A. Laboratory activities include the use of accelerator mass spectrometry (AMS) techniques to measure intracellular drugs and drugs metabolites. AMS is a highly sensitive method for detecting tracer amounts of radio-labeled molecules in cells, tissues, and body fluids. We have been able to measure intracellular zidovudine triphosphate (the active anabolite of zidovudine) in peripheral blood mononuclear cells from healthy volunteers given small doses of 14C-zidovudine, and have directly compared the sensitivity of AMS to traditional LC/MS methods carried out in our laboratory.
B. Clinical research activities investigate the clinical pharmacology of new anti-HIV therapies and drug combinations. Specific drug classes studied include HIV reverse transcriptase inhibitors, protease inhibitors, entry inhibitors (selective CCR5 and CXCR4 antagonists), and integrase inhibitors. Scientific objectives of clinical studies include characterization of early drug activity, toxicity, and pharmacok...inetics. Additional objectives are characterization of pathways of drug metabolism, and identification of clinically significant harmful and beneficial drug interactions mediated by hepatic and intestinal cytochrome P450 isoforms.view more
Barbara Slusher, M.A.S., Ph.D., leads a 20-member veteran drug discovery team of medicinal chemists, assay developers, pharmacologists, toxicologists and pharmacokinetic/drug metabolism experts, who identify novel drug targets arising from JHU faculty’s research and translate them into new, small molecule drug therapies.
Her team collaborates extensively with faculty at the Bloomberg~Kimmel Institute for Cancer Immunotherapy and leads the BKI immunotherapy drug discovery core, aimed at developing new immune-targeting drug therapies for laboratory and clinical testing at Johns Hopkins.
The Bumpus Laboratory uses mass spectrometry and molecular pharmacology-based approaches to study the biotransformation of clinically used drugs by the cytochromes P450s. Specifically, we are studying ways to define 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. Our long-term goal is to gain information that can be used to develop therapies that are devoid of toxic events by preventing the formation of a toxic metabolite or by developing strategies for preventing toxicity using concomitant therapy.