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The Role of the Constitutive Androstane Receptor in Cyclophosphamide-based Treatment of Lymphomas Item Type dissertation Authors Hedrich, William Dominic Publication Date 2018 Abstract Cyclophosphamide (CPA) is an alkylating prodrug which has been utilized extensively in combination chemotherapies for the treatment of cancers and autoimmune disorders since its introduction to the market in the late 1950s. The metabolic conversion o... Keywords constitutive androstane receptor; CYP2B6; drug-drug interactions; Cyclophosphamide; Cytochrome P-450 CYP2B6; Drug Interactions Download date 07/10/2021 19:53:39 Link to Item http://hdl.handle.net/10713/8006 William D. Hedrich Email: [email protected] EDUCATION: Degree Institution Field of Study Date Bachelor of The Pennsylvania State Toxicology 2013 Science University Bachelor of The Pennsylvania State Biology-Vertebrate 2013 Science University Physiology Doctor of University of Maryland, Pharmaceutical 2018 Philosophy Baltimore Sciences ______________________________________________________________________________ RESEARCH EXPERIENCE Graduate Research Assistant Wang Lab, University of Maryland School of Pharmacy • The role of the constitutive androstane receptor in cyclophosphamide-based treatment of lymphomas • Inductive expression of drug metabolizing enzymes and transporters in human primary hepatocytes • Metabolism-mediated drug-drug interactions • In-vivo tumor xenograft models Hassan Lab, University of Maryland School of Pharmacy • Pharmacokinetics of l-THP as an experimental therapy for cocaine addiction • In-vivo pharmacokinetics of l-THP and its major metabolites in rats • In-vivo drug-drug interactions of cocaine and synthetic opioids in rats • Pharmacokinetics of cyclophosphamide and its major metabolites in mice Undergraduate Research Assistant Omiecinski Lab, The Pennsylvania State University • Differential metabolism of polycyclic aromatic hydrocarbons by polymorphic microsomal epoxide hydrolase (EPX1) • Methylation profiles of CpG islands in the upstream promoter regions of the human microsomal epoxide hydrolase gene ______________________________________________________________________________ PUBLICATIONS • Hedrich, WD., Xiao, J. et al. (2016). “Activation of the Constitutive Androstane Receptor Increases the Therapeutic Index of CHOP in Lymphoma Treatment. Mol Cancer Ther 15(3): 392-401. • Hedrich, WD., Hassan, HE, Wang, H (2016). “Insights into CYP2B6-mediated drug-drug interactions”. Review. Acta Pharmaceutica Sinica B. 6(5): 413-425. • Hedrich, WD et al. “In vitro and in vivo characterization of levo- tetrahydropalmatine, a compound with anti-addictive properties: Gene induction, cytotoxicity, metabolism, pharmacokinetics, and drug-drug interaction studies.” Submitted to the International Journal of Pharmaceutics. • Hedrich, WD. et al. “Targeting transcription factors to improve CHOP-based treatment of lymphomas: Roles of CAR and Nrf2”. In preparation. • Gharavi, R. Hedrich, WD. et al. (2015). “Transporter-mediated Disposition of Opioids: Implications for Clinical Drug Interactions.” Review. Pharm Res 32(8):2477-502. • Hedrich, WD. et al. “Antibody Drug Conjugates: PK/PD Modeling, Preclinical Characterization, Clinical Studies, and Lessons Learned”. Clinical Pharmacokinetics. In press. • Hedrich, WD., et al. “Genotyping your own DNA in pharmacy education and personalized medicine”. Submitted to Currents in Pharmacy Teaching and Learning. • Zaw, MN., Munuhe, T., Hedrich, WD., et al. (2017) “Thermal Analysis of PDMS-Based Casting Proess with a 3D-Printed Mold”. Submitted to Applied Thermal Engineering. • Andar, A., Ram, K., Pecher, W. Hedrich, WD., et al. (2017) “Microneedle- Assisted Skin Permeation by Non-toxic Bioengineerable Gas Vesicle Nanoparticles”. Mol Pharmaceutics. In press. • Hedrich, WD. et al. “Administration of methadone and oxycodone alters the expression of drug metabolizing enzymes and transporters affecting the disposition of cocaine”. In preparation for submission to Molecular Pharmaceutics. ______________________________________________________________________________ PRESENTATIONS • William D. Hedrich, Linhao Li, Daochuan Li, Yuanfu Lu, Hazem E. Hassan, and Hongbing Wang. “Characterization of CITCO and Implications for Lymphoma Treatment”. Meeting of the American College of Clinical Pharmacology (ACCP). San Diego, CA. 2017. • William D. Hedrich, Linhao Li, Daochuan Li, Yuanfu Lu, Hazem E. Hassan, and Hongbing Wang. “Characterization of CITCO and Implications for Lymphoma Treatment”. Gordon Research Conference on Drug Metabolism. Holderness, NH. 2017. • William D. Hedrich, Linhao Li, Daochuan Li, Yuanfu Lu, Hazem E. Hassan, and Hongbing Wang. “Characterization of CITCO and Implications for Lymphoma Treatment”. Frontiers at the Chemistry-Biology Interface Symposium. University of Delaware. 2017. 2nd Place Best Poster Award. • William D. Hedrich, David S. Nakhla, Hongbing Wang, and Hazem E. Hassan. "Administration of methadone and oxycodone alters the expression of drug metabolizing enzymes and transporters affecting the disposition of cocaine." Annual meeting of the American Association of Pharmaceutical Scientists (AAPS). Denver, CO. 2016. Poster. PPDM Section Travel Award. • William D. Hedrich, Linhao Li, Scott Heyward, Maria R. Baer, Hazem E. Hassan, and Hongbing Wang. "Targeting the constitutive androstane receptor as a novel method for treating hematologic malignancies." Annual meeting of the American Association of Pharmaceutical Scientists (AAPS). Denver, CO. 2016. Poster. • William D. Hedrich, Linhao Li, Scott Heyward, Maria R. Baer, Hazem E. Hassan, and Hongbing Wang. "Targeting the constitutive androstane receptor as a novel method for treating hematologic malignancies". Meeting of the Globalization of Pharmaceutics Education Network (GPEN). Lawrence, KS. 2016. Oral presentation. • William D. Hedrich, Shamia L. Faison, Robert Gharavi, Hongbing Wang, Hazem E. Hassan, Jia Bei Wang. "Levo-tetrahydropalmatine does not affect the pharmacokinetics of concomitantly administered cocaine in rats." Annual Meeting of the American College of Clinical Pharmacology (ACCP). Bethesda, MD. 2016. Poster. • William D. Hedrich, Jingwei Xiao, Scott Heyward, Yao Zhang, Junran Zhang, Maria R. Baer, Hazem E. Hassan, and Hongbing Wang. “Combination of CHOP and an agonist of the constitutive androstane receptor increases the therapeutic index of lymphoma treatment”. Graduate Research Conference, University of Maryland, Baltimore 2016. Poster. Outstanding Presentation Award. • William D. Hedrich, Jingwei Xiao, Scott Heyward, Michael D. Mitchell, Hazem E. Hassan, and Hongbing Wang. “Activation of the constitutive androstane receptor increases the benefit-risk ratio of CHOP-based treatment of lymphomas. Annual Meeting of the International Society for the Study of Xenobiotics (ISSX), San Francisco, CA, October, 2014. Poster. • William D. Hedrich, Jingwei Xiao, Scott Heyward, Yao Zhang, Junran Zhang, Maria R. Baer, Hazem E. Hassan, and Hongbing Wang. “Combination of CHOP and an agonist of the constitutive androstane receptor increases the therapeutic index of lymphoma treatment”. Frontiers at the Chemistry-Biology Interface Symposium, Johns Hopkins University. 2016. Poster. INVITED TALKS • “Targeting the constitutive androstane receptor as a novel method for treating hematologic malignancies”. GPEN Conference. Cell culture models of pharmacokinetics short course. 2016. • “Targeting CAR as a novel method for treating hematologic malignancies.” University of Maryland School of Pharmacy Research Day. 2017. • “Impact of philanthropy on graduate student educations”. David Stewarts Associates Dinner. 2017. AWARDS AND HONORS • PhRMA Foundation Pre-doctoral Fellowship in Pharmacology/Toxicology. 2017. • University of Maryland President’s Entrepreneurial Fellow. 2016-2017. • Department of Pharmaceutical Sciences Graduate Student Fellowship and Merit Award. 2016-2017. • Graduate Student Travel Award. Meeting of the American College of Clinical Pharmacology (ACCP). San Diego, CA. 2017. • 2nd Place Best Poster. Frontiers at the Chemistry/Biology Interface Symposium. University of Delaware. 2017. • AAPS PPDM Section Travel Award. Annual meeting of the American Association of Pharmaceutical Scientists (AAPS). Denver, CO. 2016. • Outstanding Presentation Award. Graduate Research Conference. University of Maryland, Baltimore. Baltimore, MD. 2016. ______________________________________________________________________________ EXTRACURRICULAR AFFILIATIONS • Graduate Student Representative, SOP Assessment Committee 2016-present • President, Pharmacy Graduate Student Association 2015-2016 • Vice President, Pharmacy Graduate Student Association 2014-2015 • First-Year Representative, Pharmacy Graduate Student Association 2013-2014 Abstract Title of Dissertation The Role of the Constitutive Androstane Receptor in Cyclophosphamide-based Treatment of Lymphomas Author William D. Hedrich, PhD Candidate, 2018 Dissertation Directed by: Hongbing Wang, PhD Professor and Program Chair University of Maryland School of Pharmacy Department of Pharmaceutical Sciences Hazem E. Hassan, PhD, MS, RCDS, RPh Assistant Professor and Director Pharmacokinetics and Biopharmaceutics Laboratory University of Maryland School of Pharmacy Department of Pharmaceutical Sciences Cyclophosphamide (CPA) is an alkylating prodrug which has been utilized extensively in combination chemotherapies for the treatment of cancers and autoimmune disorders since its introduction to the market in the late 1950s. The metabolic
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  • Supplementary Table S4. FGA Co-Expressed Gene List in LUAD

    Supplementary Table S4. FGA Co-Expressed Gene List in LUAD

    Supplementary Table S4. FGA co-expressed gene list in LUAD tumors Symbol R Locus Description FGG 0.919 4q28 fibrinogen gamma chain FGL1 0.635 8p22 fibrinogen-like 1 SLC7A2 0.536 8p22 solute carrier family 7 (cationic amino acid transporter, y+ system), member 2 DUSP4 0.521 8p12-p11 dual specificity phosphatase 4 HAL 0.51 12q22-q24.1histidine ammonia-lyase PDE4D 0.499 5q12 phosphodiesterase 4D, cAMP-specific FURIN 0.497 15q26.1 furin (paired basic amino acid cleaving enzyme) CPS1 0.49 2q35 carbamoyl-phosphate synthase 1, mitochondrial TESC 0.478 12q24.22 tescalcin INHA 0.465 2q35 inhibin, alpha S100P 0.461 4p16 S100 calcium binding protein P VPS37A 0.447 8p22 vacuolar protein sorting 37 homolog A (S. cerevisiae) SLC16A14 0.447 2q36.3 solute carrier family 16, member 14 PPARGC1A 0.443 4p15.1 peroxisome proliferator-activated receptor gamma, coactivator 1 alpha SIK1 0.435 21q22.3 salt-inducible kinase 1 IRS2 0.434 13q34 insulin receptor substrate 2 RND1 0.433 12q12 Rho family GTPase 1 HGD 0.433 3q13.33 homogentisate 1,2-dioxygenase PTP4A1 0.432 6q12 protein tyrosine phosphatase type IVA, member 1 C8orf4 0.428 8p11.2 chromosome 8 open reading frame 4 DDC 0.427 7p12.2 dopa decarboxylase (aromatic L-amino acid decarboxylase) TACC2 0.427 10q26 transforming, acidic coiled-coil containing protein 2 MUC13 0.422 3q21.2 mucin 13, cell surface associated C5 0.412 9q33-q34 complement component 5 NR4A2 0.412 2q22-q23 nuclear receptor subfamily 4, group A, member 2 EYS 0.411 6q12 eyes shut homolog (Drosophila) GPX2 0.406 14q24.1 glutathione peroxidase