DOCSLIB.ORG

Biomarkers in Pharmacology and Drug Discovery

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Biomarkers in Pharmacology and Drug Discovery Biochemical Pharmacology 87 (2014) 172–188 Contents lists available at ScienceDirect Biochemical Pharmacology jo urnal homepage: www.elsevier.com/locate/biochempharm Review – Part of the Special Issue – Pharmacology in 21st Century Biomedical Research Biomarkers in pharmacology and drug discovery a, a,b D.C. Anderson *, Krishna Kodukula a Center for Advanced Drug Research, SRI International, Harrisonburg, VA 22802, USA b Departments of Biology, and Chemistry and Biochemistry, James Madison University, Harrisonburg, VA 22802, USA A R T I C L E I N F O A B S T R A C T Article history: Biomarkers, quantitatively measurable indicators of biological or pathogenic processes, once validated Received 16 August 2013 play a critical role in disease diagnostics, the prediction of disease progression, and/or monitoring of the Accepted 19 August 2013 response to treatment. They may also represent drug targets. A number of different methods can be used Available online 31 August 2013 for biomarker discovery and validation, including proteomics methods, metabolomics, imaging, and genome wide association studies (GWASs) and can be analysed using receiver operating characteristic Keywords: (ROC) plots. The relative utility of single biomarkers compared to biomarker panels is discussed, along Biomarkers with paradigms for biomarker development, the latter in the context of three large-scale biomarker Disease diagnosis biomarker discovery consortia, the Critical Path Predictive Safety Testing Consortium (PSTC), the NCI Early Detection Research Polypharmacy Network (EDRN) and the Alzheimer’s Disease Neuroimaging Initiative (ADNI). The importance of Protein biomarkers systematic optimization of many parameters in biomarker analysis, including validation, reproducibili- ty, study design, statistical analysis and avoidance of bias are critical features used by these consortia. Problems including introduction of bias into study designs, data reporting or data analysis are also reviewed. ß 2013 Elsevier Inc. All rights reserved. Contents 1. Introduction . 173 2. Defining biomarkers . 173 2.1. Drug targets and biomarkers . 174 2.2. Polypharmacy . 174 3. Biomarker discovery . 175 3.1. Targeted methods . 175 3.2. Non-targeted methods . 176 3.2.1. Proteomics: 2D LC/MS/MS. 176 3.2.2. Proteomics: SELDI-TOF, MALDI protein profiling . 176 3.2.3. Metabolomics . 176 3.2.4. Imaging . 177 3.2.5. Mass spectrometry imaging . 177 3.2.6. Genome wide association studies (GWASs) . 178 4. Approaches to analysis . 178 4.1. A single biomarker versus a biomarker panel . 179 5. Biomarker qualification and subsequent development . 180 5.1. Predictive Safety Testing Consortium (PSTC). 180 5.2. Early Detection Research Network (EDRN) . 180 5.3. Alzheimer’s Disease Neuroimaging Initiative (ADNI) . 181 6. Biomarker validation . 181 7. Challenges . 182 7.1. Most published biomarker candidates do not enter clinical practice. 182 7.2. Problems with selection of preclinical samples. 182 7.3. Sample storage and handling . 182 * Corresponding author. E-mail address: [email protected] (D.C. Anderson). 0006-2952/$ – see front matter ß 2013 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.bcp.2013.08.026 D.C. Anderson, K. Kodukula / Biochemical Pharmacology 87 (2014) 172–188 173 7.4. Pooling samples . 182 7.5. Biomarker dynamic range . 182 7.6. Data analysis and bias . 183 7.6.1. Batch effects. 183 7.6.2. Selective data reporting, incomplete validation and forensic bioinformatics . 183 7.7. Study design . 183 8. Conclusions . 183 Acknowledgements . 183 References . 183 1. Introduction of the drug discovery process; characterization of animal disease models; use in clinical trials to stratify patients; use as diagnostics Biomarkers, where these exist and have been appropriately or companion diagnostics; or as indicators of therapeutic validated [1–7] can play a critical role in biomedical research, drug response. discovery and development, including: Biomarkers, broadly defined, can be a variety of (ideally) quantitatively measured indicators of biological or pathphysiolo- Their use as diagnostics to establish the presence of a disease. gical processes, or the response to therapeutic intervention, predicting disease progression and the stratification of disease including molecular entities, images or other measured activities severity. or properties, or their combination as a biomarker panel. They assessing and predicting the clinical benefit(s) or toxicity include proteins, protein modifications, or activities, e.g., enzymes resulting from a therapeutic intervention. [12]. DNA-based biomarkers include DNA (e.g., circulating DNA can monitoring treatment response, including target engagement be used to diagnose genetic diseases such as Down’s Syndrome in where appropriate. unborn children [13]), single nucleotide polymorphisms (SNPs), gene copy number variations (CNVs; DNA insertions, deletions, Biomarkers can be used as part of a personalized medicine rearrangements such as inversions and translocations larger than paradigm to customize treatment to the specific disease char- 1 kb, and insertions/deletions less than 1 kb [14]), mRNA or long acteristics of an individual patient. They can also be used to better non-coding RNA [15]. Epigenetic biomarkers include methylated understand disease mechanisms and to identify novel disease DNA (e.g., fecal DNA tests for detection of colorectal cancer [16]), targets. microRNA (e.g., a microRNA panel for diagnosis of stage II-IV colon Issues that are addressed in this review include: (i) cancer [17]), or modified histones. Other more traditional biomarker discovery, development and analysis that requires biomarkers include gross phenotypes such as blood pressure, a combination of careful study design to avoid distorting or lung volume, blood sugar and urine volume, cellular metabolites or negating results due to bias; (ii) systematic development of lipids and other physical measurements including structural (e.g., assays; (iii) larger scale collaborations involving multiple computed tomography or magnetic resonance) or functional (e.g., patient populations to develop and refine robust and reproduc- positron emission tomography) images as used in neuroimaging ible assays and; (iv) for clinical validation [1–7], transparent [18], or electroencephalograms [19]. Combinations of different data analysis (particularly when large datasets are involved), biomarker types (e.g., fluid biomarkers, tissue images, allele with statistical analyses.
Load more

Recommended publications
  • The Arctic Sea Ice Biomarker IP25: a Review of Current Understanding, Recommendations for Future Research and Applications in Palaeo Sea Ice Reconstructions
    Quaternary Science Reviews 79 (2013) 9e25 Contents lists available at SciVerse ScienceDirect Quaternary Science Reviews journal homepage: www.elsevier.com/locate/quascirev The Arctic sea ice biomarker IP25: a review of current understanding, recommendations for future research and applications in palaeo sea ice reconstructions Simon T. Belt a,*, Juliane Müller b a Biogeochemistry Research Centre, School of Geography, Earth and Environmental Sciences, Plymouth University, Plymouth PL4 8AA, UK b Alfred Wegener Institute for Polar and Marine Research, 27568 Bremerhaven, Germany article info abstract Article history: In recent years, a novel proxy for the past occurrence of Arctic sea ice has been proposed that is based Received 18 June 2012 on the variable marine sedimentary abundance of an organic geochemical lipid derived from sea ice Received in revised form diatoms in the spring. This lipid, termed IP25 (Ice Proxy with 25 carbon atoms), is a highly branched 29 November 2012 isoprenoid mono-unsaturated alkene that appears to be sufficiently stable in sediments to permit Accepted 4 December 2012 meaningful palaeo sea ice reconstructions to be carried out over short- to long-term timescales. Since Available online 17 January 2013 the first proposed use of IP25 as a proxy for palaeo sea ice by Belt et al. (2007), a number of laboratories have measured this biomarker in Arctic sediments and it is anticipated that research activity in this area Keywords: Sea ice will increase further in the future. The content of this review is divided into a number of sections. fi Arctic Firstly, we describe the scienti c basis for the IP25 proxy and its initial discovery in Arctic sea ice, Proxy sedimenting particles and sediments.
    [Show full text]
  • Technical Considerations and Protocol Optimization for Neonatal Salivary Biomarker Discovery and Analysis
    PERSPECTIVE published: 26 January 2021 doi: 10.3389/fped.2020.618553 Technical Considerations and Protocol Optimization for Neonatal Salivary Biomarker Discovery and Analysis Elizabeth Yen 1,2, Tomoko Kaneko-Tarui 1 and Jill L. Maron 1,2* 1 Mother Infant Research Institute at Tufts Medical Center, Boston, MA, United States, 2 Division of Newborn Medicine, Tufts Children’s Hospital, Boston, MA, United States Non-invasive techniques to monitor and diagnose neonates, particularly those born prematurely, are a long-sought out goal of Newborn Medicine. In recent years, technical advances, combined with increased assay sensitivity, have permitted the high-throughput analysis of multiple biomarkers simultaneously from a single sample source. Multiplexed transcriptomic and proteomic platforms, along with more comprehensive assays such as RNASeq, allow for interrogation of ongoing physiology and pathology in unprecedented ways. In the fragile neonatal population, saliva is an ideal biofluid to assess clinical status serially and offers many advantages over more Edited by: invasively obtained blood samples. Importantly, saliva samples are amenable to analysis Diego Gazzolo, SS Annunziata Polyclinic Hospital, on emerging proteomic and transcriptomic platforms, even at quantitatively limited Chieti, Italy volumes. However, biomarker targets are often degraded in human saliva, and as a mixed Reviewed by: source biofluid containing both human and microbial targets, saliva presents unique Anne Lee Solevåg, challenges for the investigator. Here, we provide insight into technical considerations Akershus University Hospital, Norway Trent E. Tipple, and protocol optimizations developed in our laboratory to quantify and discover neonatal University of Oklahoma Health salivary biomarkers with improved reproducibility and reliability. We will detail insights Sciences Center, United States learned from years of experimentation on neonatal saliva within our laboratory ranging *Correspondence: Jill L.
    [Show full text]
  • Exploring the Transcriptome for Novel Biomarker Discovery AMP-AD Biomarker Pilot Study
    Exploring the transcriptome for novel biomarker discovery AMP-AD Biomarker Pilot Study Nilüfer Ertekin-Taner, MD, PhD Professor of Neurology and Neuroscience Mayo Clinic Florida Spring ADC Meeting May 2nd, 2019 ©2016 MFMER | slide-1 AMP-AD Team Mayo Clinic Florida Banner Sun Health Nilüfer Ertekin Taner, MD, PhD Tom Beach, MD Steven G. Younkin, MD, PhD Dennis Dickson, MD New York Genomics Center (WGS) Minerva Carrasquillo, PhD Mariet Allen, PhD Mayo Clinic Genomics Core Joseph Reddy, PhD Bruce Eckloff (RNASeq) Xue Wang, PhD Julie Cunningham, PhD (GWAS) Kim Malphrus Thuy Nguyen Mayo Clinic Bioinformatics Core Sarah Lincoln Asha Nair, PhD University of Florida Mayo Clinic Epigenomics Development Todd Golde, MD, PhD. Laboratory Jada Lewis, Ph.D. Tamas Ordog, MD Paramita Chakrabarty, PhD Jeong-Hong Lee, PhD Yona Levites, PhD Mayo Clinic IT Institute for Systems Biology Andy Cook Nathan Price, PhD Curt Younkin Cory Funk, PhD Hongdong Li, PhD Mayo Clinic Study of Aging Paul Shannon Ronald Petersen, MD, PhD *AMP-AD consortium* ©2016 MFMER | slide-2 Overarching Goal A System Approach to Targeting Innate Immunity in AD (U01 AG046193) To identify and validate targets within innate immune signaling, and other pathways that can provide disease- modifying effects in AD using a multifaceted systems level approach. ©2016 MFMER | slide-3 AMP-AD Phase I Original Aim 1: To detect Original Aim 2: To assess AD Original Aim 3: To Original Aim 4: To transcript alterations in innate risk conferred by variants in manipulate innate determine outcome of immunity genes in mice and innate immunity genes from immune states in gene manipulation in humans.
    [Show full text]
  • Emerging Role and Recent Applications of Metabolomics Biomarkers in Obesity Disease Cite This: RSC Adv.,2017,7, 14966 Research
    RSC Advances View Article Online REVIEW View Journal | View Issue Emerging role and recent applications of metabolomics biomarkers in obesity disease Cite this: RSC Adv.,2017,7, 14966 research Aihua Zhang,a Hui Suna and Xijun Wang*ab Metabolomics is a promising approach for the identification of metabolites which serve for early diagnosis, prediction of therapeutic response and prognosis of disease. Obesity is becoming a major health concern in the world. The mechanisms underlying obesity have not been well characterized; obviously, more sensitive biomarkers for obesity diseases are urgently needed. Fortunately, metabolomics – the systematic study of metabolites, which are small molecules generated by the process of metabolism – has been important in elucidating the pathways underlying obesity-associated co-morbidities. The endogenous metabolites have key roles in biological systems and represent attractive candidates to understand obesity phenotypes. Novel metabolite markers are crucial to develop diagnostics for obesity related metabolic disorders. Received 26th December 2016 Creative Commons Attribution 3.0 Unported Licence. Metabolomics allows unparalleled opportunities to seize the molecular mechanisms of obesity and Accepted 28th February 2017 obesity-related diseases. In this review, we discuss the current state of metabolomic analysis of obesity DOI: 10.1039/c6ra28715h diseases, and also highlight the potential role of key metabolites in assessing obesity disease and explore rsc.li/rsc-advances the interrelated pathways. 1. Introduction
    [Show full text]
  • Computational Approaches for Drug Design and Discovery: an Overview
    Review Article Computational Approaches for Drug Design and Discovery: An Overview Baldi A College of Pharmacy, Dr. Shri R.M.S. Institute of Science & Technology, Bhanpura, Dist. Mandsaur (M.P.), India ARTICLE INFO ABSTRACT Article history: The process of drug discovery is very complex and requires an interdisciplinary effort to design Received 12 July 2009 effective and commercially feasible drugs. The objective of drug design is to find a chemical Accepted 21 July 2009 compound that can fit to a specific cavity on a protein target both geometrically and chemically. Available online 04 February 2010 After passing the animal tests and human clinical trials, this compound becomes a drug available Keywords: to patients. The conventional drug design methods include random screening of chemicals Computer-aided drug design found in nature or synthesized in laboratories. The problems with this method are long design Combinatorial chemistry cycle and high cost. Modern approach including structure-based drug design with the help Drug of informatic technologies and computational methods has speeded up the drug discovery Structure-based drug deign process in an efficient manner. Remarkable progress has been made during the past five years in almost all the areas concerned with drug design and discovery. An improved generation of softwares with easy operation and superior computational tools to generate chemically stable and worthy compounds with refinement capability has been developed. These tools can tap into cheminformation to shorten the cycle of drug discovery, and thus make drug discovery more cost-effective. A complete overview of drug discovery process with comparison of conventional approaches of drug discovery is discussed here.
    [Show full text]
  • Opportunities and Challenges in Phenotypic Drug Discovery: an Industry Perspective
    PERSPECTIVES Nevertheless, there are still challenges in OPINION prospectively understanding the key success factors for modern PDD and how maximal Opportunities and challenges in value can be obtained. Articles published after the analysis by Swinney and Anthony have re-examined the contribution of PDD phenotypic drug discovery: an to new drug discovery6,7 and have refined the conditions for its successful application8. industry perspective Importantly, it is apparent on closer examination that the classification of drugs John G. Moffat, Fabien Vincent, Jonathan A. Lee, Jörg Eder and as ‘phenotypically discovered’ is somewhat Marco Prunotto inconsistent6,7 and that, in fact, the majority of successful drug discovery programmes Abstract | Phenotypic drug discovery (PDD) approaches do not rely on knowledge combine target knowledge and functional of the identity of a specific drug target or a hypothesis about its role in disease, in cellular assays to identify drug candidates contrast to the target-based strategies that have been widely used in the with the most advantageous molecular pharmaceutical industry in the past three decades. However, in recent years, there mechanism of action (MoA). Although there is clear evidence that phenotypic has been a resurgence in interest in PDD approaches based on their potential to screening can be an attractive proposition address the incompletely understood complexity of diseases and their promise for efficiently identifying functionally of delivering first-in-class drugs, as well as major advances in the tools for active hits that lead to first-in-class drugs, cell-based phenotypic screening. Nevertheless, PDD approaches also have the gap between a screening hit and an considerable challenges, such as hit validation and target deconvolution.
    [Show full text]
  • Medicinal Chemistry for Drug Discovery | Charles River
    Summary Medicinal chemistry is an integral part of bringing a drug through development. Our medicinal chemistry approach enables clients to benefit from efficient navigation of the early drug discovery process through to delivery of preclinical candidates. DISCOVERY Click to learn more Medicinal Chemistry for Drug Discovery Medicinal Chemistry A Proven Track Record in Drug Discovery Services: Our medicinal chemistry team has experience in progressing small molecule drug discovery programs across a broad range • Target identification of therapeutic areas and gene families. Our scientists are skilled in the design and synthesis of novel pharmacologically active - Capture Compound® mass compounds and understand the challenges facing modern drug discovery. Together, they are cited as inventors on over spectrometry (CCMS) 350 patents and have identified 80 preclinical candidates for client organizations across a variety of therapeutic areas. As • Hit-finding strategies project leaders, our chemists are fundamental in driving the program strategy and have consistently empowered our clients’ - Optimizing high-throughput success. A high proportion of candidates regularly progress to the clinic, and our first co-invented drug, Belinostat, received screening (HTS) hits marketing approval in 2015. As an organization, Charles River has worked on 85% of the therapies approved in 2018. • Hit-to-lead We have a deep understanding of the factors that drive medicinal chemistry design: structure-activity relationship (SAR), • Lead optimization biology, physical chemistry, drug metabolism and pharmacokinetics (DMPK), pharmacokinetic/pharmacodynamic (PK/PD) • Patent strategy modelling, and in vivo efficacy. Charles River scientists are skilled in structure-based and ligand-based design approaches • Preparation for IND filing utilizing our in-house computer-aided drug design (CADD) expertise.
    [Show full text]
  • Apply Proteomic Approaches to Biomarker Discovery Proteomics for Biomarker Discovery
    Apply Proteomic Approaches to Biomarker Discovery Proteomics for Biomarker Discovery Why is it important to discover biomarkers? Biomarkers are biological substances that can be measured and quantified as indicators for objective assessment of physiological processes, therapeutic outcomes, environmental exposure, or pharmacologic responses to a certain drug. Biomarker discovery has many excellent outcomes: ◆ Provides specific information about the ◆ Allows clinicians to predict or monitor presence of a certain disease or disease stage. drug efficacy. ◆ Allows researchers to evaluate the safety or ◆ Confirms a drug’s pharmacological or efficacy of a particular drug in development. biological mechanism of action and helps minimize the safety risks. Figure 1. Potential use of biomarkers. Proteomics in biomarker discovery Typical molecular biomarkers include proteins, genetic mutations, aberrant methylation patterns, abnormal transcripts, miRNAs, and other biological molecules. Protein biomarkers are considered to be reliable indicators of the disease state and clinical outcome as they are the endpoint of biological processes. Remarkable innovations in proteomic technologies in the last years have greatly accelerated the process of biomarker discovery. 45-1 Ramsey Road, Shirley, NY 11967, USA www.creative-proteomics.com Tel: 1-631-275-3058 Fax: 1-631-614-7828 Email: [email protected] Proteomics for Biomarker Discovery ◆ Proteomes and proteomics Proteomes represent the network of interactions between genetic background and environmental factors. They may be considered as molecular signatures of disease, involving small circulating proteins or peptide chains from degraded molecules in various disease states. Proteomics is the study of the proteome including protein identification and quantification, and detection of protein-protein or protein-nucleic acid interactions, and post-translational modifications.
    [Show full text]
  • Overcoming the Immunosuppressive Tumor Microenvironment in Multiple Myeloma
    cancers Review Overcoming the Immunosuppressive Tumor Microenvironment in Multiple Myeloma Fatih M. Uckun 1,2,3 1 Norris Comprehensive Cancer Center and Childrens Center for Cancer and Blood Diseases, University of Southern California Keck School of Medicine (USC KSOM), Los Angeles, CA 90027, USA; [email protected] 2 Department of Developmental Therapeutics, Immunology, and Integrative Medicine, Drug Discovery Institute, Ares Pharmaceuticals, St. Paul, MN 55110, USA 3 Reven Pharmaceuticals, Translational Oncology Program, Golden, CO 80401, USA Simple Summary: This article provides a comprehensive review of new and emerging treatment strategies against multiple myeloma that employ precision medicines and/or drugs capable of improving the ability of the immune system to prevent or slow down the progression of multiple myeloma. These rationally designed new treatment methods have the potential to change the therapeutic landscape in multiple myeloma and improve the long-term survival outcome. Abstract: SeverFigurel cellular elements of the bone marrow (BM) microenvironment in multiple myeloma (MM) patients contribute to the immune evasion, proliferation, and drug resistance of MM cells, including myeloid-derived suppressor cells (MDSCs), tumor-associated M2-like, “alter- natively activated” macrophages, CD38+ regulatory B-cells (Bregs), and regulatory T-cells (Tregs). These immunosuppressive elements in bidirectional and multi-directional crosstalk with each other inhibit both memory and cytotoxic effector T-cell populations as well as natural killer (NK) cells. Immunomodulatory imide drugs (IMiDs), protease inhibitors (PI), monoclonal antibodies (MoAb), Citation: Uckun, F.M. Overcoming the Immunosuppressive Tumor adoptive T-cell/NK cell therapy, and inhibitors of anti-apoptotic signaling pathways have emerged as Microenvironment in Multiple promising therapeutic platforms that can be employed in various combinations as part of a rationally Myeloma.
    [Show full text]
  • Drug Discovery - Yesterday and Tomorrow: the Common Approaches in Drug Design and Cancer
    Cell & Cellular Life Sciences Journal Drug Discovery - Yesterday and Tomorrow: The Common Approaches in Drug Design and Cancer 1,2 1 3 Hamad ON *, Amran SIB and Sabbah AM Mini Review 1Faculty of Bioscience & Medical Engineering, Malaysia Volume 3 Issue 1 2University of Wasit, College of Medicine, Iraq Received Date: February 27, 2018 3Forensic DNA for research and training Centre, Al Nahrain University, Iraq Published Date: April 03, 2018 *Corresponding author: Oras Naji Hamad, Faculty of Bioscience & Medical Engineering, University of Technology, Malaysia, Tel: 01121715960; E-mail: [email protected] Abstract The process of drug discovery has undergone radical changes and development over years. Traditionally, the drugs were discovered by employing chemistry and pharmacology-based cautious approach. When natural products were the most important source of drugs or drug precursors, but the conventional randomized drug research phenomenon was no longer effective at that time due to many negatives of these approaches like: high expenses of discovering new drugs, time-consuming and reduced success guarantee. Thus, with the development of the era, the concept of “Rational Drug Design” has enabled drug target identification and validation to be more specific. In addition, several novel technologies and approaches have been introducing economics, proteomics and other omics areas such as 3D QSAR, pharmacophore modeling and other, which playing a promising role in accelerating the pace of drug discovery process. Their view of the current
    [Show full text]
  • The Biotech/Pharma Perspective
    Biomarkers – The Biotech/Pharma perspective R&D manager - Kim Holmstrøm Bioneer What are Biomarkers? § The modern definition was proposed at the US National Institutes of Health workshop in 1998: “A biomarker is a characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes or pharmacological responses to a therapeutic intervention.” 2 What are Biomarkers? Classical Molecular markers • Body temperature § Proteins (e.g. antibodies, • Blood pressure membrane receptors) • Heart rate, etc. § Hormones (e.g. peptide hormones, steroid hormones) • Imaging (MR, PET) § Carbohydrates (e.g. glucose) § Nucleic acids (DNA, mRNA, ncRNA) § Epigenetic factors (methylation, histone modifications) § Lipids (e.g. cholesterol) § Metabolites Biomarkers in human disease and drug development § Diagnostic - Determines the type of disease § Predictive - Identification of subpopulations of patients most likely to respond to a given treatment § Prognostic - Provides information of the likely course of e.g. a cancer disease § Mechanistic - Provides infomation on e.g. specific cell signaling mechanisms that are affected by a drug § Safety - Indicates toxicity effects 4 Genome for science, for health, for individuals Your genome First human genome 1000 Genome 50 Danish families Personal genomes! sequencing Project 150 genomes in total for everyone 1990-2002 2009-2012 The Danish reference (2015-2025) genome The human ! Human genome Healthy lifestyle “building blocks” variation 2011-2015 Prevention of
    [Show full text]
  • Metabolomics to Provide Biomarkers and Mechanistic Insights
    RTI International Metabolomics to Provide Biomarkers and Mechanistic Insights Susan Sumner, PhD Director NIH Eastern Regional Comprehensive Metabolomics Resource Core Systems and Translational Sciences Program RTI International [email protected] www.rti.org\rcmrc 919-541-7479 RTI International is a trade name of Research Triangle Institute. www.rti.org RTI International About RTI International . RTI is an independent not-for-profit research institute established in 1958 in Research Triangle Park, NC. RTI’s mission is to improve the human condition by turning knowledge into practice. RTI has 9 offices in the United States, 8 offices worldwide, and has projects in more than 40 countries. RTI is staffed with more than 4,000 employees working in health and pharmaceuticals, laboratory and chemistry services, advanced technology, statistics, international development, energy and the environment, education and training, and surveys. RTI has more than 800,000 square feet (ft2) of laboratory and office facilities in RTP, NC. The metabolomics facility in the Research Triangle Park consists of ~22,000 ft2 laboratory space. RTI International Metabolomics . Metabolomics involves the broad spectrum analysis of the low molecular weight complement of cells, tissues, or biological fluids. Metabolomics makes it feasible to uniquely profile the biochemistry of an individual, or system, apart from, or in addition to, the genome. – Metabon(l)omics is used to determine the pattern of changes (and related metabolites) arising from disease, dysfunction, disorder, or from the therapeutic or adverse effects of xenobiotics; including applications in plant and mammalian studies. This leading-edge method is now coming to the fore to reveal biomarkers for the early detection and diagnosis of disease, to monitor therapeutic treatments, and to provide insights into biological mechanisms.
    [Show full text]