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BCMBJHU SOM

Faculty & Research

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Namandje' N. Bumpus

Department Affiliation Primary: Pharmacology
Secondary: Medicine
RankAssistant Professor
Phone Numbers410-955-0562
Fax: 410-614-9978
Emailnbumpus1@jhmi.edu
School of Medicine Address725 N. Wolfe Street
Biophysics 307A
Baltimore MD 21205
Link to Lab Homepage
Namandje' N. Bumpus

Research Topic: Role of drug metabolism in non-nucleoside reverse transcriptase inhibitor-mediated toxicity.

Our laboratory uses mass spectrometry and molecular pharmacology based approaches to investigate the biotransformation of clinically used drugs by the cytochromes P450s. The cytochromes P450 are crucial to drug disposition as they are responsible for the metabolism of an estimated 75% of currently marketed drugs. Cytochrome P450-mediated biotransformation of drugs most often results in the production of hydrophilic metabolites that can be readily excreted from the body; however, in certain instances toxic metabolites are formed that can stimulate cell death and organ failure. Research in our laboratory focuses on defining a role for cytochrome P450-dependent metabolites in the drug-induced acute liver failure that is associated with certain antiviral drugs used to treat HIV and hepatitis C. To approach this, we develop novel mass spectrometry assays to measure and discover drug metabolites. In addition, we isolate these metabolites and probe their pharmacology and toxicology using both in vitro and in vivo models. In doing so, we examine modulation of cellular signaling pathways by these metabolites using molecular techniques and mass spectrometry-based metabolomics to spur discovery of biomarkers and novel therapeutic targets for drug-induced liver failure. Further, once we have elucidated the chemical structure of a toxic metabolite we test whether blocking the site of metabolism can abrogate the toxicity without altering the pharmacologic activity of the drug. The long-term goal of our laboratory is gain information that can be used to develop next generation therapies that are devoid of these toxic events by preventing the formation of a toxic metabolite and/or by developing strategies for preventing toxicity using concomitant therapy.

Publications:

Hendrix C, Chen BA, Guddera V, Hoesley C, Justman J, Nakabiito C, Salata R, Soto-Torres L, Patterson K, Minnis AA, Gandham S, Gomez K, Richardson BA and Bumpus NN. 2013. MTN-001: Randomized pharmacokinetic cross-over study comparing tenofovir vaginal gel and oral tablets in vaginal tissue and other compartments. PLoS One 8(1):e55013.
PubMed Reference

Yanakakis LJ and Bumpus NN. 2012. Biotransformation of the antiretroviral drug etravirine: metabolite identification, reaction phenotyping and characterization of autoinduction of cytochrome P450-dependent metabolism. Drug Metabolism and Disposition 40(4):803-14.
PubMed Reference

Lu Y, Hendrix CW and Bumpus NN. 2012. Cytochrome P450 3A5 Plays a Prominent Role in the Oxidative Metabolism of the Anti-HIV Drug Maraviroc. Drug Metabolism and Disposition 40(12):2221-30.
PubMed Reference

Avery LB, VanAusdall JL, Hendrix CW and Bumpus NN. 2012. Compartmentalization and Antiviral Effect of Efavirencz Metabolites in Blood Plasma, Seminal Plasma and Cerebrospinal Fluid. Drug Metabolism and Disposistion. 41(2):422-9.
PubMed Reference

Bumpus NN. 2011. Efavirenz and 8-hydroxyefavirenz induce cell death via a JNK- and BimEL-dependent mechanism in primary human hepatocytes. Toxicology and Applied Pharmacology 257(2):227-34.
PubMed Reference ​

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