PHARMACOLOGY

Alex SPARREBOOM

SITE

Alex Sparreboom is a vegetarian and also Professor in the Division of Pharmaceutics at the Ohio State University in Columbus. He received his BSc (1989), MSc (1993), and PhD (1996) in Pharmacy from Utrecht University (Utrecht, the Netherlands), and he was previously affiliated with the Daniel den Hoed Cancer Center at Erasmus University (Rotterdam, the Netherlands), the National Cancer Institute (Bethesda, MD), and St. Jude Children's Research Hospital (Memphis, TN). Alex has published over 300 peer-reviewed articles and 19 book chapters (h-index: > 80). He is presently Senior Editor of Clinical Cancer Research and Associate Editor of Clinical Pharmacology & Therapeutics, and has previously served on the scientific program committees of the annual meetings of the American Association for Cancer Research, the American Society for Clinical Pharmacology and Therapeutics, and the American Society of Clinical Oncology.

His current research interests focus on the role of solute carriers in anticancer drug disposition and toxicity, and his laboratory is funded by grants from the National Cancer Institute and the NIH.

Beyond transporters, he is interested in the Simon-Le Clerc controversy, and late-medieval polyphony (Machaut - Dufay), and cheese.

Clin Pharmacol Ther. 2022;In press. Transporters and toxicity: Insights from the International Transporter Consortium Workshop 4. Hafey MJ, Aleksunes LM, Bridges CC, Brouwer KR, Chien HC, Leslie EM, Hu S, Li Y, Shen J, Sparreboom A, Sprowl J, Tweedie D, Lai Y. PubMed

Pharmaceutics. 2022;14:694. Interaction of antifungal drugs with CYP3A- and OATP1B-mediated Venetoclax elimination. Eisenmann ED, Garrison DA, Talebi Z, Jin Y, Silvaroli JA, Kim JG, Sparreboom A, Savona MR, Mims AS, Baker SD. PubMed

Pharmaceutics. 2021;13:2004. In vitro and in vivo inhibition of MATE1 by Tyrosine Kinase Inhibitors. Uddin ME, Talebi Z, Chen S, Jin Y, Gibson AA, Noonan AM, Cheng X, Hu S, Sparreboom A. PubMed

Molecules. 2021;26:5500. Endogenous biomarkers for SLC transporter-mediated Drug-Drug Interaction evaluation. Li Y, Talebi Z, Chen X, Sparreboom A, Hu S. PubMed

Basic Clin Pharmacol Toxicol. 2021;In press. Contribution of membrane transporters to chemotherapy-induced cardiotoxicity. Uddin ME, Moseley A, Hu S, Sparreboom A. PubMed

Pharmaceutics. 2021;13:918. Imaging-based characterization of a Slco2b1(-/-) mouse model using [11C]Erlotinib and [99mTc]Mebrofenin as probe substrates. Marie S, Hernández-Lozano I, Breuil L, Truillet C, Hu S, Sparreboom A, Tournier N, Langer O. PubMed

Basic Clin Pharmacol Toxicol. 2021;In press. Boosting the oral bioavailability of anticancer drugs through intentional drug-drug interactions. Eisenmann ED, Talebi Z, Sparreboom A, Baker SD. PubMed

Front Pharmacol. 2021;12:644342. Influence of YES1 Kinase and Tyrosine Phosphorylation on the Activity of OCT1. Uddin ME, Garrison DA, Kim K, Jin Y, Eisenmann ED, Huang KM, Gibson AA, Hu Z, Sparreboom A, Hu S. PubMed

Clin Cancer Res. 2021;27:4301-4310. Regulation of OATP1B1 function by tyrosine kinase-mediated phosphorylation. Hayden E, Chen M, Pasquariello KZ, Gibson AA, Petti JJ, Shen S, Qu J, Ong SS, Chen T, Jin Y, Uddin ME, Huang KM, Paz A, Sparreboom A, Hu S, Sprowl JA. PubMed

Proc Natl Acad Sci U S A. 2021;118:e2020168118. Targeting OCT3 attenuates doxorubicin-induced cardiac injury. Huang KM, Zavorka Thomas M, Magdy T, Eisenmann ED, Uddin ME, DiGiacomo DF, Pan A, Keiser M, Otter M, Xia SH, Li Y, Jin Y, Fu Q, Gibson AA, Bonilla IM, Carnes CA, Corps KN, Coppola V, Smith SA, Addison D, Nies AT, Bundschuh R, Chen T, Lustberg MB, Wang J, Oswald S, Campbell MJ, Yan PS, Baker SD, Hu S, Burridge PW, Sparreboom A. PubMed

Clin Transl Sci2021;14:460-467. Role for drug transporters in chemotherapy-induced peripheral neuropathy. Stage TB, Hu S, Sparreboom A, Kroetz DL. PubMed

Pharmaceutics. 2020;12:856. Role of OATP1B1 and OATP1B3 in Drug-Drug interactions mediated by Tyrosine Kinase Inhibitors. Garrison DA, Talebi Z, Eisenmann ED, Sparreboom A, Baker SD. PubMed

Pharmaceutics. 2020;12:788. Influence of Probenecid on the pharmacokinetics and pharmacodynamics of Sorafenib. Hussaarts KGAM, van Doorn L, Eechoute K, Damman J, Fu Q, van Doorn N, Eisenmann ED, Gibson AA, Oomen-de Hoop E, de Bruijn P, Baker SD, Koolen SLW, van Gelder T, van Leeuwen RWF, Mathijssen RHJ, Sparreboom A, Bins S.  PubMed

J Clin Invest. 2020;130:4601-4606. Neuronal uptake transporters contribute to oxaliplatin neurotoxicity in mice. Huang KM, Leblanc AF, Uddin ME, Kim JY, Chen M, Eisenmann ED, Gibson A, Li Y, Hong KW, DiGiacomo D, Xia SH, Alberti P, Chiorazzi A, Housley SN, Cope TC, Sprowl JA, Wang J, Loprinzi CL, Noonan A, Lustberg M, Cavaletti G, Pabla N, Hu S, Sparreboom A. PubMed

Expert Opin Drug Metab Toxicol. 2020;16:493-506. Role of SLC transporters in toxicity induced by anticancer drugs. Huang KM, Uddin ME, DiGiacomo D, Lustberg MB, Hu S, Sparreboom A. PubMed

Drug Metab Dispos. 2020;48:419-425.  Role of Oatp2b1 in Drug Absorption and Drug-Drug Interactions. Chen M, Hu S, Li Y, Gibson AA, Fu Q, Baker SD, Sparreboom A. PubMed

Pharmacol Res Perspect. 2019;7:e00534. Role of equilibrative nucleoside transporter 1 (ENT1) in the disposition of cytarabine in mice. Anderson JT, Hu S, Fu Q, Baker SD, Sparreboom A. PubMed

CPT Pharmacometrics Syst Pharmacol. 2019;8:931-939. Predicting Paclitaxel disposition in humans with whole-body Physiologically-Based Pharmacokinetic Modeling. Fu Q, Sun X, Lustburg MB, Sparreboom A, Hu S. PubMed

Arch Toxicol. 2019;93:2835-2848. An integrative approach to cisplatin chronic toxicities in mice reveals importance of organic cation-transporter-dependent protein networks for renoprotection. Hucke A, Rinschen MM, Bauer OB, Sperling M, Karst U, Köppen C, Sommer K, Schröter R, Ceresa C, Chiorazzi A, Canta A, Semperboni S, Marmiroli P, Cavaletti G, Schlatt S, Schlatter E, Pavenstädt H, Heitplatz B, Van Marck V, Sparreboom A, Barz V, Knief A, Deuster D, Zehnhoff-Dinnesen AA, Ciarimboli G. PubMed

Clin Pharmacol Ther. 2020;107:227-237. Sorafenib activity and disposition in liver cancer does not depend on Organic Cation Transporter 1. Chen M, Neul C, Schaeffeler E, Frisch F, Winter S, Schwab M, Koepsell H, Hu S, Laufer S, Baker SD, Sparreboom A, Nies AT. PubMed

SLAS Discov. 2019;24:904-914. Identification of the tetraspanin CD9 as an interaction partner of Organic Cation Transporters 1 and 2. Snieder B, Brast S, Grabner A, Buchholz S, Schröter R, Spoden GA, Florin L, Salomon J, Albrecht T, Barz V, Sparreboom A, Ciarimboli G. PubMed

Clin Transl Sci. 2019;12:400-407. Interaction between sex and Organic Anion-Transporting Polypeptide 1b2 on the pharmacokinetics of Regorafenib and its metabolites Regorafenib-N-Oxide and Regorafenib-Glucuronide in mice. Fu Q, Chen M, Anderson JT, Sun X, Hu S, Sparreboom A, Baker SD. PubMed

Pharmacogenomics. 2018;19:883-888. Drug transporters and anthracycline-induced cardiotoxicity. Huang KM, Hu S, Sparreboom A. PubMed

J Chromatogr B Analyt Technol Biomed Life Sci. 2018;1090:43-51. Development and validation of an analytical method for regorafenib and its metabolites in mouse plasma. Fu Q, Chen M, Hu S, McElroy CA, Mathijssen RH, Sparreboom A, Baker SD. PubMed

J Clin Invest. 2018;128:816-825. OATP1B2 deficiency protects against paclitaxel-induced neurotoxicity. Leblanc AF, Sprowl JA, Alberti P, Chiorazzi A, Arnold WD, Gibson AA, Hong KW, Pioso MS, Chen M, Huang KM, Chodisetty V, Costa O, Florea T, de Bruijn P, Mathijssen RH, Reinbolt RE, Lustberg MB, Sucheston-Campbell LE, Cavaletti G, Sparreboom A, Hu S. PubMed

Clin Pharmacol Ther. 2017;102:726-730. Kinase inhibitors: The reality behind the success. Jeon JY, Sparreboom A, Baker SD. PubMed

Clin Transl Sci. 2017;10:412-420. Identification of OAT1/OAT3 as contributors to Cisplatin toxicity. Hu S, Leblanc AF, Gibson AA, Hong KW, Kim JY, Janke LJ, Li L, Vasilyeva A, Finkelstein DB, Sprowl JA, Sweet DH, Schlatter E, Ciarimboli G, Schellens J, Baker SD, Pabla N, Sparreboom A. PubMed

Clin Transl Sci. 2017;10:271-279. Influence of OATP1B1 Function on the Disposition of Sorafenib-β-D-Glucuronide. Bins S, van Doorn L, Phelps MA, Gibson AA, Hu S, Li L, Vasilyeva A, Du G, Hamberg P, Eskens F, de Bruijn P, Sparreboom A, Mathijssen R, Baker SD. PubMed

Cancer Res. 2017;77:2102-2111. OCTN1 Is a high-affinity carrier of nucleoside analogues. Drenberg CD, Gibson AA, Pounds SB, Shi L, Rhinehart DP, Li L, Hu S, Du G, Nies AT, Schwab M, Pabla N, Blum W, Gruber TA, Baker SD, Sparreboom A. PubMed

Trends Pharmacol Sci. 2016;37:904-932. Impact of membrane drug transporters on resistance to small-molecule tyrosine kinase inhibitors. Neul C, Schaeffeler E, Sparreboom A, Laufer S, Schwab M, Nies AT. PubMed

Clin Pharmacol Ther. 2016;100:398-403. Drug transporters: advances and opportunities. Govindarajan R, Sparreboom A. PubMed

Nat Commun. 2016;7:10880. A phosphotyrosine switch regulates organic cation transporters. Sprowl JA, Ong SS, Gibson AA, Hu S, Du G, Lin W, Li L, Bharill S, Ness RA, Stecula A, Offer SM, Diasio RB, Nies AT, Schwab, Cavaletti G, Schlatter E, Ciarimboli G, Schellens JH, Isacoff EY, Sali A, Chen T, Baker SD, Sparreboom A, Pabla N. PubMed

Clin Transl Sci. 2016;9:51-9. ABCC4 Is a determinant of cytarabine-induced cytotoxicity and myelosuppression. Drenberg CD, Hu S, Li L, Buelow DR, Orwick SJ, Gibson AA, Schuetz JD, Sparreboom A, Baker SD. PubMed

Mol Pharmacol. 2015;88:477-87. Lysosomal sequestration determines intracellular Imatinib levels. Burger H, den Dekker AT, Segeletz S, Boersma AW, de Bruijn P, Debiec-Rychter M, Taguchi T, Sleijfer S, Sparreboom A, Mathijssen RH, Wiemer EA. PubMed

Cancer Treat Rev. 2015;41:605-13. Inter-patient variability in docetaxel pharmacokinetics: A review. Nieuweboer AJ, de Morrée ES, de Graan AJ, Sparreboom A, de Wit R, Mathijssen RH. PubMed

Cancer Res. 2015;75:2729-36. Hepatocellular shuttling and recirculation of Sorafenib-glucuronide is dependent on Abcc2, Abcc3, and Oatp1a/1b. Vasilyeva A, Durmus S, Li L, Wagenaar E, Hu S, Gibson AA, Panetta JC, Mani S, Sparreboom A, Baker SD, Schinkel AH. PubMed

Proc Natl Acad Sci U S A. 2015;112:5231-6. Mitigation of acute kidney injury by cell-cycle inhibitors that suppress both CDK4/6 and OCT2 functions. Pabla N, Gibson AA, Buege M, Ong SS, Li L, Hu S, Du G, Sprowl JA, Vasilyeva A, Janke LJ, Schlatter E, Chen T, Ciarimboli G, Sparreboom A. PubMed

Pharmacogenomics. 2015;16:323-32. Human OCT2 variant c.808G>T confers protection effect against cisplatin-induced ototoxicity. Lanvers-Kaminsky C, Sprowl JA, Malath I, Deuster D, Eveslage M, Schlatter E, Mathijssen RH, Boos J, Jürgens H, Am Zehnhoff-Dinnesen AG, Sparreboom A, Ciarimboli G. PubMed

Clin Cancer Res. 2014;20:4167. Hepatic uptake transporters and docetaxel disposition in mice. Sparreboom A, Mathijssen RH. PubMed

Clin Cancer Res. 2014;20:4026-35.  Cisplatin-induced renal injury is independently mediated by OCT2 and p53. Sprowl JA, Lancaster CS, Pabla N, Hermann E, Kosloske AM, Gibson AA, Li L, Zeeh D, Schlatter E, Janke LJ, Ciarimboli G, Sparreboom A. PubMed

Cancer Res. 2014;74:3137-45. Influence of drug formulation on OATP1B-mediated transport of paclitaxel. Nieuweboer AJ, Hu S, Gui C, Hagenbuch B, Ghobadi Moghaddam-Helmantel IM, Gibson AA, de Bruijn P, Mathijssen RH, Sparreboom A. PubMed

Br J Cancer. 2014;110:894-8. Inhibition of OATP1B1 by tyrosine kinase inhibitors: in vitro-in vivo correlations. Hu S, Mathijssen RH, de Bruijn P, Baker SD, Sparreboom A. PubMed

Drug Metab Dispos. 2014;42:611-22. Uptake carriers and oncology drug safety. Sprowl JA, Sparreboom A. PubMed

Clin Cancer Res. 2014;20:985-94. Cellular uptake of imatinib into leukemic cells is independent of human organic cation transporter 1 (OCT1). Nies AT, Schaeffeler E, van der Kuip H, Cascorbi I, Bruhn O, Kneba M, Pott C, Hofmann U, Volk C, Hu S, Baker SD, Sparreboom A, Ruth P, Koepsell H, Schwab M. PubMed

Am J Physiol Cell Physiol. 2013;305:C1223-9. Epub 2013 Aug 28. Organic anion transporting polypeptide 1B transporters modulate hydroxyurea pharmacokinetics. Walker AL1, Lancaster CS, Finkelstein D, Ware RE, Sparreboom A. PubMed

Clin Pharmacol Ther. 2013;94:585-92. Conjunctive therapy of cisplatin with the OCT2 inhibitor cimetidine: influence on antitumor efficacy and systemic clearance. Sprowl JA, van Doorn L, Hu S, van Gerven L, de Bruijn P, Li L, Gibson AA, Mathijssen RH, Sparreboom A. PubMed

Clin Cancer Res. 2013;19:4359-70. Contribution of ABCC4-mediated gastric transport to the absorption and efficacy of dasatinib. Furmanski BD, Hu S, Fujita K, Li L, Gibson AA, Janke LJ, Williams RT, Schuetz JD, Sparreboom A, Baker SD. PubMed

Proc Natl Acad Sci USA. 2013;110:11199-204. Oxaliplatin-induced neurotoxicity is dependent on the organic cation transporter OCT2. Sprowl JA, Ciarimboli G, Lancaster CS, Giovinazzo H, Gibson AA, Du G, Janke LJ, Cavaletti G, Shields AF, Sparreboom A. PubMed

Blood. 2013;121:4965-6. Can "specific" OCT1 inhibitors be used to determine OCT1 transporter activity toward imatinib? Burger H, Mathijssen RH, Sparreboom A, Wiemer EA. PubMed

Mol Cancer Ther. 2013;12:1537-44. Modulation of OATP1B-type transporter function alters cellular uptake and disposition of platinum chemotherapeutics. Lancaster CS, Sprowl JA, Walker AL, Hu S, Gibson AA, Sparreboom A. PubMed

Clin Cancer Res. 2013;19:1458-66. Contribution of OATP1B1 and OATP1B3 to the disposition of sorafenib and sorafenib-glucuronide. Zimmerman EI, Hu S, Roberts JL, Gibson AA, Orwick SJ, Li L, Sparreboom A, Baker SD. PubMed

Drug Metab Pharmacokinet. 2013;28:19-27. Polymorphic transporters and platinum pharmacodynamics. Sprowl JA, Ness RA, Sparreboom A. PubMed

Clin Pharmacol Ther. 2012;92:531-4. Drug trafficking: recent advances in therapeutics and disease. Sprowl JA, Sparreboom A. PubMed

Clin Pharmacol Ther. 2012;92:642-50. OATP1B1 polymorphism as a determinant of erythromycin disposition. Lancaster CS, Bruun GH, Peer CJ, Mikkelsen TS, Corydon TJ, Gibson AA, Hu S, Orwick SJ, Mathijssen RH, Figg WD, Baker SD, Sparreboom A. PubMed

Clin Cancer Res. 2012;18:4433-40. Influence of polymorphic OATP1B-type carriers on the disposition of docetaxel. de Graan AJ, Lancaster CS, Obaidat A, Hagenbuch B, Elens L, Friberg LE, de Bruijn P, Hu S, Gibson AA, Bruun GH, Corydon TJ, Mikkelsen TS, Walker AL, Du G, Loos WJ, van Schaik RH, Baker SD, Mathijssen RH, Sparreboom A. PubMed

Clin Pharmacol Ther. 2012;91:1022-6. Associations between ABCC2 polymorphisms and cisplatin disposition and efficacy. Sprowl JA, Gregorc V, Lazzari C, Mathijssen RH, Loos WJ, Sparreboom A. PubMed

Drug Resist Updat. 2012;15:5-20. Contribution of tumoral and host solute carriers to clinical drug response. Sprowl JA, Mikkelsen TS, Giovinazzo H, Sparreboom A. PubMed

Genome Res. 2012;22:1-8. Rare versus common variants in pharmacogenetics: SLCO1B1 variation and methotrexate disposition. Ramsey LB, Bruun GH, Yang W, Treviño LR, Vattathil S, Scheet P, Cheng C, Rosner GL, Giacomini KM, Fan Y, Sparreboom A, Mikkelsen TS, Corydon TJ, Pui CH, Evans WE, Relling MV. PubMed

Clin Pharmacol Ther. 2011;89:816-20. Environmental and genetic factors affecting transport of imatinib by OATP1A2. Eechoute K, Franke RM, Loos WJ, Scherkenbach LA, Boere I, Verweij J, Gurney H, Kim RB, Tirona RG, Mathijssen RH, Sparreboom A. PubMed

Clin Pharmacol Ther. 2011;89:693-701. Effect of ABCC2 (MRP2) transport function on erythromycin metabolism. Franke RM, Lancaster CS, Peer CJ, Gibson AA, Kosloske AM, Orwick SJ, Mathijssen RH, Figg WD, Baker SD, Sparreboom A. PubMed