Researchers in the Ami Shah Lab study scleroderma and Raynaud’s phenomenon. We examine the rela...tionship between cancer and scleroderma, with a focus on how and if cancer causes scleroderma to develop in some patients. We are currently conducting clinical research to study ways to detect cardiopulmonary complications in patients with scleroderma, biological and imaging markers of Raynaud’s phenomenon, and drugs that improve aspects of scleroderma. view more

Research in the Caleb Alexander Lab examines prescription drug use. This includes studies of po...pulation-based patterns and determinants of pharmaceutical use, clinical decision-making about prescription drugs, and the effect of changes in regulatory and payment policies on pharmaceutical utilization. We have special expertise in conducting survey-based studies and analyzing secondary data sources, including administrative claims, the Medical Expenditure Panel Survey and the National Ambulatory Medical Care Survey. view more

A. Laboratory activities include the use of accelerator mass spectrometry (AMS) techniques to m...easure 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 pharmacokinetics. 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

Research in the Craig W. Hendrix Lab concentrates on the chemoprevention of HIV infection, clin...ical pharmacology of antiviral drugs, drug interactions, and oral, topical and injectable HIV microbicide development. Our lab conducts small, intensive sampling studies of PK and PD of drugs for HIV prevention with a focus on developing methods to better understand HIV and drug distribution in the male genital tract, female genital tract and lower gastrointestinal tract. We also support numerous HIV pre-exposure prophylaxis development studies from phase I to phase III, largely as leader of the Pharmacology Core Laboratory of both the Microbicide Trial Network and HIV Prevention Trials Network. view more

The Dölen lab studies the synaptic and circuit mechanisms that enable social behaviors. We use ...a variety of techniques including whole cell patch clamp electrophysiology, viral mediated gene transfer, optogenetics, and behavior. We are also interested in understanding how these synaptic and circuit mechanisms are disrupted in autism and schizophrenia, diseases which are characterized by social cognition deficits. More recently we have become interested in the therapeutic potential of psychedelic drugs for diseases like addiction and PTSD that respond to social influence or are aggravated by social injury, We are currently using both transgenic mouse and octopus to model disease. view more

Research in the Eric Nuermberger Lab focuses primarily on experimental chemotherapy for tubercu...losis. We use proven murine models of active and latent tuberculosis infection to assess the effectiveness of novel antimicrobials. A key goal is to identify new agents to combine with existing drugs to shorten tuberculosis therapy or enable less frequent drug administration. We're also using a flow-controlled in vitro pharmacodynamic system to better understand the pharmacodynamics of drug efficacy and the selection of drug-resistant mutants during exposure to current agents. view more

The Frueh Laboratory uses nuclear magnetic resonance (NMR) to study how protein dynamics can be... modulated and how active enzymatic systems can be conformed. Non-ribosomal peptide synthetases (NRPS) are large enzymatic systems that biosynthesize secondary metabolites, many of which are used by pharmaceutical scientists to produce drugs such as antibiotics or anticancer agents. Dr. Frueh's laboratory uses NMR to study inter- and intra-domain modifications that occur during the catalytic steps of NRPS. Dr. Frueh and his team are constantly developing new NMR techniques to study these complicated enzymatic systems. view more

Human induced pluripotent stem cells (hiPSCs) provide unprecedented opportunities for cell repl...acement approaches, disease modeling and drug discovery in a patient-specific manner. The Gabsang Lee Lab focuses on the neural crest lineage and skeletal muscle tissue, in terms of their fate-determination processes as well as relevant genetic disorders.

Previously, we studied a human genetic disorder (familial dysautonomia, or FD) with hiPSCs and found that FD-specific neural crest cells have low levels of genes needed to make autonomous neurons--the ones needed for the "fight-or-flight" response. In an effort to discover novel drugs, we performed high-throughput screening with a compound library using FD patient-derived neural crest cells.

We recently established a direct conversion methodology, turning patient fibroblasts into "induced neural crest (iNC)" that also exhibit disease-related phenotypes, just as the FD-hiPSC-derived neural crest. We're extending our research to the neural crest's neighboring cells, somite. Using multiple genetic reporter systems, we identified sufficient cues for directing hiPSCs into somite stage, followed by skeletal muscle lineages. This novel approach can straightforwardly apply to muscular dystrophies, resulting in expandable myoblasts in a patient-specific manner.
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Intestinal chloride secretion is stimulated during diarrhea. Cholera toxin is secreted by bacte...rium Vibrio cholera and is responsible for the watery diarrhea after cholera infection. Mechanistically, cholera toxin increases intracellular cyclic AMP, which subsequently activates protein kinase A and the cystic fibrosis transmembrane regulator chloride channel (CFTR).

However, we recently identified an intestinal cAMP-Ca cross-talk signaling pathway that is initiated by elevation of intracellular cAMP and subsequently elevates intracellular Ca concentrations through the exchange protein activated by cAMP (Epac). This observation suggests that both CFTR and calcium-activated chloride channels are targets of elevated intracellular cAMP signaling molecule.

Therefore, we are studying the role of calcium-activated Cl channels in intestinal chloride secretion under physiological conditions and during diarrhea. We are also determining whether the recently identified transmembrane protein 16 family of proteins, which are calcium-activated chloride channels, is also involved in intestinal chloride secretion in addition to the well characterized CFTR channel.

Increased understanding of regulation of intestinal Cl secretion provides the necessary background information for the development of therapeutic drugs for the treatment of diarrhea, constipation and cystic fibrosis. The discovery that calcium-activated chloride channels are involved in intestinal chloride secretion provides additional targets for anti-diarrhea drug development. view more

Research in the Jodi Segal Lab focuses on developing methodologies to use observational data to... understand the use of new drugs, particularly drugs for treating diabetes, blood disorders and osteoporosis. We apply advanced methods for evidence-based review and meta-analysis, and—in collaboration with Johns Hopkins biostatisticians—we have developed new methodologies for observational research (using propensity scores to adjust for covariates that change over time) and methods to account for competing risks and heterogeneity of treatment effects in analyses. view more