Daniel  M.  Rotroff,  PhD

Daniel M. Rotroff, PhD

Assistant Staff

Lerner Research Institute, 9500 Euclid Avenue, Cleveland, Ohio 44195


We use a wide-range of computational and experimental approaches to leverage -omics technologies and electronic health records (EHR) to investigate many aspects of precision medicine, such as biomarker or risk allele discovery for drug response and disease outcomes. As a KL2 Scholar, we have funding to develop methods that utilize genomic and clinical data to identify high-risk subtypes within type 2 diabetes. Additional funded projects include the integration of genomic, behavioral, and microbiome factors into a risk model for onset of chemotherapy induced nausea and vomiting, and the use of breath-based metabolomics as a screening tool for chronic liver diseases and hepatocellular carcinoma.

Lay Summary








Genetic Variants in CPA6 and PRPF31 Are Associated With Variation in Response to Metformin in Individuals With Type 2 Diabetes.


Rotroff DM, Yee SW, Zhou K, Marvel SW, Shah HS, Jack JR, Havener TM, Hedderson MM, Kubo M, Herman MA, Gao H, Mychaleckyi JC, McLeod HL, Doria A, Giacomini KM, Pearson ER, Wagner MJ, Buse JB, Motsinger-Reif AA; MetGen Investigators; ACCORD/ACCORDion Investigators.


Diabetes. 2018 Jul;67(7):1428-1440. doi: 10.2337/db17-1164. Epub 2018 Apr 12.


PMID: 29650774 [PubMed - indexed for MEDLINE] Free Article


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Targeted metabolomics and medication classification data from participants in the ADNI1 cohort.


St John-Williams L, Blach C, Toledo JB, Rotroff DM, Kim S, Klavins K, Baillie R, Han X, Mahmoudiandehkordi S, Jack J, Massaro TJ, Lucas JE, Louie G, Motsinger-Reif AA, Risacher SL; Alzheimer’s Disease Neuroimaging Initiative; Alzheimer’s Disease Metabolomics Consortium, Saykin AJ, Kastenmüller G, Arnold M, Koal T, Moseley MA, Mangravite LM, Peters MA, Tenenbaum JD, Thompson JW, Kaddurah-Daouk R.


Sci Data. 2017 Oct 17;4:170140. doi: 10.1038/sdata.2017.140.


PMID: 29039849 [PubMed - indexed for MEDLINE] Free PMC Article


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Genetic Variants in HSD17B3, SMAD3, and IPO11 Impact Circulating Lipids in Response to Fenofibrate in Individuals With Type 2 Diabetes.


Rotroff DM, Pijut SS, Marvel SW, Jack JR, Havener TM, Pujol A, Schluter A, Graf GA, Ginsberg HN, Shah HS, Gao H, Morieri ML, Doria A, Mychaleckyi JC, McLeod HL, Buse JB, Wagner MJ, Motsinger-Reif AA; ACCORD/ACCORDion Investigators.


Clin Pharmacol Ther. 2018 Apr;103(4):712-721. doi: 10.1002/cpt.798. Epub 2017 Nov 3.


PMID: 28736931 [PubMed - in process] Free PMC Article


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Common and rare genetic markers of lipid variation in subjects with type 2 diabetes from the ACCORD clinical trial.


Marvel SW, Rotroff DM, Wagner MJ, Buse JB, Havener TM, McLeod HL, Motsinger-Reif AA; The ACCORD/ACCORDion Investigators.


PeerJ. 2017 May 2;5:e3187. doi: 10.7717/peerj.3187. eCollection 2017.


PMID: 28480134 [PubMed] Free PMC Article


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Metabolic network failures in Alzheimer's disease: A biochemical road map.


Toledo JB, Arnold M, Kastenmüller G, Chang R, Baillie RA, Han X, Thambisetty M, Tenenbaum JD, Suhre K, Thompson JW, John-Williams LS, MahmoudianDehkordi S, Rotroff DM, Jack JR, Motsinger-Reif A, Risacher SL, Blach C, Lucas JE, Massaro T, Louie G, Zhu H, Dallmann G, Klavins K, Koal T, Kim S, Nho K, Shen L, Casanova R, Varma S, Legido-Quigley C, Moseley MA, Zhu K, Henrion MYR, van der Lee SJ, Harms AC, Demirkan A, Hankemeier T, van Duijn CM, Trojanowski JQ, Shaw LM, Saykin AJ, Weiner MW, Doraiswamy PM, Kaddurah-Daouk R; Alzheimer's Disease Neuroimaging Initiative and the Alzheimer Disease Metabolomics Consortium.


Alzheimers Dement. 2017 Sep;13(9):965-984. doi: 10.1016/j.jalz.2017.01.020. Epub 2017 Mar 22.


PMID: 28341160 [PubMed - indexed for MEDLINE] Free PMC Article


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Maternal smoking impacts key biological pathways in newborns through epigenetic modification in Utero.


Rotroff DM, Joubert BR, Marvel SW, Håberg SE, Wu MC, Nilsen RM, Ueland PM, Nystad W, London SJ, Motsinger-Reif A.


BMC Genomics. 2016 Nov 25;17(1):976.


PMID: 27887572 [PubMed - indexed for MEDLINE] Free PMC Article


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Incorporating Concomitant Medications into Genome-Wide Analyses for the Study of Complex Disease and Drug Response.


Graham HT, Rotroff DM, Marvel SW, Buse JB, Havener TM, Wilson AG, Wagner MJ, Motsinger-Reif AA; ACCORD/ACCORDion Investigators.


Front Genet. 2016 Aug 17;7:138. eCollection 2016.


PMID: 27775101 [PubMed] Free PMC Article


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Metabolomic signatures of drug response phenotypes for ketamine and esketamine in subjects with refractory major depressive disorder: new mechanistic insights for rapid acting antidepressants.


Rotroff DM, Corum DG, Motsinger-Reif A, Fiehn O, Bottrel N, Drevets WC, Singh J, Salvadore G, Kaddurah-Daouk R.


Transl Psychiatry. 2016 Sep 20;6(9):e894. doi: 10.1038/tp.2016.145.


PMID: 27648916 [PubMed - indexed for MEDLINE] Free PMC Article


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Comprehensive genomic characterization of five canine lymphoid tumor cell lines.


Roode SC, Rotroff D, Richards KL, Moore P, Motsinger-Reif A, Okamura Y, Mizuno T, Tsujimoto H, Suter SE, Breen M.


BMC Vet Res. 2016 Sep 17;12:207. doi: 10.1186/s12917-016-0836-z.


PMID: 27639374 [PubMed - indexed for MEDLINE] Free PMC Article


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Variation in the glucose transporter gene SLC2A2 is associated with glycemic response to metformin.


Zhou K, Yee SW, Seiser EL, van Leeuwen N, Tavendale R, Bennett AJ, Groves CJ, Coleman RL, van der Heijden AA, Beulens JW, de Keyser CE, Zaharenko L, Rotroff DM, Out M, Jablonski KA, Chen L, Javorský M, Židzik J, Levin AM, Williams LK, Dujic T, Semiz S, Kubo M, Chien HC, Maeda S, Witte JS, Wu L, Tkáč I, Kooy A, van Schaik RHN, Stehouwer CDA, Logie L; MetGen Investigators; DPP Investigators; ACCORD Investigators, Sutherland C, Klovins J, Pirags V, Hofman A, Stricker BH, Motsinger-Reif AA, Wagner MJ, Innocenti F, 't Hart LM, Holman RR, McCarthy MI, Hedderson MM, Palmer CNA, Florez JC, Giacomini KM, Pearson ER.


Nat Genet. 2016 Sep;48(9):1055-1059. doi: 10.1038/ng.3632. Epub 2016 Aug 8.


PMID: 27500523 [PubMed - indexed for MEDLINE] Free PMC Article


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Pharmacometabolomic Assessment of Metformin in Non-diabetic, African Americans.


Rotroff DM, Oki NO, Liang X, Yee SW, Stocker SL, Corum DG, Meisner M, Fiehn O, Motsinger-Reif AA, Giacomini KM, Kaddurah-Daouk R.


Front Pharmacol. 2016 Jun 14;7:135. doi: 10.3389/fphar.2016.00135. eCollection 2016.


PMID: 27378919 [PubMed] Free PMC Article


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A genome-wide study of lipid response to fenofibrate in Caucasians: a combined analysis of the GOLDN and ACCORD studies.


Irvin MR, Rotroff DM, Aslibekyan S, Zhi D, Hidalgo B, Motsinger-Reif A, Marvel S, Srinivasasainagendra V, Claas SA, Buse JB, Straka RJ, Ordovas JM, Borecki IB, Guo X, Chen IY, Rotter JI, Wagner MJ, Arnett DK.


Pharmacogenet Genomics. 2016 Jul;26(7):324-33. doi: 10.1097/FPC.0000000000000219.


PMID: 27002377 [PubMed - indexed for MEDLINE] Free PMC Article


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Pharmacometabolomic Assessments of Atenolol and Hydrochlorothiazide Treatment Reveal Novel Drug Response Phenotypes.


Rotroff DM, Shahin MH, Gurley SB, Zhu H, Motsinger-Reif A, Meisner M, Beitelshees AL, Fiehn O, Johnson JA, Elbadawi-Sidhu M, Frye RF, Gong Y, Weng L, Cooper-DeHoff RM, Kaddurah-Daouk R.


CPT Pharmacometrics Syst Pharmacol. 2015 Nov;4(11):669-79. doi: 10.1002/psp4.12017. Epub 2015 Oct 29.


PMID: 26783503 [PubMed] Free PMC Article


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Genome-wide assessment of recurrent genomic imbalances in canine leukemia identifies evolutionarily conserved regions for subtype differentiation.


Roode SC, Rotroff D, Avery AC, Suter SE, Bienzle D, Schiffman JD, Motsinger-Reif A, Breen M.


Chromosome Res. 2015 Dec;23(4):681-708. doi: 10.1007/s10577-015-9475-7. Epub 2015 Jun 3.


PMID: 26037708 [PubMed - indexed for MEDLINE]


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Predictive endocrine testing in the 21st century using in vitro assays of estrogen receptor signaling responses.


Rotroff DM, Martin MT, Dix DJ, Filer DL, Houck KA, Knudsen TB, Sipes NS, Reif DM, Xia M, Huang R, Judson RS.


Environ Sci Technol. 2014;48(15):8706-16. doi: 10.1021/es502676e. Epub 2014 Jul 10.


PMID: 24960280 [PubMed - indexed for MEDLINE]


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Lymphoblastoid cell lines models of drug response: successes and lessons from this pharmacogenomic model.


Jack J, Rotroff D, Motsinger-Reif A.


Curr Mol Med. 2014;14(7):833-40.


PMID: 25109794 [PubMed - indexed for MEDLINE] Free PMC Article


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Naturally occuring canine cancers: powerful models for stimulating pharmacogenomic advancement in human medicine.


Rotroff DM, Thomas R, Breen M, Motsinger-Reif AA.


Pharmacogenomics. 2013 Dec;14(16):1929-31. doi: 10.2217/pgs.13.178. No abstract available.


PMID: 24279843 [PubMed - indexed for MEDLINE] Free Article


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Real-time growth kinetics measuring hormone mimicry for ToxCast chemicals in T-47D human ductal carcinoma cells.


Rotroff DM, Dix DJ, Houck KA, Kavlock RJ, Knudsen TB, Martin MT, Reif DM, Richard AM, Sipes NS, Abassi YA, Jin C, Stampfl M, Judson RS.


Chem Res Toxicol. 2013 Jul 15;26(7):1097-107. doi: 10.1021/tx400117y. Epub 2013 Jun 10.


PMID: 23682706 [PubMed - indexed for MEDLINE]


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Using in vitro high throughput screening assays to identify potential endocrine-disrupting chemicals.


Rotroff DM, Dix DJ, Houck KA, Knudsen TB, Martin MT, McLaurin KW, Reif DM, Crofton KM, Singh AV, Xia M, Huang R, Judson RS.


Environ Health Perspect. 2013 Jan;121(1):7-14. doi: 10.1289/ehp.1205065. Epub 2012 Sep 28.


PMID: 23052129 [PubMed - indexed for MEDLINE] Free PMC Article


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Update on EPA's ToxCast program: providing high throughput decision support tools for chemical risk management.


Kavlock R, Chandler K, Houck K, Hunter S, Judson R, Kleinstreuer N, Knudsen T, Martin M, Padilla S, Reif D, Richard A, Rotroff D, Sipes N, Dix D.


Chem Res Toxicol. 2012 Jul 16;25(7):1287-302. doi: 10.1021/tx3000939. Epub 2012 May 15.


PMID: 22519603 [PubMed - indexed for MEDLINE]


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Incorporating human dosimetry and exposure into high-throughput in vitro toxicity screening.


Rotroff DM, Wetmore BA, Dix DJ, Ferguson SS, Clewell HJ, Houck KA, Lecluyse EL, Andersen ME, Judson RS, Smith CM, Sochaski MA, Kavlock RJ, Boellmann F, Martin MT, Reif DM, Wambaugh JF, Thomas RS.


Toxicol Sci. 2010 Oct;117(2):348-58. doi: 10.1093/toxsci/kfq220. Epub 2010 Jul 16. Erratum in: Toxicol Sci. 2014 Feb;137(2):499. Dosage error in article text.


PMID: 20639261 [PubMed - indexed for MEDLINE] Free PMC Article


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Analysis of eight oil spill dispersants using rapid, in vitro tests for endocrine and other biological activity.


Judson RS, Martin MT, Reif DM, Houck KA, Knudsen TB, Rotroff DM, Xia M, Sakamuru S, Huang R, Shinn P, Austin CP, Kavlock RJ, Dix DJ.


Environ Sci Technol. 2010 Aug 1;44(15):5979-85. doi: 10.1021/es102150z.


PMID: 20602530 [PubMed - indexed for MEDLINE] Free PMC Article


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Xenobiotic-metabolizing enzyme and transporter gene expression in primary cultures of human hepatocytes modulated by ToxCast chemicals.


Rotroff DM, Beam AL, Dix DJ, Farmer A, Freeman KM, Houck KA, Judson RS, LeCluyse EL, Martin MT, Reif DM, Ferguson SS.


J Toxicol Environ Health B Crit Rev. 2010 Feb;13(2-4):329-46. doi: 10.1080/10937404.2010.483949.


PMID: 20574906 [PubMed - indexed for MEDLINE]


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In vitro screening of environmental chemicals for targeted testing prioritization: the ToxCast project.


Judson RS, Houck KA, Kavlock RJ, Knudsen TB, Martin MT, Mortensen HM, Reif DM, Rotroff DM, Shah I, Richard AM, Dix DJ.


Environ Health Perspect. 2010 Apr;118(4):485-92. doi: 10.1289/ehp.0901392.


PMID: 20368123 [PubMed - indexed for MEDLINE] Free PMC Article


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04/26/2021 |  

New Analysis of Previous Trial Results Offers Insights into Personalized Care for Type 2 Diabetes

Dr. Rotroff and team found that genetic variation may help to identify diabetes patients at risk for cardiovascular disease who may benefit from aggressive glycemia treatment.

11/16/2020 |  

Researchers Embark on New Study to Identify Predictors of Chemotherapy-Associated Pain Condition

Dr. Rotroff and clinical collaborator Dr. Foss will compare genetic, epigenetic and metabolomic data from breast cancer patients who experience the condition versus those who don’t in an effort to develop a predictive machine learning-based algorithm for personalized risk.