Rheem Totah

Education

• B.S. (Honors), 1995, Birzeit University, Palestine
• Masters (Honors), 2000, University of Kansas
• Ph.D. (Honors), 2002, University of Kansas

Research Interests

• Prescription drug negative side effects in the heart, skeletal muscle and bone; associated chemical mechanisms for this toxicity
• Drug-endogenous substrate interactions
• Pharmacogenetics

Taking Students: Yes

Biography

Dr. Totah obtained her bachelor’s degree in chemistry from Birzeit University in Palestine and her master’s and PhD in medicinal chemistry from the University of Kansas. Dr. Totah is currently a professor in the Department of Medicinal Chemistry. Her research is in the area of prescription drug negative side effects especially in the heart, skeletal muscle and bone. She focuses on researching the chemical mechanisms for this toxicity. Her research is important in guiding research towards medicines with fewer side effects and safer use. Research in the Totah lab is broadly centered on drug-endogenous substrate interactions.

Recent Publications

The methyltransferases METTL7A and METTL7B confer resistance to thiol-based histone deacetylase inhibitors. Robey RW, Fitzsimmons CM, Guiblet WM, Frye WJE, González Dalmasy JM, Wang L, Russell DA, Huff LM, Perciaccante AJ, Ali-Rahmani F, Lipsey CC, Wade HM, Mitchell AV, Maligireddy SS, Terrero D, Butcher D, Edmondson EF, Jenkins LM, Nikitina T, Zhurkin VB, Tiwari AK, Piscopio AD, Totah RA, Bates SE, Arda HE, Gottesman MM, Batista PJ.Mol Cancer Ther. 2023 Dec 28. doi: 10.1158/1535-7163.MCT-23-0144. Online ahead of print. PMID: 38151817

Cardioprotective mechanisms of cytochrome P450 derived oxylipins from ω-3 and ω-6 PUFAs. Cho C, Aliwarga T, Wiley AM, Totah RA. Adv Pharmacol. 2023;97:201-227. doi: 10.1016/bs.apha.2023.02.001. Epub 2023 Mar 27.

METTL7A (TMT1A) and METTL7B (TMT1B) are responsible for alkyl S-thiol methyl transferase activity in liver. Russell DA, Chau MK, Shi Y, Levasseur IN, Maldonato BJ, Totah RA.Drug Metab Dispos. 2023 May 3:DMD-AR-2023-001268. doi: 10.1124/dmd.123.001268. Online ahead of print.

Plasma hydrogen sulfide, nitric oxide, and thiocyanate levels are lower during pregnancy compared to postpartum in a cohort of women from the Pacific northwest of the United States. Zeigler MB, Fay EE, Moreni SL, Mao J, Totah RA, Hebert MF.Life Sci. 2023 Jun 1;322:121625. doi: 10.1016/j.lfs.2023.121625. Epub 2023 Mar 30.

The Effects of Pregnancy on Amino Acid Levels and Nitrogen Disposition. Enthoven LF, Shi Y, Fay EE, Moreni S, Mao J, Honeyman EM, Smith CK, Whittington D, Brockerhoff SE, Isoherranen N, Totah RA, Hebert MF.Metabolites. 2023 Feb 7;13(2):242. doi: 10.3390/metabo13020242.

Cardiac Disease Alters Myocardial Tissue Levels of Epoxyeicosatrienoic Acids and Key Proteins Involved in Their Biosynthesis and Degradation.Aliwarga T, Dinh JC, Heyward S, Prasad B, Gharib SA, Lemaitre RN, Sotoodehnia N, Totah RA.Int J Mol Sci. 2022 Oct 17;23(20):12433. doi: 10.3390/ijms232012433. PMID: 36293289

Selective deuteration of bupropion slows epimerization and reduces metabolism.Shi Y, Dinh J, Pelletier R, Raccor B, Yusuff N, Morgan AJ, Harbeson S, Uttamsingh V, Totah RA.Bioorg Med Chem Lett. 2022 Nov 15;76:129009. doi: 10.1016/j.bmcl.2022.129009. Epub 2022 Sep 27.PMID:36174836

Plasma epoxyeicosatrienoic acids and diabetes-related cardiovascular disease: The cardiovascular health study. Lemaitre RN, Jensen PN, Zeigler M, Fretts AM, Umans JG, Howard BV, Sitlani CM, McKnight B, Gharib SA, King IB, Siscovick DS, Psaty BM, Sotoodehnia N, Totah RA.EBioMedicine. 2022 Sep;83:104189. doi: 10.1016/j.ebiom.2022.104189. Epub 2022 Aug 2.

Reductions in Hydrogen Sulfide and Changes in Mitochondrial Quality Control Proteins Are Evident in the Early Phases of the Corneally Kindled Mouse Model of Epilepsy.Cho C, Zeigler M, Mizuno S, Morrison RS, Totah RA, Barker-Haliski M.Int J Mol Sci. 2022 Jan 27;23(3):1434. doi: 10.3390/ijms23031434.

Future of Biotransformation Science in the Pharmaceutical Industry. Kramlinger VM, Dalvie D, Heck CJS, Kalgutkar AS, O’Neill J, Su D, Teitelbaum AM, Totah RA.Drug Metab Dispos. 2022 Mar;50(3):258-267. doi: 10.1124/dmd.121.000658. Epub 2021 Dec 17.

Sources of Interindividual Variability. Lin YS, Thummel KE, Thompson BD, Totah RA, Cho CW.Methods Mol Biol. 2021;2342:481-550. doi: 10.1007/978-1-0716-1554-6_17.

Plasma epoxyeicosatrienoic acids and dihydroxyeicosatrieonic acids, insulin, glucose and risk of diabetes: The strong heart study. Lemaitre RN, Jensen PN, Zeigler M, Denham J, Fretts AM, Umans JG, Howard BV, Sitlani CM, McKnight B, Gharib SA, King IB, Siscovick DS, Psaty BM, Sotoodehnia N, Totah RA. EBioMedicine. 2021 Apr;66:103279. doi: 10.1016/j.ebiom.2021.103279. Epub 2021 Mar 19.

Human METTL7B is an alkyl thiol methyltransferase that metabolizes hydrogen sulfide and captopril. Maldonato BJ, Russell DA, Totah RA. Sci Rep. 2021 Mar 1;11(1):4857. doi: 10.1038/s41598-021-84218-5.

Changes in erythrocyte membrane epoxyeicosatrienoic, dihydroxyeicosatrienoic, and hydroxyeicosatetraenoic acids during pregnancy. Somani ST, Zeigler M, Fay EE, Leahy M, Bermudez B, Totah RA, Hebert MF. Life Sci. 2021 Jan 1;264:118590. doi: 10.1016/j.lfs.2020.118590. Epub 2020 Oct 15.

Characterization of Differential Tissue Abundance of Major Non-CYP Enzymes in Human. Basit A, Neradugomma NK, Wolford C, Fan PW, Murray B, Takahashi RH, Khojasteh SC, Smith BJ, Heyward S, Totah RA, Kelly EJ, Prasad B. Mol Pharm. 2020 Nov 2;17(11):4114-4124. doi: 10.1021/acs.molpharmaceut.0c00559. Epub 2020 Oct 2.

Expression and Function of Eicosanoid-Producing Cytochrome P450 Enzymes in Solid Tumors. Evangelista EA, Cho CW, Aliwarga T, Totah RA. Front Pharmacol. 2020 Jun 9;11:828. doi: 10.3389/fphar.2020.00828. eCollection 2020.

Higher Epoxyeicosatrienoic Acids in Cardiomyocytes-Specific CYP2J2 Transgenic Mice Are Associated with Improved Myocardial Remodeling. Aliwarga T, Guo X, Evangelista EA, Lemaitre RN, Sotoodehnia N, Gharib SA, Zeldin DC, Liu Q, Totah RA. Biomedicines. 2020 May 30;8(6):144. doi: 10.3390/biomedicines8060144.

CYP2J2 Modulates Diverse Transcriptional Programs in Adult Human Cardiomyocytes. Evangelista EA, Aliwarga T, Sotoodehnia N, Jensen PN, McKnight B, Lemaitre RN, Totah RA, Gharib SA. Sci Rep. 2020 Mar 24;10(1):5329. doi: 10.1038/s41598-020-62174-w.

Critical Differences between Enzyme Sources in Sensitivity to Detect Time-Dependent Inactivation of CYP2C8. Kahma H, Filppula AM, Launiainen T, Viinamäki J, Neuvonen M, Evangelista EA, Totah RA, Backman JT. Drug Metab Dispos. 2019 Apr;47(4):436-443. doi: 10.1124/dmd.118.085498. Epub 2019 Feb 1.

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