Pawel K. Lorkiewicz, Ph.D.

Associate Professor of Chemistry
Division of Environmental Medicine
Department of Medicine

Education and Training

• Ph.D.: University of Louisville, Analytical Chemistry
• Postdoctoral Fellowship: University of Louisville, Stable Isotope Resolved Metabolomics

Research

Keywords

Mass Spectrometry, LC-MS, Exposomics, Stable Isotope Resolved Metabolomics, Biomarkers of Exposure, Xenobiotics, VOCs, Tobacco Regulatory Research, Metabolites, Metabolite Profiling, Core Laboratory

Research Goals

To establish a state-of-the-art shared equipment mass spectrometry facility and develop comprehensive methodologies for the analysis of small molecules and their metabolites.

Summary 

The focus of Dr. Lorkiewicz's research is to utilize mass spectrometry-based methodology in applications that help advance discovery in the fields of environmental, toxicological and basic biological research.

Dr. Lorkiewicz and his laboratory help investigators succeed by providing mass spectrometry-based services, technical expertise, education, and the development of new bioanalytical approaches.

Research Interests

Discovery, identification, and profiling of metabolites of reactive xenobiotics

• Dr. Lorkiewicz has honed his efforts on untargeted and pseudo-targeted workflows to characterize a broader portion of the exposome, particularly following the recent acquisition of a high-resolution Waters Synapt XS LC-MS system (S10 OD026840).
• His approach focuses on profiling of Phase II metabolites (mercapturates, glucuronides, sulfates, etc.) from VOCs and other reactive xenobiotics.
• Recent advancements include two UPLC-QTOF MSE DIA-based workflows for urinary mercapturome profiling and a platform for discovering biomarkers of exposure to biogenic volatile compounds (BVOCs) in urine.
• Dr. Lorkiewicz's lab has also expanded exposomics analyses to include wastewater and other matrices.

Development and implementation of workflows for Stable Isotope Resolved Metabolomics (SIRM)

• SIRM approach allows for effective pathway tracing and elucidation, tracking the fate of isotopically labeled metabolites.
• Dr. Lorkiewicz's work has focused on developing appropriate frameworks to analyze, visualize and interpret SIRM data. He recently standardized the UPLC-HRMS SIRM analysis platform for in-vivo [13C6]-glucose tracing in mice.
• He also leveraged SIRM to provide in-vivo evidence of exposures to heavy atom-labeled xenobiotics by measuring their downstream metabolites in the urine.

Instrumental analysis and measurement of biomarkers of exposure

• Dr. Lorkiewicz and his lab have supported the efforts of multiple investigators by developing applicable, targeted methods to characterize the metabolites of reactive electrophiles and xenobiotics in the urine.
• Most recently, the lab developed a high-throughput method for measuring 35 metabolites of VOCs and tobacco alkaloids in urine, utilizing the ultrahigh sensitivity of the Waters TQ Absolute system (S10OD032361).
• The lab has established robust, high-throughput LC-MS/MS methods for the detection and quantification of urinary metabolites of biogenic monoamines and their metabolites.
• Dr. Lorkiewicz's research has been instrumental in informing the design of the human tobacco study – CITU 2.0.
• Ongoing work is focused on developing additional high-throughput LC-MS/MS targeted assays (metabolites, short-chain fatty acids, vitamins, free carbonyls etc.)

Lab Members

Zhengzhi Xie, Ph.D.

Shweta Srivastava, Ph.D.

Tatiana Krivokhizhina, Ph.D.

 

Saurin Sutaria, Ph.D.

Maleesha De Silva, Ph.D.

Jin Chen, Ph.D.

David Hoetker

Featured Publications

Find all papers and citations via Google Scholar

• Xie Z, Sutaria SR, Chen JY, Gao H, Conklin DJ, Keith RJ, Srivastava S, Lorkiewicz P, Bhatnagar A. Evaluation of urinary limonene metabolites as biomarkers of exposure to greenness. Environ Res. 2024 Mar 15;245:117991. doi: 10.1016/j.envres.2023.117991. Epub 2023 Dec 22. PMID: 38141921; PMCID: PMC10922478.
• Xie Z, Chen JY, Gao H, Keith RJ, Bhatnagar A, Lorkiewicz P, Srivastava S. Global Profiling of Urinary Mercapturic Acids Using Integrated Library-Guided Analysis. Environ Sci Technol. 2023 Jul 25;57(29):10563-10573. doi: 10.1021/acs.est.2c09554. Epub 2023 Jul 11. PMID: 37432892; PMCID: PMC11064822.
• Kumar R, Adhikari S, Driver EM, Smith T, Bhatnagar A, Lorkiewicz PK, Xie Z, Hoetker JD, Halden RU. Towards a novel application of wastewater-based epidemiology in population-wide assessment of exposure to volatile organic compounds. Sci Total Environ. 2022 Nov 1;845:157008. doi: 10.1016/j.scitotenv.2022.157008. Epub 2022 Jun 27. PMID: 35772546.
• Lorkiewicz P, Keith R, Lynch J, Jin L, Theis W, Krivokhizhina T, Riggs D, Bhatnagar A, Srivastava S, Conklin DJ. Electronic Cigarette Solvents, JUUL E-Liquids, and Biomarkers of Exposure: In Vivo Evidence for Acrolein and Glycidol in E-Cig-Derived Aerosols. Chem Res Toxicol. 2022 Feb 21;35(2):283-292. doi: 10.1021/acs.chemrestox.1c00328. Epub 2022 Jan 19. PMID: 35044764; PMCID: PMC8864610.
• Fulghum KL, Audam TN, Lorkiewicz PK, Zheng Y, Merchant M, Cummins TD, Dean WL, Cassel TA, Fan TWM, Hill BG. In vivo deep network tracing reveals phosphofructokinase-mediated coordination of biosynthetic pathway activity in the myocardium. J Mol Cell Cardiol. 2022 Jan;162:32-42. doi: 10.1016/j.yjmcc.2021.08.013. Epub 2021 Sep 3. PMID: 34487754; PMCID: PMC8766935.
• McGraw KE, Riggs DW, Rai S, Navas-Acien A, Xie Z, Lorkiewicz P, Lynch J, Zafar N, Krishnasamy S, Taylor KC, Conklin DJ, DeFilippis AP, Srivastava S, Bhatnagar A. Exposure to volatile organic compounds - acrolein, 1,3-butadiene, and crotonaldehyde - is associated with vascular dysfunction. Environ Res. 2021 May;196:110903. doi: 10.1016/j.envres.2021.110903. Epub 2021 Feb 24. PMID: 33636185; PMCID: PMC8119348.
• Tevis DS, Flores SR, Kenwood BM, Bhandari D, Jacob P 3rd, Liu J, Lorkiewicz PK, Conklin DJ, Hecht SS, Goniewicz ML, Blount BC, De Jesús VR. Harmonization of acronyms for volatile organic compound metabolites using a standardized naming system. Int J Hyg Environ Health. 2021 Jun;235:113749. doi: 10.1016/j.ijheh.2021.113749. Epub 2021 May 4. Erratum in: Int J Hyg Environ Health. 2023 Jan;247:114030. doi: 10.1016/j.ijheh.2022.114030. PMID: 33962120; PMCID: PMC9019778.
• Jin L, Lorkiewicz P, Xie Z, Bhatnagar A, Srivastava S, Conklin DJ. Acrolein but not its metabolite, 3-Hydroxypropylmercapturic acid (3HPMA), activates vascular transient receptor potential Ankyrin-1 (TRPA1): Physiological to toxicological implications. Toxicol Appl Pharmacol. 2021 Sep 1;426:115647. doi: 10.1016/j.taap.2021.115647. Epub 2021 Jul 13. PMID: 34271065; PMCID: PMC8343963.
• Yeager R, Riggs DW, DeJarnett N, Srivastava S, Lorkiewicz P, Xie Z, Krivokhizhina T, Keith RJ, Srivastava S, Browning MHEM, Zafar N, Krishnasamy S, DeFilippis A, Turner J, Rai SN, Bhatnagar A. Association between residential greenness and exposure to volatile organic compounds. Sci Total Environ. 2020 Mar 10;707:135435. doi: 10.1016/j.scitotenv.2019.135435. Epub 2019 Nov 23. PMID: 31865083; PMCID: PMC7294698.
• Keith RJ, Fetterman JL, Orimoloye OA, Dardari Z, Lorkiewicz PK, Hamburg NM, DeFilippis AP, Blaha MJ, Bhatnagar A. Characterization of Volatile Organic Compound Metabolites in Cigarette Smokers, Electronic Nicotine Device Users, Dual Users, and Nonusers of Tobacco. Nicotine Tob Res. 2020 Feb 6;22(2):264-272. doi: 10.1093/ntr/ntz021. PMID: 30759242; PMCID: PMC7297089.
• Lorkiewicz PK, Gibb AA, Rood BR, He L, Zheng Y, Clem BF, Zhang X, Hill BG. Integration of flux measurements and pharmacological controls to optimize stable isotope-resolved metabolomics workflows and interpretation. Sci Rep. 2019 Sep 23;9(1):13705. doi: 10.1038/s41598-019-50183-3. PMID: 31548575; PMCID: PMC6757038.
• Lombardi AA, Gibb AA, Arif E, Kolmetzky DW, Tomar D, Luongo TS, Jadiya P, Murray EK, Lorkiewicz PK, Hajnóczky G, Murphy E, Arany ZP, Kelly DP, Margulies KB, Hill BG, Elrod JW. Mitochondrial calcium exchange links metabolism with the epigenome to control cellular differentiation. Nat Commun. 2019 Oct 4;10(1):4509. doi: 10.1038/s41467-019-12103-x. PMID: 31586055; PMCID: PMC6778142.
• Xie Z, Lorkiewicz P, Riggs DW, Bhatnagar A, Srivastava S. Comprehensive, robust, and sensitive UPLC-MS/MS analysis of free biogenic monoamines and their metabolites in urine. J Chromatogr B Analyt Technol Biomed Life Sci. 2018 Nov 1;1099:83-91. doi: 10.1016/j.jchromb.2018.09.012. Epub 2018 Sep 12. PMID: 30248561; PMCID: PMC6398444.
• Lorkiewicz P, Riggs DW, Keith RJ, Conklin DJ, Xie Z, Sutaria S, Lynch B, Srivastava S, Bhatnagar A. Comparison of Urinary Biomarkers of Exposure in Humans Using Electronic Cigarettes, Combustible Cigarettes, and Smokeless Tobacco. Nicotine Tob Res. 2019 Aug 19;21(9):1228-1238. doi: 10.1093/ntr/nty089. PMID: 29868926; PMCID: PMC6698950.

Contact Information

Pawel Lorkiewicz
Christina Lee Brown Envirome Institute
pawel.lorkiewicz@louisville.edu  | 502-852-7559

Cardiovascular Innovation Institute Building, Room 211
302 E Muhammad Ali Blvd
Louisville KY 40202