A5065844344- Mitochondrial Function and Pathology
- Metabolism and Genetic Disorders
- ATP Synthase and ATPases Research
- Adipose Tissue and Metabolism
- RNA modifications and cancer
- MicroRNA in disease regulation
- Autophagy in Disease and Therapy
- Cancer-related molecular mechanisms research
- Diamond and Carbon-based Materials Research
- Birth, Development, and Health
- Infant Nutrition and Health
- Cancer, Hypoxia, and Metabolism
- Cell death mechanisms and regulation
- Chemotherapy-induced cardiotoxicity and mitigation
- Gestational Diabetes Research and Management
- Adenosine and Purinergic Signaling
- Neonatal Respiratory Health Research
- Clinical Nutrition and Gastroenterology
- RNA Research and Splicing
- Endoplasmic Reticulum Stress and Disease
- Electron Spin Resonance Studies
- Carbon Nanotubes in Composites
- Histone Deacetylase Inhibitors Research
- Metabolism, Diabetes, and Cancer
- Calpain Protease Function and Regulation
University of Manitoba
2011-2022
Children's Hospital Research Institute of Manitoba
2015-2022
Manitoba Beekeepers' Association
2014
St. Boniface Hospital
2011-2012
Abstract Exposure to metabolic disease during fetal development alters cellular differentiation and perturbs homeostasis, but the underlying molecular regulators of this phenomenon in muscle cells are not completely understood. To address this, we undertook a computational approach identify cooperating partners myocyte enhancer factor-2 (MEF2) family transcription factors, known function. We demonstrate that MEF2 serum response factor (SRF) collaboratively regulate expression numerous...
Myocardin is a transcriptional co-activator required for cardiovascular development, but also promotes cardiomyocyte survival through an unclear molecular mechanism. Mitochondrial permeability transition implicated in necrosis, while pore closure mitochondrial maturation during cardiac development. We show that loss of myocardin function leads to subendocardial necrosis at E9.5, concurrent with elevated expression the death gene Nix. Mechanistically, we demonstrate knockdown reduces...
The cellular response to hypoxia involves the activation of a conserved pathway for gene expression regulated by transcription factor complex called hypoxia-inducible (HIF). This has been implicated in both adaptive and several hypoxic-ischemic-related pathologies. Perinatal hypoxic injury, often associated with prematurity, leads multi-organ dysfunction resulting significant morbidity mortality. Using rodent model neonatal representative cell lines, we observed HIF1α down-stream induction...
The aim of the present study was to determine in vitro effect(s) a bovine-based human breast milk fortifier (HMF) on intestinal cells. HMF increases expression BCL2/adenovirus E1B 19 kDa protein-interacting protein (Bnip3) and cell death; prostaglandin analogue misoprostol will rescue this effect.Cultured cells were exposed vitro-digested (BM) ± HMF. Intracellular oxidation, damage/cell death, BNIP3 measured after exposure.In BM + significantly increased intracellular damage, death...
Abstract The cellular response to hypoxia involves the activation of a conserved pathway for gene expression regulated by transcription factor complex called hypoxia-inducible (HIF). This has been implicated in both adaptive and several hypoxic-ischemic related pathologies. Perinatal hypoxic injury, often associated with prematurity, leads multi-organ dysfunction resulting significant morbidity mortality. Using rodent model neonatal representative cell lines, we observed HIF1α down-stream...
Fetal exposure to diabetes during pregnancy increases the risk for early‐onset insulin resistance in offspring; however, key molecular regulators responsible fetal metabolic programming have not been characterized muscle tissue. We demonstrate that prenatal gestational decreased soleus expression of microRNA‐133a offspring. Using tandem mass spectrometry techniques we identify a conserved phosphorylation motif within MEF2 and SRF transcription factors is targeted by PKCδ regulates...
Necrotizing enterocolitis is the most common gastrointestinal emergency affecting low‐birth weight premature infants, with an incidence between 3% and 10% in infants less than 1500 grams, mortality ranging from 15% to 30%. The pathogenesis of NEC not clearly defined, but likely a multifactorial disease wherein intestinal ischemia hypoxia play fundamental roles. hypoxia‐inducible death gene Bnip3 has been recently identified as key regulator NEC, yet molecular mechanisms surrounding...
Myocardin is a transcriptional co‐activator required for cardiovascular development and cardiomyocyte differentiation. Recent studies have shown that genetic inhibition of myocardin results in congenital heart defects associated with increased programmed cell death (PCD). In addition to its established role regulating PCD, the mitochondrial permeability transition pore (PTP) has been implicated cardiac calcium homeostasis myocyte maturation during development. Utilizing fluorescent staining...
Neonatal hypoxia affects more than 50% of preterm infants and is implicated in a number diseases prematurity. The exact mechanism for hypoxic injury remains unclear, although it appears that the genetically conserved, pro‐death Bnip3 pathway may play central role. Previous work has suggested transcription factor known as NF‐kB bind to promoter region repress its expression, thereby preventing induction cell death. Additionally, our laboratory shown misoprostol, prostaglandin E2 receptor...
Bnip3 is a hypoxia‐regulated gene that has been reported to promote either cell death or survival depending on the cellular context. The transcription factor NF‐κB previously shown repress expression survival. However, more recent data suggests subjected alternative splicing produce pro‐death and pro‐survival isoforms, suggesting molecular mechanism for regulating balance between in hypoxic cells. Mitochondrial matrix calcium accumulation implicated regulated necrotic death, while nuclear...
Myocardin is a transcriptional co‐activator required for cardiovascular development and cardiomyocyte differentiation. Recent studies have shown that genetic inhibition of myocardin results in embryonic lethality with impaired proliferation increased programmed cell death. Mitochondrial permeability transition, triggered by matrix calcium accumulation, has been implicated regulated necrotic death, while transition pore closure involved myocyte differentiation mitochondrial maturation during...
Bnip3 is a hypoxia-inducible initiator of cardiomyocyte cell death and has also been implicated as mitochondrial receptor for the cellular mitophagy machinery. Previous work from our group demonstrates that prostaglandin E1 analogue, misoprostol, prevents hypoxia-induced dysfunction potent activator PKA. We hypothesize misoprostol alters phosphorylation status Bnip3, inhibiting its ability to induce mitophagy, death. Using rodent model neonatal hypoxia, in combination with rat primary...
Abstract Doxorubicin (DOX) is an effective anthracycline used in chemotherapeutic regimens for a variety of haematological and solid tumors. However, its utility remains limited by well-described, but poorly understood cardiotoxicity. Despite numerous studies describing various forms regulated cell death their involvement DOX-mediated cardiotoxicity, the predominate form unclear. Part this inconsistency lies lack standardization vivo vitro model design. To end, objective study was to...