 and nitric oxide synthase 3. The role S1P regulation human (particularly during pregnancy, with its unique adaptations localized platelet activation) is unknown. We hypothesized that would constrict small placental arteries kinases modulation by oxide. Reverse...
Recruitment is a challenge in developing population-representative pregnancy and birth cohorts. We developed collaborative recruitment infrastructure (CRI) to recruit pregnant women for 4 cohorts using: faxes from obstetrical offices, in-clinic recruiters, university funder-driven free-media events, paid-media, attendance at relevant tradeshows. rates demographic differences were compared between methods. received 5008 referrals over 40 months. Compared fax, 13 times more likely be recruited...
Preeclampsia (PE) involves inadequate placental function. This can occur due to elevated pro-inflammatory tumor necrosis factor-α (TNF-α). In other tissues, TNF-α signals via sphingosine kinase 1 (SphK1). SphK1 hinders syncytial formation. Whether this occurs downstream of signaling is unclear. We hypothesized that levels are higher in PE and decreases function, increases shedding, cytokine/factor release activity. Term biopsies were analyzed for using immunofluorescence qRT-PCR. explants...
An appropriate balance between uterine quiescence and activation during pregnancy is essential for a successful outcome. Sphingosine 1-phosphate (S1P), bioactive lipid, increases cell survival, proliferation, angiogenesis, all important to maintain the pregnancy. Indeed progesterone sphingosine kinase 1 (SPHK1) mRNA, which produces S1P. In contrast, induction of prostaglandin endoperoxide synthase 2 by S1P stimulation SPHK1 estradiol cytokines suggests role in termination Human decidua...
Maternal carbohydrate intake is one important determinant of fetal body composition, but whether increased exposure to individual sugars has long-term adverse effects on the offspring not well established. Therefore, we examined effect fructose feeding mother, placenta, fetus and her up 6 months life when they had been weaned onto a standard rodent diet exposed additional fructose. Dams fed were fatter, raised plasma insulin triglycerides from mid-gestation higher glucose near term....
Human cytomegalovirus (HCMV) infects 40-70% of adults in developed countries. Detection HCMV DNA and/or proteins breast tumors varies considerably, ranging from 0-100%. In this study, nested PCR to detect glycoprotein B (gB) was shown be sensitive and specific contrast the detection for immediate early genes. gB detected 18.4% 136 while 62.8% 94 cancer patients were seropositive HCMV. mRNA gene not any sample, suggesting viral latency tumors. seropositivity positively correlated with age,...
Human cytomegalovirus (HCMV) is associated with vascular diseases in both immunosuppressed and immunocompetent individuals. CMV infections cycle between active latent phases throughout life. We others have shown dysfunction during mouse (mCMV) infections. Few studies examined changes physiology infections, particularly responses or whether the negative effects of aging on function fertility will be exacerbated under these conditions. measured intact mesenteric uterine arteries dissected from...