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Publications (48)
Pancreatic Ductal Adenocarcinoma (PDAC) is highly resistant to chemotherapy. Effective alternative therapies have yet to emerge, as chemotherapy remains the best available systemic treatment. However, the discovery of safe and available adjuncts to enhance chemotherapeutic efficacy can still improve survival outcomes. We show that a hyperglycemic s...
Background
Crohn’s disease (CD) patients demonstrate distinct intestinal microbial compositions and metabolic characteristics compared to unaffected controls. However, the impact of inflammation and underlying genetic risk on these microbial profiles and their relationship to disease phenotype are unclear. We used lavage sampling to characterize th...
Pancreatic cancer (Pancreatic Ductal Adenocarcinoma; PDAC) is highly resistant to
chemotherapy. Effective alternative therapies have yet to emerge, leaving chemotherapy as the best available systematic treatment. The discovery of safe and available adjuncts that improve chemotherapeutic efficacy would potentially improve survival outcomes. We show...
Obesity has repeatedly been linked to reorganization of the gut microbiome, yet to this point obesity therapeutics have been targeted exclusively toward the human host. Here we show that gut microbe-targeted inhibition of the trimethylamine N-oxide (TMAO) pathway protects mice against the metabolic disturbances associated with diet-induced obesity...
Metabolites from the microbiome influence human, animal, and environmental health, but the diversity and functional roles of these compounds have only begun to be elucidated. Comprehensively characterizing these molecules are significant challenges, as it requires expertise in analytical methods, such as mass spectrometry and nuclear magnetic reson...
Introduction
Ex vivo normothermic limb perfusion (EVNLP) provides several advantages for the preservation of limbs following amputation: the ability to maintain oxygenation and temperature of the limb close to physiological values, a perfusion solution providing all necessary nutrients at optimal concentrations, and the ability to maintain physiolo...
Our laboratory and others have use radiation metabolomics to assess responses in order to develop biomarkers reflecting exposure and level of injury. To expand the types of exposure and compare to previously published results, metabolomic analysis has been carried out using serum samples from mice exposed to 137Cs internal emitters. Animals were in...
Lack of standardized applications of bioinformatics and statistical approaches for pre- and postprocessing of global metabolomic profiling data sets collected using high-resolution mass spectrometry platforms remains an inadequately addressed issue in the field. Several publications now recognize that data analysis outcome variability is caused by...
In the past decade, the field of LC-MS based metabolomics has transformed from an obscure specialty into a major “-omics” platform for studying metabolic processes and biomolecular characterization. However, as a whole the field is still very fractured, as the nature of the instrumentation and of the information produced by the platform essentially...
The modern application of mass spectrometry-based metabolomics to the field of radiation-assessment and biodosimetry has allowed for efforts to develop prompt screenings to identify biomarkers related to radiation exposure. Our previous work on radiation assessment in easily accessible biofluids (such as urine, blood, saliva) has revealed unique me...
Background:
The diagnosis of Behçet's disease (BD) remains challenging due to the lack of diagnostic biomarkers. This study aims to identify potential serum metabolites associated with BD and its disease activity.
Methods:
Medical records and serum samples of 24 pretreated BD patients, 12 post-treated BD patients, and age-matched healthy control...
Intestinal dysbiosis is thought to confer susceptibility to inflammatory bowel disease (IBD), but it is unknown whether dynamic changes in the microbiome contribute to fluctuations in disease activity. We explored this question using mice with intestine-specific deletion of C1galt1 (also known as T-synthase) (Tsyn mice). These mice develop spontane...
Alcoholic liver disease is a pathological condition caused by over-consumption of alcohol. Due to the high morbidity and mortality associated with this disease, there remains a need to elucidate the molecular mechanisms underlying its etiology and to develop new treatments. Since peroxisome proliferator-activated receptor-β/δ (PPARβ/δ) modulates et...
Medical responders to radiological and nuclear disasters currently lack sufficient high-throughput and minimally invasive biodosimetry tools to assess exposure and injury in the affected populations. For this reason, we have focused on developing robust radiation exposure biomarkers in easily accessible biofluids such as urine, serum and feces. Whi...
Background & Aims
Microbes may increase susceptibility to inflammatory bowel disease (IBD) by producing bioactive metabolites that affect immune activity and epithelial function. We undertook a family based study to identify microbial and metabolic features of IBD that may represent a predisease risk state when found in healthy first-degree relativ...
Table of contents
O1 Regulation of genes by telomere length over long distances
Jerry W. Shay
O2 The microtubule destabilizer KIF2A regulates the postnatal establishment of neuronal circuits in addition to prenatal cell survival, cell migration, and axon elongation, and its loss leading to malformation of cortical development and severe epilepsy
No...
With the safety of existing nuclear power plants being brought into question after the Fukushima disaster and the increased level of concern over terrorism-sponsored use of improvised nuclear devices, it is more crucial to develop well-defined radiation injury markers in easily accessible biofluids to help emergency-responders with injury assessmen...
Despite considerable research into the environmental risks and biological effects of exposure to external beam gamma rays, incorporation of radionuclides has largely been understudied. This dosimetry and exposure risk assessment is challenging for first responders in the field during a nuclear or radiological event. Therefore, we have developed a w...
Internal emitters such as Strontium-90 ((90)Sr) pose a substantial health risk during and immediately after a nuclear disaster or detonation of an improvised device. The environmental persistency and potency of (90)Sr calls for urgent development of high-throughput tests to establish levels of exposure and to help triage potentially exposed individ...
One of the consequences in analyzing biological data from noisy sources, such as human subjects, is the sheer variability of experimentally irrelevant factors that cannot be controlled for. This holds true especially in metabolomics, the global study of small molecules in a particular system. While metabolomics can offer deep quantitative insight i...
In this study ultra-performance liquid chromatography (UPLC) coupled with time of flight mass spectrometry in the MSE mode was used for rapid and comprehensive analysis of metabolites in the serum of mice exposed to internal exposure by Cesium-137 (137Cs). The effects of exposure to 137Cs were studied at several time-points after injection of 137Cs...
Metabolomics has been shown to have utility in assessing responses to exposure by ionizing radiation (IR) in easily accessible biofluids such as urine. Most studies to date from our laboratory and others have employed γ-irradiation at relatively high dose rates (HDR), but many environmental exposure scenarios will probably be at relatively low dose...
Fucosyltransferase 2 (FUT2) is an enzyme that is responsible for the synthesis of the H antigen in body fluids and on the intestinal mucosa. The H antigen is an oligosaccharide moiety that acts as both an attachment site and carbon source for intestinal bacteria. Non-secretors, who are homozygous for the loss-of-function alleles of FUT2 gene (sese)...
Cesium-137 is a fission product of uranium and plutonium in nuclear reactors and is released in large quantities during nuclear explosions or detonation of an improvised device containing this isotope. This environmentally persistent radionuclide undergoes radioactive decay with the emission of beta particles as well as gamma radiation. Exposure to...
Metabolomics, the global study of small molecules in a particular system, has in the past few years risen to become a primary -omics platform for the study of metabolic processes. With the ever-increasing pool of quantitative data yielded from metabolomic research, specialized methods and tools with which to analyze and extract meaningful conclusio...
Because of the significant morbidity and lethality caused by alcoholic liver disease (ALD), there remains a need to elucidate the regulatory mechanisms that can be targeted to prevent and treat ALD. Towards this goal, minimally invasive biomarker discovery represents an outstanding approach for these purposes. The mechanisms underlying ALD include...
Background
Consistent compositional shifts in the gut microbiota are observed in IBD and other chronic intestinal disorders and may contribute to pathogenesis. The identities of microbial biomolecular mechanisms and metabolic products responsible for disease phenotypes remain to be determined, as do the means by which such microbial functions may b...