Stewart Graham

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Verified

Stewart verified their affiliation via an institutional email.

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• PhD, MSc, BSc (Hons)
• Chair at Beaumont Health System

Azaspiracid (AZA) poisoning was unknown until 1995 when shellfish harvested in Ireland caused illness manifesting by vomiting and diarrhoea. Further in vivo/vitro studies showed neurotoxicity linked with AZA exposure. However, the biological target of the toxin which will help explain such potent neurological activity is still unknown. A region of...

This study combined high resolution mass spectrometry (HRMS), advanced chemometrics and pathway enrichment analysis to analyse the blood metabolome of patients attending the memory clinic: cases of mild cognitive impairment (MCI; n = 16), cases of MCI who upon subsequent follow-up developed Alzheimer’s disease (MCI_AD; n = 19), and healthy age-matc...

Disease-, age-, and gender-associated changes in brain copper, iron, and zinc were assessed in postmortem neocortical tissue (Brodmann area 7) from patients with moderate Alzheimer's disease (AD) (n = 14), severe AD (n = 28), dementia with Lewy bodies (n = 15), and normal age-matched control subjects (n = 26). Copper was lower (20%; p < 0.001) and...

Brain tissue from so-called Alzheimer’s disease (AD) mouse models has previously been examined using 1H NMR-metabolomics, but comparable information concerning human AD is negligible. Since no animal model recapitulates all the features of human AD we undertook the first 1H NMR-metabolomics investigation of human AD brain tissue. Human post-mortem...

A study combining high resolution mass spectrometry (LC-QTof-MS) and chemometrics for the analysis of post-mortem brain tissue from subjects with Alzheimer’s disease (AD) (n=15) and healthy age-matched controls (n=15) was undertaken. The huge potential of this metabolomics approach for distinguishing AD cases is underlined by the correct prediction...

Prenatal sonographic diagnosis of congenital heart disease (CHD) can lead to improved morbidity and mortality. However, the diagnostic accuracy of ultrasound, the sole prenatal screening tool, remains limited. Failed prenatal or early newborn detection of cyanotic CHD (CCHD) can have disastrous consequences. We therefore sought to use a Precision F...

Background: Huntington’s disease (HD) is a multifaceted neurological disorder characterized by the progressive deterioration of motor, cognitive, and psychiatric functions. Despite a limited understanding of its pathogenesis, research has implicated abnormal trinucleotide cytosine-adenine-guanine CAG repeat expansion in the huntingtin gene (HTT) as...

Background Lewy body diseases, including dementia with Lewy bodies (DLB), are characterized by α‐synuclein accumulation, leading to dementia. Previous studies suggest distinct epigenetic and metabolomic profiles in DLB. Objective This study aims to identify diagnostic biomarkers by analyzing the methylome and metabolome in the Brodmann area 7 of p...

Background/Objectives: Thus far, no studies have examined the relationship between fruit and vegetable (F and V) intake, urinary metabolite quantities, and weight change. Therefore, the aim of the current study was to explore changes in urinary metabolomic profiles during and after a 10-week weight loss intervention where participants were prescrib...

Background The unprecedented increase in the older population and ever-increasing incidence of dementia are leading to a “silver tsunami” in upcoming decades. To combat multimorbidity and maintain daily activities, elderly people face a high prevalence of polypharmacy. However, how these medications affect dementia-related pathology, such as Alzhei...

Metabolomics and lipidomics are pivotal in understanding phenotypic variations beyond genomics. However, quantification and comparability of mass spectrometry (MS)-derived data are challenging. Standardised assays can enhance data comparability, enabling applications in multi-center epidemiological and clinical studies. Here we evaluated the perfor...

Epidemiological evidence suggests an association between dioxin and dioxin-like compound (DLC) exposure and human liver disease. The prototypical DLC, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), has been shown to induce the progression of reversible hepatic steatosis to steatohepatitis with periportal fibrosis and biliary hyperplasia in mice. Altho...

Ectopic pregnancy (EP) is the leading cause of maternal morbidity and mortality in the first trimester. Using an untargeted metabolomic approach, we sought to identify putative plasma biomarkers using tandem liquid chromatography–mass spectrometry for the detection of tubal EP. This case-control study included the prospective recruitment of 50 tuba...

This study evaluated the effects of maternal supplementation during pre- and postpartum of a Bacillus-based direct-fed microbial (DFM) on plasma metabolome of Bos indicus-influenced cow-calf pairs. On d 0, 72 pregnant Brangus crossbred beef heifers (20 to 22 mo of age) were stratified by their initial body weight (BW; 431 ± 31 kg) and body conditio...

Background Metabolic dysfunction–associated steatotic liver disease (MASLD) is strongly associated with obesity. Sex and age affect MASLD prevalence and pathophysiology. The use of animal models fed Western-style diets is vital for investigating the molecular mechanisms contributing to metabolic dysregulation and for facilitating novel drug target...

Introduction Preeclampsia (PreE) remains a major source of maternal and newborn complications. Prenatal prediction of these complications could significantly improve pregnancy management. Objectives Using metabolomic analysis we investigated the prenatal prediction of maternal and newborn complications in early and late PreE and investigated the p...

Bile acids (BAs) are steroid detergents in bile that contribute to the absorption of fats and fat-soluble vitamins while shaping the gut microbiome because of their antimicrobial properties1–4. Here we identify the enzyme responsible for a mechanism of BA metabolism by the gut microbiota involving amino acid conjugation to the acyl-site of BAs, thu...

Background The ever‐increasing incidence of Alzheimer’s disease (AD) and the lack of effective therapeutics to treat the disease are leading to a “silver tsunami”. Current FDA‐approved drugs to treat the disease are limited as their benefit is simply momentary relief of the symptoms. Due to the chronic and progressive nature of AD, patients are rou...

Huntington’s disease (HD) is a progressive, fatal neurodegenerative disease characterized by motor, cognitive, and psychiatric symptoms. The precise mechanisms of HD progression are poorly understood; however, it is known that there is an expansion of the trinucleotide cytosine-adenine-guanine (CAG) repeat in the Huntingtin gene. Important new stra...

Traumatic brain injury (TBI) is a major cause of mortality and disability worldwide, particularly among individuals under the age of 45. It is a complex, and heterogeneous disease with a multifaceted pathophysiology that remains to be elucidated. Metabolomics has the potential to identify metabolic pathways and unique biochemical profiles associate...

Introduction Consumption of a Mediterranean diet (MD) has established health benefits, and the identification of novel biomarkers could enable objective monitoring of dietary pattern adherence. Objectives The present investigation performed untargeted metabolomics on blood plasma from a controlled study of MD adherence, to identify novel blood-bas...

The impact of environmental factors on epigenetic changes is well established, and cellular function is determined not only by the genome but also by interacting partners such as metabolites. Given the significant impact of metabolism on disease progression, exploring the interaction between the metabolome and epigenome may offer new insights into...

Endometrial inflammation is associated with reduced pregnancy per artificial insemination (AI) and increased pregnancy loss in cows. It was hypothesized that induced endometritis alters histotroph composition and induces inflammatory signatures on conceptus that compromise development. In experiment 1, lactating cows were assigned to control (CON;...

Background Alzheimer’s disease (AD) is the most common form of dementia, accounting for 80% of all cases. Mild cognitive impairment (MCI) is a transitional state between normal aging and AD. Early detection is crucial, as irreversible brain damage occurs before symptoms manifest. Objective This study aimed to identify potential biomarkers for earl...

• Introduction: Consumption of a Mediterranean diet (MD) has established health benefits, and the identification of novel biomarkers could enable objective monitoring of dietary pattern adherence. • Objectives: The present investigation performed untargeted metabolomics on blood plasma from a controlled study of MD adherence, to identify novel bloo...

In brief The concentration of progesterone through the estrous cycle modulates uterine function to affect the luminal metabolome. This paper reports that the dynamic changes in the bovine uterine luminal metabolome during diestrus are independent of the concentration of progesterone in the previous cycle. Abstract In cattle, the concentration of s...

Introduction The impact of maternal coronavirus disease 2019 (COVID-19) infection on fetal health remains to be precisely characterized. Objectives Using metabolomic profiling of newborn umbilical cord blood, we aimed to investigate the potential fetal biological consequences of maternal COVID-19 infection. Methods Cord blood plasma samples from...

This prospective observational study aimed to evaluate the association of metabolomic alterations with weight loss outcomes following sleeve gastrectomy (SG). We evaluated the metabolomic profile of serum and feces prior to SG and three months post-SG, along with weight loss outcomes in 45 adults with obesity. The percent total weight loss for the...

Precision neurology combines high-throughput technologies and statistical modeling to identify novel disease pathways and predictive biomarkers in Alzheimer’s disease (AD). Brain cytochrome P450 (CYP) genes are major regulators of cholesterol, sex hormone, and xenobiotic metabolism, and they could play important roles in neurodegenerative disorders...

Dementia with Lewy bodies (DLB) is a common form of dementia with known genetic and environmental interactions. However, the underlying epigenetic mechanisms which reflect these gene-environment interactions are poorly studied. Herein, we measure genome-wide DNA methylation profiles of post-mortem brain tissue (Broadmann area 7) from 15 pathologica...

Introduction: The impact of maternal coronavirus disease 2019 (COVID-19) infection on fetal health remains to be precisely characterized. Objectives: Using metabolomic profiling of newborn umbilical cord blood, we aimed to investigate the potential fetal biological consequences of maternal COVID-19 infection. Methods: Cord blood serum samples from...

SARS-CoV-2 corona virus causes a multi-faceted and poorly defined clinical and pathological phenotype involving hyperinflammation, cytokine release, and long-term cognitive deficits, with an undefined neuropathological mechanism. Inflammation increases the activity of the kynurenine pathway, which is linked to neurodegenerative and psychiatric diso...

Background: Despite extensive efforts, significant gaps remain in our understanding of Alzheimer's disease (AD) pathophysiology. Novel approaches using circulating cell-free DNA (cfDNA) have the potential to revolutionize our understanding of neurodegenerative disorders. Methods: We performed DNA methylation profiling of cfDNA from AD patients a...

Parkinson’s disease (PD) is second most prevalent neurodegenerative disorder following Alzheimer’s disease. Parkinson’s disease is hypothesized to be caused by a multifaceted interplay between genetic and environmental factors. Herein, and for the first time, we describe the integration of metabolomics and epigenetics (genome-wide DNA methylation;...

INTRODUCTION Determining significant metabolic changes in Dementia with Lewy Bodies (DLB), a complex and multifactorial neurodegenerative disease, requires, in addition to the analysis of concentration changes, a deep understanding of functional modifications in the context of metabolic networks. METHODS Brain metabolomics data from DLB patients an...

Alzheimer’s disease (AD) is reported to be closely linked with abnormal lipid metabolism. To gain a more comprehensive understanding of what causes AD and its subsequent development, we profiled the lipidome of postmortem (PM) human brains (neocortex) of people with a range of AD pathology (Braak 0–6). Using high-resolution mass spectrometry, we em...

Introduction Itch is an unpleasant sensation that elicits the desire to scratch and can cause great distress, particularly in persons with venous ulcers. This pilot study explored the difference in metabolic profiles for wound exudate and serum in patients with or without venous ulcer wound itch. Methods Patient information, wound assessment, and...

Objective To identify maternal second and third trimester urine metabolomic biomarkers for the detection of fetal congenital heart defects (CHDs). Study design This was a prospective study. Metabolomic analysis of randomly collected maternal urine was performed, comparing pregnancies with isolated, non-syndromic CHDs versus unaffected controls. Ma...

We evaluated the utility of leucocyte epigenomic-biomarkers for Alzheimer’s Disease (AD) detection and elucidates its molecular pathogeneses. Genome-wide DNA methylation analysis was performed using the Infinium MethylationEPIC BeadChip array in 24 late-onset AD (LOAD) and 24 cognitively healthy subjects. Data were analyzed using six Artificial Int...

The gut microbiome can impact brain health and is altered in Parkinson’s disease (PD). The vermiform appendix is a lymphoid tissue in the cecum implicated in the storage and regulation of the gut microbiota. We sought to determine whether the appendix microbiome is altered in PD and to analyze the biological consequences of the microbial alteration...

Branch Chain Amino Acids (BCAA) have recently been implicated in Alzheimer’s Disease (AD). We previously showed that low dose brain radiation (RT) [5 fractions of 2 Gy] reduces amyloid-beta plaque burden and results in improved cognition in the APP/PS1 model of AD. In this study we investigated whether this schedule of radiation altered the metabol...

CSF from unique groups of Parkinson's disease (PD) patients was biochemically profiled to identify previously unreported metabolic pathways linked to PD pathogenesis, and novel biochemical biomarkers of the disease were characterized. Utilizing both 1 H NMR and DI-LC-MS/MS we quantitatively profiled CSF from patients with sporadic PD (n = 20) and t...

Background Currently, there is no objective, clinically available tool for the accurate diagnosis of Alzheimer’s disease (AD). There is a pressing need for a novel, minimally invasive, cost friendly, and easily accessible tool to diagnose AD, assess disease severity, and prognosticate course. Metabolomics is a promising tool for discovery of new, b...

The gut microbiome can impact brain health and is altered in Parkinson’s disease (PD) patients. Here, we investigate changes in the functional microbiome in the appendix of PD patients relative to controls by metatranscriptomic analysis. We find microbial dysbiosis affecting lipid metabolism, particularly an upregulation of bacteria responsible for...

The lack of sensitive and specific biomarkers for the early detection of mild cognitive impairment (MCI) and Alzheimer’s disease (AD) is a major hurdle to improving patient management. A targeted, quantitative metabolomics approach using both 1H NMR and mass spectrometry was employed to investigate the performance of urine metabolites as potential...

Epilepsy not-otherwise-specified (ENOS) is one of the most common causes of chronic disorders impacting human health, with complex multifactorial etiology and clinical presentation. Understanding the metabolic processes associated with the disorder may aid in the discovery of preventive and therapeutic measures. Post-mortem brain samples were harve...

A longstanding issue in the field of nutrition is the potential inaccuracy of methods traditionally used for dietary assessment (i.e. food diaries and food frequency questionnaires). It is possible to overcome the limitations and biases of these techniques by combining them with analytical measurements in human biofluids. Metabolomic technologies a...

Cerebral palsy (CP), defined as a group of nonprogressive disorders of movement and posture, is the most common cause of severe neurodisability in children. The prevalence of CP is the same across the globe, affecting approximately 17 million people worldwide. Cerebral Palsy is an umbrella term used to describe the disease due to its inherent heter...

Glioblastoma is the most common primary malignant brain tumor in adults. Despite aggressive treatment, outcomes remain poor with few long-term survivors. Therefore, considerable effort is being made to identify novel therapies for this malignancy. Targeting tumor metabolism represents a promising therapeutic strategy and activation of fatty acid ox...

Disruptions of brain metabolism are considered integral to the pathogenesis of dementia, but thus far little is known of how dementia with Lewy bodies (DLB) impacts the brain metabolome. DLB is less well known than other neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease which is perhaps why it is under-investigated. This explor...

IntroductionAutism spectrum disorder (ASD) is a group of neurodevelopmental disorders characterized by deficiencies in social interactions and communication, combined with restricted and repetitive behavioral issues.Objectives As little is known about the etiopathophysiology of ASD and early diagnosis is relatively subjective, we aim to employ a ta...

Despite advances in molecularly characterizing glioblastoma (GBM), metabolic alterations driving its aggressive phenotype are only beginning to be recognized. Integrative cross-platform analysis coupling global metabolomic and gene expression profiling on patient-derived glioma identified fatty acid β-oxidation (FAO) as a metabolic node in GBM. We...

Background: CSF from unique groups of Parkinson’s disease (PD) patients were biochemically profiled to identify previously unreported metabolic pathways linked to PD pathogenesis and novel biochemical biomarkers of the disease were characterized. Methods: Utilizing both ¹H NMR and DI-LC-MS/MS we quantitatively profiled CSF from patients with sporad...

Introduction: Fetal growth restriction (FGR), viz., birth weight <10th percentile is a common pregnancy complication which increases the risk of adverse fetal and newborn outcomes. The placenta is the key organ for fetal growth as it controls oxygen and nutrient availability. This study aims to elucidate the mechanisms of and identify putative plac...

Glioblastoma represents an aggressive, primary brain tumor with limited treatment options. Despite advances in molecularly characterizing glioblastoma, metabolic alterations driving its aggressive phenotype are only beginning to be recognized. Integrative cross-platform analyses coupling global metabolomic and gene expression profiling identified a...

Introduction Ectopic pregnancy (EP) is a potentially life-threatening condition and early diagnosis still remains a challenge, causing a delay in management leading to tubal rupture. Objectives To identify putative plasma biomarkers for the detection of tubal EP and elucidate altered biochemical pathways in EP compared to intrauterine pregnancies....

The Mediterranean diet (MD) is a dietary pattern well-known for its benefits in disease prevention. Monitoring adherence to the MD could be improved by discovery of novel dietary biomarkers. The MEDiterranean Diet in Northern Ireland (MEDDINI) intervention study monitored the adherence of participants to the MD for up to 12 months. This investigati...

Objective To interrogate the pathogenesis of intrauterine growth restriction (IUGR) and apply Artificial Intelligence (AI) techniques to multi-platform i.e. nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (MS) based metabolomic analysis for the prediction of IUGR. Materials and methods MS and NMR based metabolomic analysis were...

Model performances in terms of accuracies, sensitivities and specificities (average and standard deviations) and significance score when samples grouping was taken place according to 5th %le criteria for each model that provided various panel of metabolites for 5th percentile. (DOCX)

Results of univariate analysis comparing concentration of metabolites in serum obtained cord blood of IUGR sufferers and corresponding healthy controls. (DOCX)

Comparison of demographics and clinical assessments. (DOCX)

Optimum C-γ pairs for each metabolite set and corresponding model performances in terms of accuracies (average and standard deviations) and significance score for 10th percentile. (DOCX)

Cerebral palsy (CP) is one of the most common causes of motor disability in childhood, with complex and heterogeneous etiopathophysiology and clinical presentation. Understanding the metabolic processes associated with the disease may aid in the discovery of preventive measures and therapy. Tissue samples (caudate nucleus) were obtained from post-m...

Introduction Epithelial ovarian cancer (EOC) remains the leading cause of death from gynecologic malignancies and has an alarming global fatality rate. Besides the differences in underlying pathogenesis, distinguishing between high grade (HG) and low grade (LG) EOC is imperative for the prediction of disease progression and responsiveness to chemot...

Objective: To evaluate the utility of Artificial Intelligence i.e. Deep Learning (DL) and other machine learning techniques for the prediction of important pregnancy outcomes in asymptomatic short cervical length (CL). Method: The amniotic fluid (AF) had been obtained from second trimester patients with asymptomatic women with short cervical len...

For people with Parkinson's disease (PD), considered the most common neurodegenerative disease behind Alzheimer's disease, accurate diagnosis is dependent on many factors; however, misdiagnosis is extremely common in the prodromal phases of the disease, when treatment is thought to be most effective. Currently, there are no robust biomarkers that a...

Brain is a lipid-rich tissue, and fatty acids (FAs) play a crucial role in brain function, including neuronal cell growth and development. This study used GC-MS to survey all detectable FAs in the human parietal cortex (Brodmann area 7). These FAs were accurately quantified in 27 cognitively normal age-matched controls, 16 cases of moderate Alzheim...

Introduction Melanoma is a highly aggressive malignancy and is currently one of the fastest growing cancers worldwide. While early stage (I and II) disease is highly curable with excellent prognosis, mortality rates rise dramatically after distant spread. We sought to identify differences in the metabolome of melanoma patients to further elucidate...

Glioblastoma (GBM) represents an aggressive brain tumor with limited treatment options. Although considerable progress has been made in understanding molecular alterations unique to these tumors, the diverse metabolic programs driving their aggressive phenotype are only beginning to be recognized. As an initial investigation, using a library consis...

Glioblastoma (GBM) is an aggressive brain tumor with limited treatment options. Immune checkpoint inhibitors designed to revert tumor-induced immune suppression have emerged as potent anti-cancer therapies. We performed cross-platform analyses coupling global metabolomic and gene-expression profiling in patient-derived gliomas. We identified aberra...

Parkinson’s disease is the second most common neurodegenerative disease. In the vast majority of cases the origin is not genetic and the cause is not well understood, although progressive accumulation of α-synuclein aggregates appears central to the pathogenesis. Currently, treatments that slow disease progression are lacking and there are no robus...

Purpose: Immune checkpoint inhibitors designed to revert tumor-induced immune suppression have emerged as potent anti-cancer therapies. Tryptophan metabolism represents an immune checkpoint and targeting this pathway's rate limiting enzyme IDO1 is actively being investigated clinically. Here, we studied the intermediary metabolism of tryptophan me...

Huntington's disease (HD) is a devastating, progressive neurodegenerative disease with a distinct phenotype characterized by chorea and dystonia, incoordination, cognitive decline and behavioral difficulties. The precise mechanisms of HD progression are poorly understood; however, it is known that there is an expansion of the trinucleotide cytosine...

Tumour angiogenesis is an important hallmark of cancer and the study of its metabolic adaptations, downstream to any cellular change, can reveal attractive targets for inhibiting cancer growth. In the tumour microenvironment, endothelial cells (ECs) interact with heterogeneous tumour cell types that drive angiogenesis and metastasis. In this study...

Fragmentation spectra and the matching spectral profile from the mass spectral library for the identified metabolites. (PDF)