Gary Siuzdak - Profile on Academia.edu (original) (raw)

Papers by Gary Siuzdak

Metabolomics : Official journal of the Metabolomic Society, 2015

Heat maps are a commonly used visualization tool for metabolomic data where the relative abundanc... more Heat maps are a commonly used visualization tool for metabolomic data where the relative abundance of ions detected in each sample is represented with color intensity. A limitation of applying heat maps to global metabolomic data, however, is the large number of ions that have to be displayed and the lack of information provided about important metabolomic parameters such as m/z and retention time. Here we address these challenges by introducing the interactive cluster heat map in the data-processing software XCMS Online. XCMS Online (xcmsonline.scripps.edu) is a cloud-based informatic platform designed to process, statistically evaluate, and visualize mass-spectrometry based metabolomic data. An interactive heat map is provided for all data processed by XCMS Online. The heat map is clickable, allowing users to zoom and explore specific metabolite metadata (EICs, Box-and-whisker plots, mass spectra) that are linked to the METLIN metabolite database. The utility of the XCMS interacti...

Scientific Reports, 2015

The human circulatory system consists of arterial blood that delivers nutrients to tissues, and v... more The human circulatory system consists of arterial blood that delivers nutrients to tissues, and venous blood that removes the metabolic by-products. Although it is well established that arterial blood generally has higher concentrations of glucose and oxygen relative to venous blood, a comprehensive biochemical characterization of arteriovenous differences has not yet been reported.

Blood, Jan 14, 2015

In many deep vein thrombosis and pulmonary embolism (VTE) patients, biomarkers or genetic risk fa... more In many deep vein thrombosis and pulmonary embolism (VTE) patients, biomarkers or genetic risk factors have not been identified. To discover novel plasma metabolites associated with VTE risk, we employed liquid chromatography-mass spectrometry-based untargeted metabolomics which does not target any specific metabolites. Using the Scripps Venous Thrombosis Registry population for a case-control study, we discovered that 10:1 and 16:1 acylcarnitines were low in plasmas of the VTE patient group compared to matched controls. Data from targeted metabolomics studies showed that several long-chain acylcarnitines (10:1, 12:0, 12:2, 18:1 and 18:2) were lower in the VTE group. Clotting assays were used to evaluate a causal relationship for low acylcarnitines in VTE patients. Various acylcarnitines inhibited factor Xa-initiated clotting. Inhibition of factor Xa by acylcarnitines was greater for longer acyl chain. Mechanistic studies showed that 16:0 acylcarnitine had anticoagulant activity in ...

Journal of Trauma-injury Infection and Critical Care, 2007

Background: Systemic inflammatory response syndrome (SIRS) represents a host response to various ... more Background: Systemic inflammatory response syndrome (SIRS) represents a host response to various insults. Recent advances have demonstrated an interconnection be- tween inflammation, complement, and co- agulation. This experiment was designed to evaluate differences in plasma protein pro- files between clinically identical patients: septic versus uninfected SIRS patients, prior to clinical diagnosis of infection. Methods: Patients admitted to an in- tensive

Electrospray ion mobility spectrometry of intact viruses

Spectroscopy, 2004

ABSTRACT

Cell Metabolism, 2015

Highlights d Colonic mucosal biofilms alter the cancer metabolome d N 1 , N 12 -diacetylspermine ... more Highlights d Colonic mucosal biofilms alter the cancer metabolome d N 1 , N 12 -diacetylspermine was significantly upregulated in tissues with biofilms d Biofilms create conditions conducive to oncogenic transformation in colon cells d Global isotope metabolomics reveals the metabolite fate of N 1 , N 12 -diacetylspermine

specificity similarity to both mammalian Oat1 and Oat3 The flounder organic anion transporter fOa... more specificity similarity to both mammalian Oat1 and Oat3 The flounder organic anion transporter fOat has sequence, function, and substrate (PDF) (Full Text) (Abstract)

Discriminating precursors of common fragments for large-scale metabolite profiling by triple quadrupole mass spectrometry

Bioinformatics (Oxford, England), Jan 16, 2015

The goal of large-scale metabolite profiling is to compare the relative concentrations of as many... more The goal of large-scale metabolite profiling is to compare the relative concentrations of as many metabolites extracted from biological samples as possible. This is typically accomplished by measuring the abundances of thousands of ions with high-resolution and high mass accuracy mass spectrometers. Although the data from these instruments provide a comprehensive fingerprint of each sample, identifying the structures of the thousands of detected ions is still challenging and time intensive. An alternative, less-comprehensive approach is to use triple quadrupole (QqQ) mass spectrometry to analyze predetermined sets of metabolites (typically fewer than several hundred). This is done using authentic standards to develop QqQ experiments that specifically detect only the targeted metabolites, with the advantage that the need for ion identification after profiling is eliminated. Here, we propose a framework to extend the application of QqQ mass spectrometers to large-scale metabolite prof...

Nature, Jan 20, 1999

Desorption mass spectrometry has undergone significant improvements since the original experiment... more Desorption mass spectrometry has undergone significant improvements since the original experiments were performed more than 90 years ago. The most dramatic change occurred in the early 1980s with the introduction of an organic matrix to transfer energy to the analyte. This reduces ion fragmentation but also introduces background ions from the matrix. Here we describe a matrix-free strategy for biomolecular mass spectrometry based on pulsed-laser desorption-ionization from a porous silicon surface. Our method uses porous silicon to trap analytes deposited on the surface, and laser irradiation to vaporize and ionize them. We show that the method works at femtomole and attomole levels of analyte, and induces little or no fragmentation, in contrast to what is typically observed with other such approaches. The ability to perform these measurements without a matrix also makes it more amenable to small-molecule analysis. Chemical and structural modification of the porous silicon has enable...

Crystallographically identical virus capsids display different properties in solution

Nature structural biology, 1999

Either your web browser doesn&amp;amp;#x27;t support Javascript or it is currently turned... more Either your web browser doesn&amp;amp;#x27;t support Javascript or it is currently turned off. In the latter case, please turn on Javascript support in your web browser and reload this page. ... Crystallographically identical virus capsids display different properties in solution. ... Find all citations by this ...

Desorption/ionization on silicon (DIOS): A diverse mass spectrometry platform for protein characterization

Proceedings of The National Academy of Sciences, 2001

Since the advent of matrix-assisted laser desorption/ionization and electrospray ionization, mass... more Since the advent of matrix-assisted laser desorption/ionization and electrospray ionization, mass spectrometry has played an increasingly important role in protein functional characterization, identification, and structural analysis. Expanding this role, desorption/ionization on silicon (DIOS) is a new approach that allows for the analysis of proteins and related small molecules. Despite the absence of matrix, DIOS-MS yields little or no fragmentation and

Genome Biology, 2007

The obesity epidemic has prompted the search for candidate genes capable of influencing adipose f... more The obesity epidemic has prompted the search for candidate genes capable of influencing adipose function. One such candidate, that encoding phospholipid scramblase 3 (PLSCR3), was recently identified, as genetic deletion of it led to lipid accumulation in abdominal fat pads and changes characteristic of metabolic syndrome. Because adipose tissue is increasingly recognized as an endocrine organ, capable of releasing small molecules that modulate disparate physiological processes, we examined the plasma from wild-type, Plscr1-/-, Plscr3-/-and Plscr1&3-/mice. Using an untargeted comprehensive metabolite profiling approach coupled with targeted gene expression analyses, the perturbed biochemistry and functional redundancy of PLSCR proteins was assessed.

Journal of Proteome Research, 2007

Mass spectrometry (MS) is an established technology in drug metabolite analysis and is now expand... more Mass spectrometry (MS) is an established technology in drug metabolite analysis and is now expanding into endogenous metabolite research. Its utility derives from its wide dynamic range, reproducible quantitative analysis, and the ability to analyze biofluids with extreme molecular complexity. The aims of developing mass spectrometry for metabolomics range from understanding basic biochemistry to biomarker discovery and the structural characterization

Aspects of oligonucleotide and peptide sequencing with MALDI and electrospray mass spectrometry

Bioorganic & Medicinal Chemistry, 1998

Biopolymer sequencing with mass spectrometry has become increasingly important and accessible wit... more Biopolymer sequencing with mass spectrometry has become increasingly important and accessible with the development of matrix-assisted laser desorption/ionization (MALDI) and electrospray ionization (ESI). Here we examine the use of sequential digestion for the rapid identification of proteolytic fragments, in turn highlighting the general utility of enzymatic MALDI ladder sequencing and ESI tandem mass spectrometry. Analyses were performed on oligonucleotides ranging

Quantitative Analysis with Desorption/Ionization on Silicon Mass Spectrometry Using Electrospray Deposition

Analytical Chemistry, 2003

Desorption/ionization on silicon mass spectrometry (DIOS-MS) is demonstrated as a quantitative an... more Desorption/ionization on silicon mass spectrometry (DIOS-MS) is demonstrated as a quantitative analytical tool when coupled to electrospray deposition (ESD). In this study, we illustrate the utility of DIOS-MS in the quantitative analysis of a peptide and two amino acids with deuterated and structural analogues used as internal standards. An important feature of this approach is the incorporation of ESD to improve sample homogeneity across the porous silicon surface. ESD allowed for a marked improvement in quantitative analysis due to its applicability to LC-DIOS, and because of the absence of matrix, sample can be deposited at very low flow rates (150 nL/min). Experiments comparing the traditional dried droplet and ESD methods show that ESD samples exhibit significantly improved quantitation and much higher sample-to-sample reproducibility.

Innovation: Metabolomics: the apogee of the omics trilogy

Metabolites, the chemical entities that are transformed during metabolism, provide a functional r... more Metabolites, the chemical entities that are transformed during metabolism, provide a functional readout of cellular biochemistry. With emerging technologies in mass spectrometry, thousands of metabolites can now be quantitatively measured from minimal amounts of biological material, which has thereby enabled systems-level analyses. By performing global metabolite profiling, also known as untargeted metabolomics, new discoveries linking cellular pathways to biological mechanism are being revealed and are shaping our understanding of cell biology, physiology and medicine.

Folding of apomyoglobin is characterized by formation of a compact intermediate that contains sub... more Folding of apomyoglobin is characterized by formation of a compact intermediate that contains substantial helicity. To determine whether this intermediate is obligatory or whether the protein can fold directly into the native state via an alternate parallel pathway, we have combined quench-flow hydrogen-exchange pulse labeling techniques with electrospray ionization mass spectrometry. The mass spectra of apomyoglobin obtained at various refolding times suggest that apomyoglobin indeed folds through a single pathway containing an obligatory intermediate with a significant hydrogenbonded secondary structure content.

Analytical Chemistry, 1999

Nanoelectrospray ionization (nanoESI) mass spectrometry was performed on naturally occurring ster... more Nanoelectrospray ionization (nanoESI) mass spectrometry was performed on naturally occurring steroid sulfates and unconjugated steroids derivatized to their sulfate esters using precursor ion monitoring. Initially, an extraction method was developed based on a combinatorial approach employed to obtain the most efficient liquid/liquid extraction protocol. The new method allowed unconjugated steroids and their sulfated analogues to be isolated separately in a two-step procedure using diethyl ether/hexane (90:10, v/v) in the first step to extract the unconjugated steroids and chloroform/2-butanol (50:50, v/v) in the second step to extract steroid sulfates. Precursor ion scanning performed with a triple-quadrupole mass spectrometer was used to examine quantitatively the extracted unconjugated and sulfated steroids, where the recovery efficiency averaged 70 and 87%, respectively. In addition, some steroids could be structurally elucidated by employing tandem mass spectrometry. The limit of detection for steroid sulfates from the biological matrix was 200 amol/microL (approximately 80 fg/microL) with only 1 microL of sample being injected. Endogenous levels of the unconjugated and sulfated steroids were detected and quantified from physiological samples including urine and blood. Internal standards, pregnenolone-d4 sulfate and dehydroepiandrosterone-d2 (DHEA), were used for quantitation. Extraction and nanoESI analyses were also performed on cerebrospinal fluid where the neurosteroid DHEA sulfate was detected. The small amount of material consumed (typically less than 20% of the injection volume) suggests that nanoESI has even greater potential for high sensitivity when combined with nanoLC approaches, especially for monitoring reproductive and adrenal steroids, as well as for the analysis of the less abundant neurosteroids.

Virology, Jan 15, 2003

Quantitative enzyme accessibility experiments using nano liquid chromatography electrospray mass ... more Quantitative enzyme accessibility experiments using nano liquid chromatography electrospray mass spectrometry combined with limited proteolysis and isotope-labeling was used to examine the dynamic nature of the human rhinovirus (HRV) capsid in the presence of three antiviral compounds, a neutralizing Fab, and drug binding cavity mutations. Using these methods, it was found that the antivirals WIN 52084 and picovir (pleconaril) stabilized the capsid, while dansylaziridine caused destabilization. Site-directed mutations in the drug-binding cavity were found to stabilize the HRV14 capsid against proteolytic digestion in a manner similar to WIN 52084 and pleconaril. Antibodies that bind to the NIm-IA antigenic site and penetrate the canyon were also observed to protect the virion against proteolytic cleavage. These results demonstrate that quantifying the effects of antiviral ligands on protein "breathing" can be used to compare their mode of action and efficacy. In this case,...

Scientific Reports, 2011

Diabetic retinopathy is the leading cause of visual loss in individuals under the age of 55. Umbi... more Diabetic retinopathy is the leading cause of visual loss in individuals under the age of 55. Umbilical cord blood (UCB)-derived myeloid progenitor cells have been shown to decrease neuronal damage associated with ischemia in the central nervous system. In this study we show that UCB-derived CD14 1 progenitor cells provide rescue effects in a mouse model of ischemic retinopathy by promoting physiological angiogenesis and reducing associated inflammation. We use confocal microscopy to trace the fate of injected human UCB-derived CD14 1 cells and PCR with species-specific probes to investigate their gene expression profile before and after injection. Metabolomic analysis measures changes induced by CD14 1 cells. Our results demonstrate that human cells differentiate in vivo into M2 macrophages and induce the polarization of resident M2 macrophages. This leads to stabilization of the ischemia-injured retinal vasculature by modulating the inflammatory response, reducing oxidative stress and apoptosis and promoting tissue repair. SUBJECT AREAS: ANGIOGENESIS VASCULAR BIOLOGY STEM CELLS METABOLOMICS