研究领域
We live in a 3D world!
We use our chemical cartography approach to understand the spatial context of disease development, by investigating the chemical interplay between mammalian hosts, their environment and microorganisms in 3D. Using mass spectrometry-based metabolomics, combined with big data statistical tools and three-dimensional modeling, we place molecules in their spatial context and link them to microbial community composition and human health. This approach helps us determine how a given micro-environment influences pathogen tropism, how antimicrobial sensitivity is spatially variable, and how we interact with our environment, with many other exciting possible applications! We then use this information to guide rational drug and vaccine development and changes in health practices, so that our discoveries can be translated into applications that improve human health, with a particular focus on neglected tropical diseases and diseases of poverty.
Current work focuses on:
1. Applying chemical cartography to define the chemical rules of pathogen and disease tropism. Why do diseases happen where they do in the world? Why do pathogens colonize one organ but not another? Why do some organ locations recover from infection and others stay permanently damaged? We use our unique method to address these questions across a range of viral and parasitic disease systems. This work has important implications for how we diagnose and treat disease.
2. Applying chemical cartography and metabolomics to understand microbiome function. Although the role of the microbiome in health and disease is now well established, the mechanisms by which the microbiome influences health are still not fully understood. Our 3D perspective helps us understand the changes happening locally at the site of microbial colonization and on a global scale, and then to connect these changes to overall health status.
3. Spatially-resolved exposomics research. By characterizing the relationship between building surfaces, small molecules, and the human skin, we are beginning to understand how our day-to-day lives put us in constant contact with a variety of chemicals, some of which have the potential to affect our health. This research topic is being developed in the context of investigation-driven graduate courses and hands-on undergraduate research.
4. Translational implementations of chemical cartography. Characterizing chemical interactions between humans, their environment, and microorganisms is only the first step! We use our data to develop new sensitive diagnostic tests to assess disease severity and infection outcome. We also explore whether modulating local signals affect pathogen tropism and disease progression, in a drug development framework. Our spatial perspective enables us to redefine the factors controlling phenotypic resistance to antimicrobials, test how drug sensitivity varies within a given organ or tissue, and develop new approaches to clear dormant organisms. Finally, we are also interested in using our data to develop and improve rational immunization strategies for parasitic diseases. We focus on diseases where the clinical need is most acute, including Chagas disease and leishmaniasis. This is achieved in-house through our pre-clinical animal model systems, and via clinical collaborations.
近期论文
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Dysregulation of Glycerophosphocholines in the Cutaneous Lesion Caused by Leishmania major in Experimental Murine Models. Parab AR, Thomas D, Lostracco-Johnson S, Siqueira-Neto JL, McKerrow JH, Dorrestein PC, McCall LI. Pathogens. 2021 May 13;10(5):593. doi: 10.3390/pathogens10050593. PMID: 34068119
Alterations to the Cardiac Metabolome Induced by Chronic T. cruzi Infection Relate to the Degree of Cardiac Pathology. Hoffman K, Liu Z, Hossain E, Bottazzi ME, Hotez PJ, Jones KM, McCall LI. ACS Infect Dis. 2021 Apr 12. doi: 10.1021/acsinfecdis.0c00816. Online ahead of print. PMID: 33843195
Quo vadis? Central Rules of Pathogen and Disease Tropism. McCall LI. Front Cell Infect Microbiol. 2021 Feb 25;11:640987. doi: 10.3389/fcimb.2021.640987. eCollection 2021. PMID: 33718287
Tryp-ing Up Metabolism: Role of Metabolic Adaptations in Kinetoplastid Disease Pathogenesis. Parab AR, McCall LI. Infect Immun. 2021 Mar 17;89(4):e00644-20. doi: 10.1128/IAI.00644-20. Print 2021 Mar 17. PMID: 33526564
ReDU: a framework to find and reanalyze public mass spectrometry data. Jarmusch AK, Wang M, Aceves CM, Advani RS, Aguirre S, Aksenov AA, Aleti G, Aron AT, Bauermeister A, Bolleddu S, Bouslimani A, Caraballo Rodriguez AM, Chaar R, Coras R, Elijah EO, Ernst M, Gauglitz JM, Gentry EC, Husband M, Jarmusch SA, Jones KL 2nd, Kamenik Z, Le Gouellec A, Lu A, McCall LI, McPhail KL, Meehan MJ, Melnik AV, Menezes RC, Montoya Giraldo YA, Nguyen NH, Nothias LF, Nothias-Esposito M, Panitchpakdi M, Petras D, Quinn RA, Sikora N, van der Hooft JJJ, Vargas F, Vrbanac A, Weldon KC, Knight R, Bandeira N, Dorrestein PC. Nat Methods. 2020 Sep;17(9):901-904. doi: 10.1038/s41592-020-0916-7. Epub 2020 Aug 17. PMID: 32807955
Mapping of host-parasite-microbiome interactions reveals metabolic determinants of tropism and tolerance in Chagas disease. Hossain E, Khanam S, Dean DA, Wu C, Lostracco-Johnson S, Thomas D, Kane SS, Parab AR, Flores K, Katemauswa M, Gosmanov C, Hayes SE, Zhang Y, Li D, Woelfel-Monsivais C, Sankaranarayanan K, McCall LI. Sci Adv. 2020 Jul 22;6(30):eaaz2015. doi: 10.1126/sciadv.aaz2015. eCollection 2020 Jul. PMID: 32766448
Insights gained into respiratory infection pathogenesis using lung tissue metabolomics. Bernatchez JA, McCall LI. PLoS Pathog. 2020 Jul 14;16(7):e1008662. doi: 10.1371/journal.ppat.1008662. eCollection 2020 Jul. PMID: 32663224
Scaffold and Parasite Hopping: Discovery of New Protozoal Proliferation Inhibitors. Singh B, Bernatchez JA, McCall LI, Calvet CM, Ackermann J, Souza JM, Thomas D, Silva EM, Bachovchin KA, Klug DM, Jalani HB, Bag S, Buskes MJ, Leed SE, Roncal NE, Penn EC, Erath J, Rodriguez A, Sciotti RJ, Campbell RF, McKerrow J, Siqueira-Neto JL, Ferrins L, Pollastri MP. ACS Med Chem Lett. 2020 Jan 10;11(3):249-257. doi: 10.1021/acsmedchemlett.9b00453. eCollection 2020 Mar 12. PMID: 32184953
Local Phenomena Shape Backyard Soil Metabolite Composition. Nguyen TD, Lesani M, Forrest I, Lan Y, Dean DA, Gibaut QMR, Guo Y, Hossain E, Olvera M, Panlilio H, Parab AR, Wu C, Bernatchez JA, Cichewicz RH, McCall LI. Metabolites. 2020 Feb 29;10(3):86. doi: 10.3390/metabo10030086. PMID: 32121389
Home chemical and microbial transitions across urbanization. McCall LI, Callewaert C, Zhu Q, Song SJ, Bouslimani A, Minich JJ, Ernst M, Ruiz-Calderon JF, Cavallin H, Pereira HS, Novoselac A, Hernandez J, Rios R, Branch OH, Blaser MJ, Paulino LC, Dorrestein PC, Knight R, Dominguez-Bello MG. Nat Microbiol. 2019 Nov 4. doi: 10.1038/s41564-019-0593-4. PMID: 31686026
Ethical priority of the most actionable system of biomolecules: the metabolome. Lewis CM Jr, McCall LI, Sharp RR, Spicer PG. Am J Phys Anthropol. 2019 Oct 23. doi: 10.1002/ajpa.23943. PMID: 31643083
Design of Gallinamide A Analogs as Potent Inhibitors of the Cysteine Proteases Human Cathepsin L and Trypanosoma cruzi Cruzain. Boudreau PD, Miller BW, McCall LI, Almaliti J, Reher R, Hirata K, Le T, Siqueira-Neto JL, Hook V, Gerwick WH. J Med Chem. 2019 Oct 24;62(20):9026-9044. doi: 10.1021/acs.jmedchem.9b00294. PMID: 31539239
A complete Leishmania donovani reference genome identifies novel genetic variations associated with virulence. Lypaczewski P, Hoshizaki J, Zhang WW, McCall LI, Torcivia-Rodriguez J, Simonyan V, Kaur A, Dewar K, Matlashewski G. Sci Rep. 2018 Nov 8;8(1):16549. doi: 10.1038/s41598-018-34812-x. PMID: 30409989
Cysteine proteases in protozoan parasites. Siqueira-Neto JL, Debnath A, McCall LI, Bernatchez JA, Ndao M, Reed SL, Rosenthal PJ. PLoS Negl Trop Dis. 2018 Aug 23;12(8):e0006512. doi: 10.1371/journal.pntd.0006512. PMID: 30138453
Best practices for analysing microbiomes. Knight R, Vrbanac A, Taylor BC, Aksenov A, Callewaert C, Debelius J, Gonzalez A, Kosciolek T, McCall LI, McDonald D, Melnik AV, Morton JT, Navas J, Quinn RA, Sanders JG, Swafford AD, Thompson LR, Tripathi A, Xu ZZ, Zaneveld JR, Zhu Q, Caporaso JG, Dorrestein PC. Nat Rev Microbiol. 2018 Jul;16(7):410-422. doi: 10.1038/s41579-018-0029-9. PMID: 29795328
Metabolomics: Eavesdropping on silent conversations between hosts and their unwelcome guests. Newsom SN, McCall LI. PLoS Pathog. 2018 Apr 5;14(4):e1006926. doi: 10.1371/journal.ppat.1006926. PMID: 29621358
Experimental Chagas disease-induced perturbations of the fecal microbiome and metabolome. McCall LI, Tripathi A, Vargas F, Knight R, Dorrestein PC, Siqueira-Neto JL. PLoS Negl Trop Dis. 2018 Mar 12;12(3):e0006344. doi: 10.1371/journal.pntd.0006344. PMID: 29529084
Mass Spectrometry-Based Chemical Cartography of a Cardiac Parasitic Infection. McCall LI, Morton JT, Bernatchez JA, de Siqueira-Neto JL, Knight R, Dorrestein PC, McKerrow JH. Anal Chem. 2017 Oct 3;89(19):10414-10421. doi: 10.1021/acs.analchem.7b02423. Epub 2017 Sep 22. PMID: 28892370
Rapid Chagas Disease Drug Target Discovery Using Directed Evolution in Drug-Sensitive Yeast. Ottilie S, Goldgof GM, Calvet CM, Jennings GK, LaMonte G, Schenken J, Vigil E, Kumar P, McCall LI, Lopes ES, Gunawan F, Yang J, Suzuki Y, Siqueira-Neto JL, McKerrow JH, Amaro RE, Podust LM, Durrant JD, Winzeler EA. ACS Chem Biol. 2017 Feb 17;12(2):422-434. doi: 10.1021/acschembio.6b01037. Epub 2016 Dec 23. PMID: 27977118
Mass Spectrometry-Based Visualization of Molecules Associated with Human Habitats. Petras D, Nothias LF, Quinn RA, Alexandrov T, Bandeira N, Bouslimani A, Castro-Falcón G, Chen L, Dang T, Floros DJ, Hook V, Garg N, Hoffner N, Jiang Y, Kapono CA, Koester I, Knight R, Leber CA, Ling TJ, Luzzatto-Knaan T, McCall LI, McGrath AP, Meehan MJ, Merritt JK, Mills RH, Morton J, Podvin S, Protsyuk I, Purdy T, Satterfield K, Searles S, Shah S, Shires S, Steffen D, White M, Todoric J, Tuttle R, Wojnicz A, Sapp V, Vargas F, Yang J, Zhang C, Dorrestein PC. Anal Chem. 2016 Nov 15;88(22):10775-10784. Epub 2016 Oct 24. PMID: 27732780
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