Shelley Harris
A5060409191- Aldose Reductase and Taurine
- Birth, Development, and Health
- Pregnancy and preeclampsia studies
- Pancreatic function and diabetes
- Renal Diseases and Glomerulopathies
- Neonatal Health and Biochemistry
- Hormonal Regulation and Hypertension
- Prenatal Screening and Diagnostics
- Adipose Tissue and Metabolism
- Cell Image Analysis Techniques
- Single-cell and spatial transcriptomics
- Liver Disease Diagnosis and Treatment
- Diet, Metabolism, and Disease
- Nuclear Receptors and Signaling
- Neonatal Respiratory Health Research
- RNA and protein synthesis mechanisms
- Hyperglycemia and glycemic control in critically ill and hospitalized patients
- Congenital Heart Disease Studies
- Diet and metabolism studies
- Chronic Kidney Disease and Diabetes
- Chronic Lymphocytic Leukemia Research
- CRISPR and Genetic Engineering
- Thyroid Disorders and Treatments
- Congenital heart defects research
- Cancer Genomics and Diagnostics
University of Southampton
2020-2024
Manchester University NHS Foundation Trust
2013-2024
Manchester Royal Infirmary
2006-2024
Oxford Centre for Diabetes, Endocrinology and Metabolism
2020-2022
Churchill Hospital
2020-2022
University of Oxford
2017-2022
Faculty (United Kingdom)
2022
IIT@MIT
2021
McGovern Institute for Brain Research
2021
Engineering Arts (United States)
2021
Identifying transcript location in cells where specific RNAs occur within a cell or tissue has been limited by technology and imaging capabilities. Expansion microscopy allowed for better visualization of small structures expanding the tissues with polymer- hydrogel-based system. Alon et al. combined expansion long-read situ RNA sequencing, resulting more precise transcripts. This method, termed “ExSeq” was used to detect RNAs, both new transcripts those previously demonstrated localize...
Abstract A holistic understanding of tissue and organ structure function requires the detection molecular constituents in their original three-dimensional (3D) context. Imaging mass cytometry (IMC) enables simultaneous up to 40 antigens transcripts using metal-tagged antibodies but has so far been restricted two-dimensional imaging. Here we report development 3D IMC for multiplexed analysis at single-cell resolution demonstrate utility technology by human breast cancer samples. The resulting...
The glomerular basement membrane (GBM) is a specialized extracellular matrix (ECM) compartment within the glomerulus that contains tissue-restricted isoforms of collagen IV and laminin. It integral to capillary wall therefore, functionally linked filtration. Although composition GBM has been investigated with global candidate-based approaches, relative contributions cell types production ECM are not well understood. To characterize specific cellular GBM, we used mass spectrometry–based...
Abstract Determining the genetic bases of age-related disease remains a major challenge requiring spectrum approaches from human and clinical genetics to utilization model organism studies. Here we report large-scale screen in mice employing phenotype-driven discovery platform identify mutations resulting disease, both late-onset progressive. We have utilized N -ethyl- -nitrosourea mutagenesis generate pedigrees mutagenized that were subject recurrent screens for mutant phenotypes as aged....
The heterogeneity of breast cancer plays a major role in drug response and resistance has been extensively characterized at the genomic level. Here, single-cell mass cytometry (BCMC) panel is optimized to identify cell phenotypes their oncogenic signalling states biobank patient-derived tumour xenograft (PDTX) models representing diversity human cancer. BCMC identifies 13 cellular (11 2 murine), associated with both subtypes specific features. Pre-treatment phenotypic composition determinant...
Abstract Congenital heart disease (CHD) is the most common class of human birth defects, with a prevalence 0.9% births. However, two-thirds cases have an unknown cause, and many these are thought to be caused by in utero exposure environmental teratogens. Here we identify potential teratogen causing CHD mice: maternal iron deficiency (ID). We show that ID mice causes severe cardiovascular defects offspring. These likely arise from increased retinoic acid signalling embryos. The can prevented...
The pathogenesis of nonalcoholic fatty liver disease (NAFLD) and the progression to steatohepatitis (NASH) increased risk hepatocellular carcinoma remain poorly understood. Additionally, there is increasing recognition extrahepatic manifestations associated with NAFLD NASH. We demonstrate that intervention American lifestyle-induced obesity syndrome (ALIOS) diet in male female mice recapitulates many clinical transcriptomic features human Male C57BL/6N were fed either normal chow (NC) or...
Despite having a single evolutionary origin and conserved function, the mammalian placenta exhibits radical structural diversity. The drivers functional consequences of placental diversity are poorly understood. Humans equids both display treelike villi, however these villi evolved independently exhibit starkly different levels invasiveness into maternal tissue (i.e. number layers between blood). in species therefore serve as compelling case study to explore whether placentas have developed...
Primary membranous nephropathy is associated with variable clinical course ranging from spontaneous remission to slow progression end stage renal failure. Achieving confers better survival in primary (PMN). Longer term outcomes such as patient and relapse of active disease remain poorly understood.We performed a retrospective study 128 consecutive adult patients diagnosed biopsy proven PMN at single UK centre between 1980 2010. These were followed prospectively over median months. We...
Introduction: Kidney transplantation is the preferred modality of kidney replacement therapy for eligible patients with end-stage disease (ESKD), given that it has been found to reduce mortality rates, improve quality life, and cost-effective compared dialysis. Recent advancements in human leukocyte antigen (HLA) typing donor-specific antibody (DSA) detection have helped risk rejection, but antibody-mediated rejection (AMR) can still occur without DSA. Previous studies suggest be attributed...
Thyroid hormones are important regulators of growth and maturation before birth, although the extent to which their actions mediated by insulin development pancreatic beta cell mass is unknown. Hypothyroidism in fetal sheep induced removal thyroid gland caused asymmetric organ growth, increased proliferation, was associated with circulating concentrations leptin. In isolated islets studied vitro, inhibited proliferation a dose-dependent manner, while high leptin stimulated proliferation. The...
Steroid 5β-reductase (AKR1D1) plays important role in hepatic bile acid synthesis and glucocorticoid clearance. Bile acids glucocorticoids are potent metabolic regulators, but whether AKR1D1 controls phenotype vivo is unknown. Akr1d1 –/– mice were generated on a C57BL/6 background. Liquid chromatography/mass spectrometry, metabolomic transcriptomic approaches used to determine effects homeostasis. Metabolic phenotypes including body weight composition, lipid homeostasis, glucose tolerance...
Pericytes are a common feature in the placental microvasculature but their roles not well understood. may provide physical or endocrine support for endothelium and some tissues mediate vasoconstriction. This study uses serial block-face scanning electron microscopy (SBFSEM) to generate three-dimensional (3D) reconstructions of pericytes terminal villi transmission (TEM) pericyte endothelial cell interactions. The proportion junctions covered by was determined. detailed 3D models show...
Non-alcoholic fatty liver disease (NAFLD) is the most common chronic condition. It tightly associated with an adverse metabolic phenotype (including obesity and type 2 diabetes) as well obstructive sleep apnoea (OSA) of which intermittent hypoxia a critical component. Hepatic de novo lipogenesis (DNL) significant contributor to hepatic lipid content pathogenesis NAFLD has been proposed key pathway target in development pharmacotherapies treat NAFLD. Our aim use experimental models...
Background: Development of adipose tissue before birth is essential for energy storage and thermoregulation in the neonate cardiometabolic health later life. Thyroid hormones are important regulators growth maturation fetal tissues. Offspring hypothyroid utero poorly adapted to regulate body temperature at risk becoming obese insulin resistant childhood. The mechanisms by which thyroid development fetus, however, unclear. Methods: This study examined structure, transcriptome, protein...