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James Inglese

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  • Comment: Provide secondary sources viz. newspapers, news coverages and/or books that cover the subject in detail. Journal Articles and papers authored by this person can’t alone be used as sources for having a stand-alone article about him on Wikipedia. Dial911 (talk) 00:03, 31 January 2018 (UTC)
James Inglese

James Inglese is an American biochemist and a leader in the area of small molecule high throughput screening.

James Inglese is the director of the Assay Development and Screening Technology laboratory at the National Center for Advancing Translational Sciences, a Center within the National Institutes of Health.

Inglese’s laboratory develops methods and strategies in molecular pharmacology with drug discovery applications. The work of his research group and collaborators focus on genetic and infectious disease-associated biology. Many of the efforts aimed at genetic disorders are in partnership with rare disease foundations (see External links).

Dr. Inglese received his BS in Chemistry from the Rensselaer Polytechnic Institute in 1984 and a PhD in Organic Chemistry from the Pennsylvania State University in 1989, where he conducted research with Professor Stephen J. Benkovic on inhibitor design, synthesis and mechanism studies for the reduced folate-requiring enzymes (e.g. phosphoribosylglycinamide formyltransferase) of purine biosynthesis.[1]. He went on to pursue postdoctoral studies on G protein-coupled receptors (GPCRs) with Professor Robert J. Lefkowitz at the Duke University School of Medicine. During this time Dr. Inglese studied the emerging family of G protein-coupled receptor kinases (GRKs), discovering several lipid post-translational modifications regulating GRK function and GPCR interaction [2]. Defective isoprenylation of the visual GRK, rhodopsin kinase may have a basis in certain forms of hereditary blindness.

Over the following 10 year period, Dr. Inglese led research groups in the private sector. At the combinatorial chemistry biotech, Pharmacopeia Inc., he developed methods to enable the company's electrophoretic tag-encoded libraries, pioneering the development of technologies such as microplate laser scanning cytometry for high throughput screening (HTS) [3]. Subsequently, at the Merck Research Laboratories, he directed HTS assay development for the analysis of chemical libraries in the company’s drug discovery efforts.

Dr. Inglese co-founded the NIH’s Chemical Genomics Center (NCGC) in 2004. This came at time when the academic community was divided with regard to the role of academics in drug development with many thinking that this should be solely the domain of the pharmaceutical industry. Dr. Inglese played a major role in bringing new technology and methods to drug development within the NIH [4]. As Deputy Director of the NCGC, Dr. Inglese led the development of the Center’s Quantitative High Throughput Screening (qHTS) platform [5][6][7]. This 2006 publication pioneered the advent of this new approach to HTS that normally relies on a single concentration of a test compound [8] and has been cited over 500 times according to Scopus and Web of Science. Dr. Inglese has overseen the use of qHTS in numerous collaborative chemical probe discovery projects with Investigators from academia [9]. According to Scopus, as of February 2020, Dr. Inglese has published 180 documents that have been cited over 12,000 times. Fifteen publications have been cited more than 200 times, while 35 have been cited 100 times or more [10].

In 2009, Dr. Inglese and his team ignited controversy when their mechanistic studies of PTC124 (Ataluren), at the time in clinical trials for subclasses of cystic fibrosis and muscular dystrophy, revealed that the precursor discovery and subsequent development may have been guided by a confounding artifact of the reporter gene assay used in its identification and medicinal chemistry optimization [11][12]. The broader implications of this work led Inglese to design a new class of HTS reporter using the concept from physics of a coincidence circuit to avoid such pitfalls [13]. By joining two biochemically-distinct reporters, separated by a P2A ribosome skipping site, one can distinguish between compounds that act at the level of reporter expression, which will affect both reporters, from compounds that directly affect the activity of one or the other reporter.

Complementing the laboratory’s bioassay program, Dr. Inglese explores screening strategies to assess pharmacological activity, for example, from secondary metabolites contained in natural product extracts[14] or novel chemical scaffolds derived from synthetic chemistry methodology research [15]. His team’s recent efforts have explored topologically expansive mRNA-encoded peptide libraries using a modified mRNA display to identify inhibitors of infectious disease molecular targets that have presented challenges to conventional chemical library HTS [16][17]

File:James Inglese and Francis Collins at SLAS2015 meeting.jpg
Dr. James Inglese presenting an award to NIH Director Dr. Francis Collins at SLAS2015

In addition to his many research contributions, Dr. Inglese founded the journal ASSAY and Drug Development Technologies, serving as Editor-in-Chief from 2002 to 2014, and was Editor-in-Chief of the Methods in Enzymology volume 414 on Measuring Biological Responses with Automated Microscopy [18] In addition, Dr. Inglese serves or has served on the Scientific Advisory Boards for the publications Genetic Engineering & Biotechnology News [19] and the American Chemical Society journal ACS Central Science[20]. He has also served as an Expert for the American Chemical Society Chemical Biology's online Ask the Expert feature. [21] Dr. Inglese has chaired and co-chaired various scientific conferences including the 2015 conference of the Society of Laboratory Automation and Screening (SLAS 2015).

References

  1. ^ Inglese, J.; Blatchly, R.A.; Benkovic, S.J. (1989). "A Multisubstrate Adduct Inhibitor of a Purine Biosynthetic Enzyme with a Picomolar Dissociation Constant". J. Med. Chem. 32: 937–940. PMID 2709379.
  2. ^ Inglese, J.; Glickman, J.F.; Lorenz, W.; Caron, M.G.; Lefkowitz, R.J. (1992). "Isoprenylation of a Protein Kinase: Farnesylation / α-Carboxyl Methylation Required for Full Enzymatic Activity of Rhodopsin Kinase". J. Biol. Chem. 267: 1422–1425. PMID 1730692. {{cite journal}}: Cite has empty unknown parameter: |1= (help)
  3. ^ Zuck, P.; Lao, Z.; Skwish, S.; Glickman, J.F.; Yang, K.; Burbaum, J.; Inglese, J. (1999). "Ligand-receptor binding measured by laser-scanning imaging". Proc. Nat’l Acad. Sci. USA. 96 (20): 11122–11127. doi:10.1073/pnas.96.20.11122. PMID 10500140.
  4. ^ https://www.sciencemag.org/features/2008/03/drug-discovery-and-development-complex-team-sport
  5. ^ https://cen.acs.org/articles/84/web/2006/07/High-Throughput-Screening-Multiple-Concentrations.html
  6. ^ https://cen.acs.org/articles/84/i31/Screening-made-easier.html
  7. ^ Inglese, J.; Auld, D.S.; Jadhav, A.; Johnson, R.L.; Simeonov, A.; Yasgar, A.; Zheng, W.; Austin, C.P. (2006). "Quantitative High-Throughput Screening (qHTS): A Titration-based Approach that Efficiently Identifies Biological Activities in Large Chemical Libraries". Proc. Nat’l Acad. Sci. USA. 103 (31): 11473–11478. doi:10.1073/pnas.0604348103. PMID 16864780.
  8. ^ Shockley, K.R.; Gupta, S.; Harris, S.F.; Lahiri, S.N.; Peddada, S.D. (2019). "Quality Control of Quantitative High Throughput Screening Data". Front. Genet. 10: 387. doi:10.3389/fgene.2019.00387.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  9. ^ https://cen.acs.org/articles/88/i7/Slaying-Cancer-Roots.html
  10. ^ https://www.scopus.com/authid/detail.uri?authorId=26031365900
  11. ^ Sheridan, C. (2013). "Doubts raised over 'read-through' Duchenne drug mechanism". Nature Biotechnology. 31 (9): :771-773. doi:10.1038/nbt0913-771. PMID 24022133.
  12. ^ Auld, D.S.; Lovell, S.; Thorne, N.; Lea, W.A.; Maloney, D.J.; v; Rai, G.; Battaile, K.P.; Thomas, C.J.; Simeonov, A.; Hanzlik, R.P.; Inglese, J. (2010). "Molecular basis for the high-affinity binding and stabilization of firefly luciferase by PTC124". Proc. Nat’l Acad. Sci. USA. 107 (11): 4878–4883. doi:10.1073/pnas.0909141107. PMID 20194791.
  13. ^ Cheng, K.C.; Inglese, J. (2012). "A coincidence reporter-gene system for high throughput screening". Nature Methods. 9: 937. doi:10.1038/nmeth.2170. PMID 23018994.
  14. ^ Cheng, K.C.; Cao, S.; Raveh, A.; MacArthur, R.; Dranchak, P.; Chlipala, G.; Okoneski, M.T.; Guha, R.; Eastman, R.T.; Yuan, J.; Schultz, P.J.; Su, X.,Z.; Tamayo-Castillo, G.; Matainaho, T.; Clardy, J.; Sherman, D.H.; Inglese, J. (2015). "Actinoramide A identified as a potent antimalarial from titration-based screening of marine natural product extracts". Natural Products. 78 (10): 2411–2422. doi:10.1021/acs.jnatprod.5b00489. PMID 26465675.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  15. ^ Brown, L.E.; Cheng, K.C.; Wei, W.G.; Yuan, P.; Dai, P.; Trilles, R.; Ni, F.; Yuan, J.; MacArthur, R.; Guha, R.; Johnson, R.L.; Su, X.,Z.; Dominguez, M.M.; Snyder, J.K.; Beeler, A.B.; Schaus, S.E.; Inglese, J.; Porco, J.A. Jr. (2011). "Discovery of New Anti-Malarial Chemotypes through Chemical Methodology and Library Development". Proc. Nat’l Acad. Sci. USA. 108 (17): 6775–6780. doi:10.1073/pnas.1017666108. PMID 21498685.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  16. ^ https://directorsblog.nih.gov/2017/04/11/fighting-parasitic-infections-promise-in-cyclic-peptides/
  17. ^ https://www.nih.gov/news-events/news-releases/international-scientific-teams-find-potential-approach-against-parasites
  18. ^ https://www.elsevier.com/books/measuring-biological-responses-with-automated-microscopy/inglese/978-0-12-182819-6
  19. ^ https://www.genengnews.com/advisory-board/
  20. ^ https://pubs.acs.org/userimages/ContentEditor/1417558152594/acscii_eab.pdf
  21. ^ Brownlee, C. (2008). "James Inglese: Uniting Biology and Chemistry in High Throughput". ACS Chem. Biol. 3 (7): 394–398. doi:10.1021/cb8001599. PMID 18642797.

External links


Category:Biotechnologists Category:Rensselaer Polytechnic Institute alumni Category:Pennsylvania State University alumni

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