Research Summary

The focus of my laboratory is to understand the genetic basis of drug response and toxicity. Relevant to the Cancer Center are our efforts related to taxane-induced sensory peripheral neuropathy. I was trained as a clinical and molecular pharmacologist and have been involved in pharmacogenetics research for many years. I was an investigator on the Pharmacogenetics of Membrane Transporters project, part of the NIH-sponsored Pharmacogenetics Research Network (PGRN), from 2000-2015, focusing largely on pharmacogenomics of multidrug resistance transporters. Our current focus is on taxane-induced peripheral neuropathy. We use state-of-the-art genomic approaches, such as genome-wide genotyping and next-generation sequencing, to identify genetic biomarkers of drug toxicity and response. Clinical samples largely come from studies within the CALGB/Alliance clinical trial group. Functional genomic studies use cellular systems and model organisms to functionally characterize genetic variants of interest. Collaborative efforts are also ongoing to understand the molecular basis of variability in response to HDAC inhibitors.

Research Funding

  • October 1, 2019 - September 30, 2022 - The Role of Genomics in Postoperative Delirium and Sedation, Co-investigator leading the genomic analyses. Sponsor: NIH/NINR, Sponsor Award ID: R01 NR017622
  • July 1, 2017 - June 30, 2022 - Developing Silastic-Silicone for the Local Delivery of Hormonal Therapy to Prevent and Treat Breast Cancer, Co-Investigator. Sponsor: NIH/NCI, Sponsor Award ID: R01 CA220131
  • July 1, 1982 - June 30, 2022 - Pharmaceutical Sciences and Pharmacogenomics, Principal Investigator. Sponsor: NIH/NIGMS, Sponsor Award ID: T32 GM007175-41
  • July 1, 2015 - June 30, 2021 - Pharmacogenomics of Microtubule Targeting Agents, Principal Investigator. Sponsor: NIH, Sponsor Award ID: R01 CA192156-01A1

Education

Ohio State University, Columbus, OH, B.S., 1985, Pharmacy
University of Washington, Seattle, WA, Ph.D., 1990, Pharmaceutics
National Cancer Institute, Bethesda, MD, 1990-1993, Drug Metabolism

Honors & Awards

  • 1985
    Eli Lilly Co. Achievement Award
  • 1985
    Ohio State University Presidential Scholar
  • 1990
    Intramural Research Training Award Fellowship
  • 1991-1993
    Pharmacology Research Associate Fellowship
  • 1995
    Josephine Sitterle Failer Alumni Award, Ohio State University College of Pharmacy
  • 1996
    American Association of Pharmaceutical Sciences New Investigator Award in Pharmacokinetics, Pharmacodynamics and Drug Metabolism
  • 2002
    American Society for Clinical Pharmacology and Therapeutics Leon Goldberg Young Investigator Award
  • 2008
    Elected Fellow, American Association of Pharmaceutical Scientists

Selected Publications

  1. Xiong C, Chua KC, Stage TB, Priotti J, Kim J, Altman-Merino A, Chan D, Saraf K, Canato Ferracini A, Fattahi F, Kroetz DL. Human Induced Pluripotent Stem Cell Derived Sensory Neurons are Sensitive to the Neurotoxic Effects of Paclitaxel. Clin Transl Sci. 2021 03; 14(2):568-581.  View on PubMed
  2. Ferracini AC, Lopes-Aguiar L, Lourenço GJ, Yoshida A, Lima CSP, Sarian LO, Derchain S, Kroetz DL, Mazzola PG. GSTP1 and ABCB1 Polymorphisms Predicting Toxicities and Clinical Management on Carboplatin and Paclitaxel-Based Chemotherapy in Ovarian Cancer. Clin Transl Sci. 2021 03; 14(2):720-728.  View on PubMed
  3. Stage TB, Hu S, Sparreboom A, Kroetz DL. Role for Drug Transporters in Chemotherapy-Induced Peripheral Neuropathy. Clin Transl Sci. 2021 03; 14(2):460-467.  View on PubMed
  4. Chua KC, Xiong C, Ho C, Mushiroda T, Jiang C, Mulkey F, Lai D, Schneider BP, Rashkin SR, Witte JS, Friedman PN, Ratain MJ, McLeod HL, Rugo HS, Shulman LN, Kubo M, Owzar K, Kroetz DL. Genomewide Meta-Analysis Validates a Role for S1PR1 in Microtubule Targeting Agent-Induced Sensory Peripheral Neuropathy. Clin Pharmacol Ther. 2020 09; 108(3):625-634.  View on PubMed
  5. Stage TB, Mortensen C, Khalaf S, Steffensen V, Hammer HS, Xiong C, Nielsen F, Poetz O, Svenningsen ÅF, Rodriguez-Antona C, Kroetz DL. P-Glycoprotein Inhibition Exacerbates Paclitaxel Neurotoxicity in Neurons and Patients With Cancer. Clin Pharmacol Ther. 2020 09; 108(3):671-680.  View on PubMed
  6. Levy ES, Samy KE, Lamson NG, Whitehead KA, Kroetz DL, Desai TA. Reversible inhibition of efflux transporters by hydrogel microdevices. Eur J Pharm Biopharm. 2019 Dec; 145:76-84.  View on PubMed
  7. Li Z, Lin J, Sibley AB, Truong T, Chua KC, Jiang Y, McCarthy J, Kroetz DL, Allen A, Owzar K. Efficient estimation of grouped survival models. BMC Bioinformatics. 2019 May 28; 20(1):269.  View on PubMed
  8. Yee SW, Giacomini MM, Shen H, Humphreys WG, Horng H, Brian W, Lai Y, Kroetz DL, Giacomini KM. Organic Anion Transporter Polypeptide 1B1 Polymorphism Modulates the Extent of Drug-Drug Interaction and Associated Biomarker Levels in Healthy Volunteers. Clin Transl Sci. 2019 07; 12(4):388-399.  View on PubMed
  9. Jayagopal A, Brakeman PR, Soler P, Ferrell N, Fissell W, Kroetz DL, Roy S. Apical Shear Stress Enhanced Organic Cation Transport in Human OCT2/MATE1-Transfected Madin-Darby Canine Kidney Cells Involves Ciliary Sensing. J Pharmacol Exp Ther. 2019 06; 369(3):523-530.  View on PubMed
  10. Zakinova A, Long-Boyle JR, French D, Croci R, Wilson L, Phillips KA, Kroetz DL, Shin J, Tamraz B. A Practical First Step Using Needs Assessment and a Survey Approach to Implementing a Clinical Pharmacogenomics Consult Service. J Am Coll Clin Pharm. 2019 Jun; 2(3):214-221.  View on PubMed
  11. Rashkin SR, Chua KC, Ho C, Mulkey F, Jiang C, Mushiroda T, Kubo M, Friedman PN, Rugo HS, McLeod HL, Ratain MJ, Castillos F, Naughton M, Overmoyer B, Toppmeyer D, Witte JS, Owzar K, Kroetz DL. A Pharmacogenetic Prediction Model of Progression-Free Survival in Breast Cancer using Genome-Wide Genotyping Data from CALGB 40502 (Alliance). Clin Pharmacol Ther. 2019 03; 105(3):738-745.  View on PubMed
  12. Bartelink IH, Jones EF, Shahidi-Latham SK, Lee PRE, Zheng Y, Vicini P, van 't Veer L, Wolf D, Iagaru A, Kroetz DL, Prideaux B, Cilliers C, Thurber GM, Wimana Z, Gebhart G. Tumor Drug Penetration Measurements Could Be the Neglected Piece of the Personalized Cancer Treatment Puzzle. Clin Pharmacol Ther. 2019 07; 106(1):148-163.  View on PubMed
  13. Chang JL, Lee SA, Tsai AC, Musinguzi N, Muzoora C, Bwana B, Boum Y, Haberer JE, Hunt PW, Martin J, Bangsberg DR, Kroetz DL, Siedner MJ. CYP2B6 Genetic Polymorphisms, Depression, and Viral Suppression in Adults Living with HIV Initiating Efavirenz-Containing Antiretroviral Therapy Regimens in Uganda: Pooled Analysis of Two Prospective Studies. AIDS Res Hum Retroviruses. 2018 11; 34(11):982-992.  View on PubMed
  14. Li M, Mulkey F, Jiang C, O'Neil BH, Schneider BP, Shen F, Friedman PN, Momozawa Y, Kubo M, Niedzwiecki D, Hochster HS, Lenz HJ, Atkins JN, Rugo HS, Halabi S, Kelly WK, McLeod HL, Innocenti F, Ratain MJ, Venook AP, Owzar K, Kroetz DL. Identification of a Genomic Region between SLC29A1 and HSP90AB1 Associated with Risk of Bevacizumab-Induced Hypertension: CALGB 80405 (Alliance). Clin Cancer Res. 2018 10 01; 24(19):4734-4744.  View on PubMed
  15. Eclov RJ, Kim MJ, Smith R, Ahituv N, Kroetz DL. Rare Variants in the ABCG2 Promoter Modulate In Vivo Activity. Drug Metab Dispos. 2018 05; 46(5):636-642.  View on PubMed
  16. Sucheston-Campbell LE, Clay-Gilmour AI, Barlow WE, Budd GT, Stram DO, Haiman CA, Sheng X, Yan L, Zirpoli G, Yao S, Jiang C, Owzar K, Hershman D, Albain KS, Hayes DF, Moore HC, Hobday TJ, Stewart JA, Rizvi A, Isaacs C, Salim M, Gralow JR, Hortobagyi GN, Livingston RB, Kroetz DL, Ambrosone CB. Genome-wide meta-analyses identifies novel taxane-induced peripheral neuropathy-associated loci. Pharmacogenet Genomics. 2018 02; 28(2):49-55.  View on PubMed
  17. Stage TB, Graff M, Wong S, Rasmussen LL, Nielsen F, Pottegård A, Brøsen K, Kroetz DL, Khojasteh SC, Damkier P. Dicloxacillin induces CYP2C19, CYP2C9 and CYP3A4 in vivo and in vitro. Br J Clin Pharmacol. 2018 03; 84(3):510-519.  View on PubMed
  18. Stage TB, Bergmann TK, Kroetz DL. Clinical Pharmacokinetics of Paclitaxel Monotherapy: An Updated Literature Review. Clin Pharmacokinet. 2018 01; 57(1):7-19.  View on PubMed
  19. Eclov RJ, Kim MJ, Chhibber A, Smith RP, Ahituv N, Kroetz DL. ABCG2 regulatory single-nucleotide polymorphisms alter in vivo enhancer activity and expression. Pharmacogenet Genomics. 2017 Dec; 27(12):454-463.  View on PubMed
  20. Li M, Kroetz DL. Bevacizumab-induced hypertension: Clinical presentation and molecular understanding. Pharmacol Ther. 2018 02; 182:152-160.  View on PubMed

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