Environmental Exposure; Mass Spectrometry; Metabolomics
Public Health Interests
Colorectal Cancer; Environmental Health
School of Public Health: Caroline Johnson Lab
WHRY Pilot Project Program Investigators
Extensive Research Description
Microbial metabolites and colon cancer
Colon cancers that present on the right versus the left side of the colon have significantly worse prognosis for the patient. A recent discovery revealed that right-sided colon cancers (RCCs) harbor mucosal bacterial biofilms, whereas left-sided colon cancers (LCC) are predominantly devoid of biofilms. These biofilms are associated with increased cellular proliferation and inflammation even in normal colon tissues. Using mass spectrometry-based metabolomics, we investigated the metabolism of colon cancers with and without biofilms, and observed a correlation between increased diacetylspermine production and biofilm presence on RCCs. Using antibiotic treatment, IHC, and stable isotope-assisted metabolomics we showed that diacetylspermine is an end product of polyamine metabolism produced by bacterial biofilms. We thus hypothesized that microbiota use host-derived polyamines to form biofilms. It is still not known why biofilms only form only on RCC, but it could be due to other factors such as diet and genetic predisposition.
Therefore, we aim are to examine the influence of these factors in LCC and RCC pathogenicity by investigating the roles of dietary metabolites, microbial communities and genetic predisposition.
Human exposure to chemicals in artificial turf
Artificial turf fields contain crumb rubber infill recycled from tires. Studies have shown that rubber crumb taken from synthetic turf fields contain hazardous materials such as volatile organic chemicals, including polycyclic aromatic hydrocarbons, and semi volatile organic chemicals. Over the past several years, worldwide public health concerns have been raised about the potential exposure of athletes to these compounds through inhalation, ingestion, or dermal contact with tire crumb rubber. However, exposure and health data are very limited. Using mass spectrometry approaches and questionnaire data I will be assessing human exposure and short-term health effects of activities on artificial turf fields.
Assessment of chemical exposures and adverse pregnancy outcomes
Preterm birth can cause serious life-long health problems for the child, importantly it is the greatest contributor to neonatal mortality. One of the major causes for preterm birth is preterm premature rupture of the membranes (PPROM). The mechanism for PPROM is unknown but hypothesized to be caused by placental inflammation which induces early labor. One potential mediator of placental inflammation is exposure to environmental toxins.In the Johnson Lab we will be developing methods for measuring exposures during pregnancy and identify novel mechanisms for PPROM. We will be using samples collected locally from the Yale Pregnancy and prediction Outcome Study (YPOPS) http://ypops.yale.edu/
Metabolomics guided pathway analysis reveals link between cancer metastasis, cholesterol sulfate, and phospholipids.
Johnson CH, Santidrian AF, LeBoeuf SE, Kurczy ME, Rattray NJW, Rattray Z, Warth B, Ritland M, Hoang LT, Loriot C, Higa J, Hansen JE, Felding BH, Siuzdak G. Cancer Metab. 2017 Oct 31;5:9. doi: 10.1186/s40170-017-0171-2. eCollection 2017.
Exposome-Scale Investigations Guided by Global Metabolomics, Pathway Analysis, and Cognitive Computing
Warth B, Spangler S, Fang M, Johnson CH, Forsberg EM, Granados A, Martin RL, Domingo-Almenara X, Huan T, Rinehart D, Montenegro-Burke JR, Hilmers B, Aisporna AE, Hoang LT, Uritboonthai W, Benton HP, Richardson SD, Williams AJ, Siuzdak G. Anal Chem. 2017 Sept
Systems biology guided by XCMS Online metabolomics
Huan T, Forsberg EM, Rinehart D, Johnson CH, Ivanisevic J, Benton HP, Fang M, Aisporna A, Hilmers B, Poole FL, Thorgersen MP, Adams MWW, Krantz G, Fields MW, Robbins PD, Niedernhofer LJ, Ideker T, Majumder EL, Wall JD, Rattray NJW, Goodacre R, Lairson LL, Siuzdak G. Nat Methods. 2017 14: 461–462.
Environmental Influences in the Etiology of Colorectal Cancer: the Premise of Metabolomics
Rattray NJW, Charkoftaki G, Rattray Z, Hansen JE, Vasiliou, V, Johnson CH. Curr Pharmacol Rep (2017). doi:10.1007/s40495-017-0088-z
Metabolomics: beyond biomarkers and towards mechanisms.
Johnson CH, Ivanisevic J, Siuzdak G. Nat Rev Mol Cell Biol. 2016 Jul;17(7):451-9
Global metabolomics reveals metabolic dysregulation in ischemic retinopathy.
Paris LP, Johnson CH, Aguilar E, Usui Y, Cho K, Hoang LT, Feitelberg D, Benton HP, Westenskow PD, Kurihara T, Trombley J, Tsubota K, Ueda S, Wakabayashi Y, Patti GJ, Ivanisevic J, Siuzdak G, Friedlander M. Metabolomics. 2016;12(1):15
Metabolism links bacterial biofilms and colon carcinogenesis.
Johnson CH, Dejea CM, Edler D, Hoang LT, Santidrian AF, Felding BH, Ivanisevic J, Cho K, Wick EC, Hechenbleikner EM, Uritboonthai W, Goetz L, Casero RA Jr, Pardoll DM, White JR, Patti GJ, Sears CL, Siuzdak G. Cell Metab. 2015 Jun 2;21(6):891-7.
Bioinformatics: the next frontier of metabolomics.
Johnson CH, Ivanisevic J, Benton HP, Siuzdak G. Anal Chem. 2015 Jan 6;87(1):147-56.
Metabolomic data streaming for biology-dependent data acquisition.
Rinehart D, Johnson CH, Nguyen T, Ivanisevic J, Benton HP, Lloyd J, Arkin AP, Deutschbauer AM, Patti GJ, Siuzdak G. Nat Biotechnol. 2014 Jun;32(6):524-7.
Luciferase does not Alter Metabolism in Cancer Cells.
Johnson CH, Fisher TS, Hoang LT, Felding BH, Siuzdak G, O'Brien PJ. Metabolomics. 2014 Jun 1;10(3):354-360.
Liquid chromatography quadrupole time-of-flight mass spectrometry characterization of metabolites guided by the METLIN database.
Zhu ZJ, Schultz AW, Wang J, Johnson CH, Yannone SM, Patti GJ, Siuzdak G. Nat Protoc. 2013 Mar;8(3):451-60.
Cytochrome P450 regulation by α-tocopherol in Pxr-null and PXR-humanized mice.
Johnson CH, Bonzo JA, Cheng J, Krausz KW, Kang DW, Luecke H, Idle JR, Gonzalez FJ. Drug Metab Dispos. 2013 Feb;41(2):406-13
Novel metabolites and roles for α-tocopherol in humans and mice discovered by mass spectrometry-based metabolomics.
Johnson CH, Slanař O, Krausz KW, Kang DW, Patterson AD, Kim JH, Luecke H, Gonzalez FJ, Idle JR. Am J Clin Nutr. 2012 Oct;96(4):818-30.
Radiation metabolomics. 5. Identification of urinary biomarkers of ionizing radiation exposure in nonhuman primates by mass spectrometry-based metabolomics.
Johnson CH, Patterson AD, Krausz KW, Kalinich JF, Tyburski JB, Kang DW, Luecke H, Gonzalez FJ, Blakely WF, Idle JR. Radiat Res. 2012 Oct;178(4):328-40.