A5065455714- Pregnancy and preeclampsia studies
- Birth, Development, and Health
- High Altitude and Hypoxia
- Gestational Diabetes Research and Management
- Neuroscience of respiration and sleep
- Cancer, Hypoxia, and Metabolism
- Adipose Tissue and Metabolism
- Neonatal Respiratory Health Research
- Heme Oxygenase-1 and Carbon Monoxide
- Epigenetics and DNA Methylation
- Traumatic Brain Injury and Neurovascular Disturbances
- Heart Rate Variability and Autonomic Control
- Cardiovascular Issues in Pregnancy
- Cardiovascular and Diving-Related Complications
- Mitochondrial Function and Pathology
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Peroxisome Proliferator-Activated Receptors
- Nitric Oxide and Endothelin Effects
- Congenital Diaphragmatic Hernia Studies
- Cardiovascular Health and Disease Prevention
- Global Maternal and Child Health
- Congenital heart defects research
- Sphingolipid Metabolism and Signaling
- Metabolism, Diabetes, and Cancer
- Health, Environment, Cognitive Aging
University of Colorado Denver
2016-2025
University of Colorado Anschutz Medical Campus
2014-2025
Xiangya Hospital Central South University
2016
Central South University
2016
University of Turku
2016
University of Oregon
2016
High Altitude Observatory
2008-2015
University of Colorado Boulder
2015
Women and Children’s Health Research Institute
2015
University of Alberta
2015
High-altitude hypoxia (reduced inspired oxygen tension due to decreased barometric pressure) exerts severe physiological stress on the human body. Two high-altitude regions where humans have lived for millennia are Andean Altiplano and Tibetan Plateau. Populations living in these exhibit unique circulatory, respiratory, hematological adaptations life at high altitude. Although responses been well characterized physiologically, their underlying genetic basis remains unknown. We performed a...
Abstract Sphingosine-1-phosphate (S1P) is a bioactive signalling lipid highly enriched in mature erythrocytes, with unknown functions pertaining to erythrocyte physiology. Here by employing nonbiased high-throughput metabolomic profiling, we show that S1P levels rapidly increase 21 healthy lowland volunteers at 5,260 m altitude on day 1 and continue increasing 16 days concurrently elevated sphingonisne kinase (Sphk1) activity haemoglobin (Hb) oxygen (O 2 ) release capacity. Mouse genetic...
High-altitude environments (>2,500 m) provide scientists with a natural laboratory to study the physiological and genetic effects of low ambient oxygen tension on human populations. One approach understanding how life at high altitude has affected metabolism is survey genome-wide datasets for signatures selection. In this work, we report identify selection-nominated candidate genes involved in adaptation hypoxia one highland group, Andeans from South American Altiplano. We analysed dense...
Background: High altitude is a challenging condition caused by insufficient oxygen supply. Inability to adjust hypoxia may lead pulmonary edema, stroke, cardiovascular dysfunction, and even death. Thus, understanding the molecular basis of adaptation high reveal novel therapeutics counteract detrimental consequences hypoxia. Methods: Using high-throughput, unbiased metabolomic profiling, we report that metabolic pathway responsible for production erythrocyte 2,3-bisphosphoglycerate...
Objectives High‐altitude hypoxia, or decreased oxygen levels caused by low barometric pressure, challenges the ability of humans to live and reproduce. Despite these challenges, human populations have lived on Andean Altiplano Tibetan Plateau for millennia exhibit unique circulatory, respiratory, hematological adaptations life at high altitude. We others identified natural selection candidate genes gene regions using dense genome scan data. One previously known be important in cellular...
Evolutionary trade-offs required for bipedalism and brain expansion influence the pregnancy rise in uterine artery (UtA) blood flow and, turn, reproductive success. We consider importance of UtA by reviewing its determinants presenting data from 191 normotensive (normal, n = 125) or hypertensive (preeclampsia (PE) gestational hypertension (GH), 29) Andean residents very high (4100–4300 m) low altitude (400 m, 37). Prior studies show that is reduced pregnancies with intrauterine growth...
Red blood cells (RBCs) are key players in systemic oxygen transport. RBCs respond to vitro hypoxia through the so-called oxygen-dependent metabolic regulation, which involves competitive binding of deoxyhemoglobin and glycolytic enzymes N-terminal cytosolic domain band 3. This mechanism promotes accumulation 2,3-DPG, stabilizing deoxygenated state hemoglobin, cytosol acidification, triggering off-loading Bohr effect. Despite studies, vivo adaptations have not yet been completely elucidated....
Low birth weight and intrauterine growth restriction (IUGR) increase the risk of mortality morbidity during perinatal period as well in adulthood. Environmental genetic factors contribute to IUGR, but influence maternal variation on is largely unknown. We implemented a gene-by-environment study wherein we utilized restrictive effects high altitude. Multigenerational high-altitude residents (Andeans) are protected from altitude-associated IUGR compared with recent migrants (Europeans). Using...
An understanding of human responses to hypoxia is important for the health millions people worldwide who visit, live, or work in hypoxic environment encountered at high altitudes. In spite dozens studies over last 100 years, basic mechanisms controlling acclimatization remain largely unknown. The AltitudeOmics project aimed bridge this gap. Our goals were 1) describe a phenotype successful and assess its retention 2) use these findings as foundation companion mechanistic studies. approach...
Lactate is a ubiquitous molecule in cancer. In this exploratory study, our aim was to test the hypothesis that lactate could function as an oncometabolite by evaluating whether exposure modifies expression of oncogenes, or genes encoding transcription factors, cell division and proliferation MCF7 cells, human breast cancer line. Gene compared between cells incubated (a) glucose/glutamine-free media (control), (b) glucose-containing stimulate endogenous production (replicating some original...
This study was designed to test the hypothesis that intermittent normobaric hypoxia at rest is a sufficient stimulus elicit changes in physiological measures associated with improved performance highly trained distance runners. Fourteen national-class runners completed 4-wk regimen (5:5-min hypoxia-to-normoxia ratio for 70 min, 5 times/wk) of (Hyp) or placebo control (Norm) rest. The experimental group exposed graded decline fraction inspired O2: 0.12 (week 1), 0.11 2), and 0.10 (weeks 3 4)....
We studied 22 twin pairs in which one or both twins had dementia of the Alzheimer type (DAT). In four twins, diagnosis was confirmed by autopsy. Seven monozygotic (MZ) were concordant for DAT; 10 MZ discordant. Two dizygotic (DZ) DAT, and 3 DZ The current concordance rate 41% 40% twins. study supports belief that, etiologically, DAT cannot be entirely accounted a single autosomal dominant gene. data also suggest that certain genetic circumstances, disease expression may delayed females.
The effect of high altitude on reducing birth weight is markedly less in populations high- (e.g., Andeans) relative to low-altitude origin Europeans). Uterine artery (UA) blood flow greater during pregnancy Andeans than Europeans at altitude; however, it not clear whether such differences play a causal role ancestry-associated variations fetal growth. We tested the hypothesis that UA contributes protection growth afforded by Andean ancestry comparing and throughout 137 or European residents...
The chronic hypoxia of high-altitude (>/=2500 m) residence has been shown to decrease birth weight in all populations studied date. However, multigenerational appear protected relative newcomer groups. This study aimed determine whether such protection exists independently other factors known influence fetal growth and admixed (ie, people having both high- low-altitude ancestry) show an intermediate level protection.3551 medical records from consecutive deliveries Andean, European or Mestizo...
Reduced uteroplacental blood flow is hypothesized to play a key role in altitude-associated fetal growth restriction. It unknown whether reduced cause or consequence of size. We asked determinants were altered prior and vasoactive and/or angiogenic factors involved. Women residing at low (LA; 1,600 m, n = 18) high altitude (HA; 3,100 25) studied during pregnancy (20, 30, 36 wk) 4 mo postpartum (PP) using Doppler ultrasound. In each study, endothelin (ET-1), nitric oxide metabolites (NO(x)),...
The pathophysiology of acute mountain sickness (AMS) is unknown. One hypothesis that hypoxia induces biochemical changes disrupt the blood-brain barrier (BBB) and, subsequently, lead to development cerebral edema and defining symptoms AMS. This study explores relationship between AMS biomarkers thought protect against or contribute BBB disruption. Twenty healthy volunteers participated in a series hypobaric trials distinguished by pretreatment with placebo, acetazolamide (250 mg),...
It is classically thought that increases in hemoglobin mass (Hbmass) take several weeks to develop upon ascent high altitude and are lost gradually following descent. However, the early time course of these erythropoietic adaptations has not been thoroughly investigated data lacking at elevations greater than 5000 m, where hypoxic stimulus dramatically increased. As part AltitudeOmics project, we examined Hbmass healthy men women sea level (SL) 5260 m 1, 7, 16 days exposure...
Abstract Faster acclimatization to high altitude upon re-ascent is seen in humans; however, the molecular basis for this enhanced adaptive response unknown. We report that healthy lowlanders, plasma adenosine levels are rapidly induced by initial ascent and achieved even higher re-ascent, a feature positively associated with quicker acclimatization. Erythrocyte equilibrative nucleoside transporter 1 (eENT1) reduced humans at mice under hypoxia. eENT1 deletion allows rapid accumulation of...
Multigenerational (Andean) compared with shorter-term (European) high-altitude residents exhibit less hypoxia-associated reductions in birth weight. Because differences arterial O 2 content are not responsible, we asked whether greater pregnancy-associated increases uterine artery (UA) blood flow and delivery were involved. Serial studies conducted 42 Andean 26 European of La Paz, Bolivia (3600 m) at weeks 20, 30, 36 pregnancy 4 mo postpartum using Doppler ultrasound. There no but vs. women...