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  • Advanced Optics Lab

    The Advanced Optics Lab uses innovative optical tools, including laser-based nanotechnologies, to understand cell motility and the regulation of cell shape. We pioneered laser-based nanotechnologies, including optical tweezers, nanotracking, and laser-tracking microrheology. Applications range from physics, pharmaceutical delivery by phagocytosis (cell and tissue engineering), bacterial pathogens important in human disease and cell division.

    Other projects in the lab are related to microscopy, specifically combining fluorescence and electron microscopy to view images of the subcellular structure around proteins.

    Research Areas: optics, microscopy, physics, cellular biology, imaging, nanotechnology, drugs, tissue engineering

    Lab Website

    Principal Investigator

    Scot Kuo, Ph.D.

    Department

    Biomedical Engineering

  • Ami Shah Lab

    Researchers in the Ami Shah Lab study scleroderma and Raynaud’s phenomenon. We examine the relationship 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.

    Research Areas: Raynaud's phenomenon, cancer, scleroderma, drugs, cardiovascular diseases

    Lab Website

    Principal Investigator

    Ami Shah, M.D.

    Department

    Medicine

  • Anderson Lab

    Research in the Anderson laboratory focuses on cellular signaling and ionic mechanisms that cause heart failure, arrhythmias and sudden cardiac death, major public health problems worldwide. Primary focus is on the multifunctional Ca2+ and calmodulin-dependent protein kinase II (CaMKII). The laboratory identified CaMKII as an important pro-arrhythmic and pro-cardiomyopathic signal, and its studies have provided proof of concept evidence motivating active efforts in biotech and the pharmaceutical industry to develop therapeutic CaMKII inhibitory drugs to treat heart failure and arrhythmias.

    Under physiological conditions, CaMKII is important for excitation-contraction coupling and fight or flight increases in heart rate. However, myocardial CaMKII is excessively activated during disease conditions where it contributes to loss of intracellular Ca2+ homeostasis, membrane hyperexcitability, premature cell death, and hypertrophic and inflammatory transcription. These downstream targets a...ppear to contribute coordinately and decisively to heart failure and arrhythmias. Recently, researchers developed evidence that CaMKII also participates in asthma.

    Efforts at the laboratory, funded by grants from the National Institutes of Health, are highly collaborative and involve undergraduate assistants, graduate students, postdoctoral fellows and faculty. Key areas of focus are:
    • Ion channel biology and arrhythmias
    • Cardiac pacemaker physiology and disease
    • Molecular physiology of CaMKII
    • Myocardial and mitochondrial metabolism
    • CaMKII and reactive oxygen species in asthma

    Mark Anderson, MD, is the William Osler Professor of Medicine, the director of the Department of Medicine in the Johns Hopkins University School of Medicine and physician-in-chief of The Johns Hopkins Hospital.
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    Research Areas: heart failure, arrhythmia, cardiovascular diseases, sudden cardiac death

    Lab Website

    Principal Investigator

    Mark Anderson, M.D., Ph.D.

    Department

    Medicine

  • Brady Maher Laboratory

    The Brady Maher Laboratory is interested in understanding the cellular and circuit pathophysiology that underlies neurodevelopmental and psychiatric disorders. Our lab focuses on trying to understand the function of genes that are associated with neurodevelopment problems by manipulating their expression level in utero during the peak of cortical development. We then use a variety of approaches and technologies to identify resulting phenotypes and molecular mechanisms including cell and molecular biology, optogenetics, imaging and electrophysiology.

    Current projects in the lab are focused on understanding the function of transcription factor 4 (TCF4), a clinically pleiotropic gene. Genome-wide association studies have identified genetic variants of TCF4 that are associated with schizophrenia, while autosomal dominant mutations in TCF4 result in Pitt Hopkins syndrome. Using our model system, we have identified several interesting electrophysiological and cell biological phenotypes as...sociated with altering the expression of TCF4 in utero. We hypothesize that these phenotypes represent cellular pathophysiology related to these disorders and by understanding the molecular mechanisms responsible for these phenotypes we expect to identify therapeutic targets for drug development.
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    Research Areas: cell biology, neurodevelopment, imaging, schizophrenia, psychiatric disorders, Pitt Hopkins syndrome, elecrophysiology, genomics, drugs, optogenetics, molecular biology, phenotypes

  • Caleb Alexander Lab

    Research in the Caleb Alexander Lab examines prescription drug use. This includes studies of population-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.

    Research Areas: epidemiology, medical decision making, drug safety, patient-provider relationships, pharmacoepidemiology, drugs

    Lab Website

    Principal Investigator

    G Alexander, M.D.

    Department

    Medicine

  • Center for Nanomedicine

    The Center for Nanomedicine engineers drug and gene delivery technologies that have significant implications for the prevention, treatment and cure of many major diseases facing the world today. Specifically, we are focusing on the eye, central nervous system, respiratory system, women's health, gastrointestinal system, cancer, and inflammation.

    We are a unique translational nanotechnology effort located that brings together engineers, scientists and clinicians working under one roof on translation of novel drug and gene delivery technologies

    Research Areas: central nervous system, respiratory system, nanotechnology, cancer, drugs, women's health, inflammation, eye, gastrointestinal

    Lab Website

    Principal Investigator

    Justin Hanes, Ph.D.

    Department

    Ophthalmology

  • Charles W. Flexner Laboratory

    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

    Research Areas: antiretroviral drugs, infectious disease, HIV protease inhibitors, HIV, drugs, accelerator mass spectrometry

    Principal Investigator

    Charles Flexner, M.D.

    Department

    Medicine

  • Craig W. Hendrix Lab

    Research in the Craig W. Hendrix Lab concentrates on the chemoprevention of HIV infection, clinical 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.

    Research Areas: antiretroviral therapies, infectious disease, HIV, drugs

    Principal Investigator

    Craig W. Hendrix, M.D.

    Department

    Medicine

  • Dölen Lab

    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.

    Research Areas: autism, PTSD, LSD, social behavior, Oxytocin, MDMA, neuroscience, psychedelics

    Lab Website

    Principal Investigator

    Gul Dolen, M.D., Ph.D.

    Department

    Neuroscience

  • Dolores Njoku Lab

    Research in the Dolores Njoku Lab focuses on immune-mediated liver injury caused by drugs such as anti-seizure medications and antibiotics. We use an animal model to understand the pathways involved in the injury process, recognizing that this model can also uncover pathways involved with other drugs that cause similar liver injury. We hope to uncover the immunogenic epitopes, or pieces, of the proteins that trigger the autoimmune reaction and identify the key regulatory pathways involved.

    Research Areas: anesthesia, antibiotics, liver injury, liver diseases, mouse models

  • Elizabeth M. Jaffee, M.D.

    Current projects include:

    The evaluation of mechanisms of immune tolerance to cancer in mouse models of breast and pancreatic cancer. We have characterized the HER-2/neu transgenic mouse model of spontaneous mammary tumors.
    This model demonstrates immune tolerance to the HER-2/neu gene product. This model is being used to better understand the mechanisms of tolerance to tumor. In addition, this model is being used to develop vaccine strategies that can overcome this tolerance and induce immunity potent enough to prevent and treat naturally developing tumors. More recently, we are using a genetic model of pancreatic cancer developed to understand the early inflammatory changes that promote cancer development.

    The identification of human tumor antigens recognized by T cells. We are using a novel functional genetic approach developed in our laboratory. Human tumor specific T cells from vaccinated patients are used to identify immune relevant antigens that are chosen... based on an initial genomic screen of overexpressed gene products. Several candidate targets have been identified and the prevelence of vaccine induced immunity has been assessed .
    This rapid screen to identify relevant antigenic targets will allow us to begin to dissect the mechanisms of tumor immunity induction and downregulation at the molecular level in cancer patients. More recently, we are using proteomics to identify proteins involved in pancreatic cancer development. We recently identified Annexin A2 as a molecule involved in metastases.

    The analysis of antitumor immune responses in patients enrolled on vaccine studies. The focus is on breast and pancreatic cancers. We are atttempting to identify in vitro correlates of in vivo antitumor immunity induced by vaccine strategies developed in the laboratory and currently under study in the clinics.
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    Research Areas: immunology, cancer, anti-cancer drugs

    Lab Website

    Principal Investigator

    Elizabeth Jaffee, M.D.

    Department

    Oncology

  • Eric Nuermberger Lab

    Research in the Eric Nuermberger Lab focuses primarily on experimental chemotherapy for tuberculosis. 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.

    Research Areas: pharmacodynamics, chemotherapy, infectious disease, antimicrobials, drugs, antibiotics, Streptococcus pneumoniae, pneumonia, tuberculosis

    Principal Investigator

    Eric Nuermberger, M.D.

    Department

    Medicine

  • Ernesto Freire Laboratory

    The Ernesto Freire Lab studies the use of novel drugs to treat disease. Our research has resulted in the development of a thermodynamic platform for drug discovery and optimization. Our aim is to achieve high binding affinity and selectivity as well as appropriate pharmacokinetics with the platform. We are currently focusing on drug targets such as HIV/-1 protease inhibitors (HIV/AIDS), plasmepsin inhibitors (malaria), HCV protease inhibitors (hepatitis C), coronavirus 3CL-pro protease inhibitors (SARS and other viral infections), HIV-1 gp120 inhibitors (HIV/AIDS), chymase inhibitors (cardiovascular disease) and beta lactamase inhibitors (antibiotic resistance).

    Research Areas: pharmaceuticals, thermodynamics, AIDS, drug discovery, HIV, protease inhibitors, malaria

  • Frueh Laboratory

    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.

    Research Areas: enzymes, proteomics, imaging, drugs, antibiotics, nuclear magnetic resonance, molecular biology

  • Gabsang Lee Lab

    Human induced pluripotent stem cells (hiPSCs) provide unprecedented opportunities for cell replacement 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 ne...ural 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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    Research Areas: stem cells, human-induced pluripotent stem cells, genomics, drugs, muscular dystrophy, familial dysautonomia

    Principal Investigator

    Gabsang Lee, Ph.D.

    Department

    Neurology

  • Green Group

    The Green Group is the biomaterials and drug delivery laboratory in the Biomedical Engineering Department at the Johns Hopkins University School of Medicine. Our broad research interests are in cellular engineering and in nanobiotechnology. We are particularly interested in biomaterials, controlled drug delivery, stem cells, gene therapy, and immunobioengineering. We are working on the chemistry/biology/engineering interface to answer fundamental scientific questions and create innovative technologies and therapeutics that can directly benefit human health.

    Research Areas: nanobiotechnology, stem cells, biomedical engineering, drugs, immunobioengineering

    Lab Website

    Principal Investigator

    Jordan Green, Ph.D.

    Department

    Biomedical Engineering

  • Gregory Kirk Lab

    Research in the Gregory Kirk Lab examines the natural history of viral infections — particularly HIV and hepatitis viruses — in the U.S. and globally. As part of the ALIVE (AIDS Linked to the Intravenous Experience) study, our research looks at a range of pathogenetic, clinical behavioral issues, with a special focus on non-AIDS-related outcomes of HIV, including cancer and liver and lung diseases. We use imaging and clinical, genetic, epigenetic and proteomic methods to identify and learn more about people at greatest risk for clinically relevant outcomes from HIV, hepatitis B and hepatitis C infections. Our long-term goal is to translate our findings into targeted interventions that help reduce the disease burden of these infections.

    Research Areas: global health, Hepatitis, Africa, AIDS, cancer, HIV, drugs, liver diseases

    Principal Investigator

    Gregory Kirk, M.D., M.P.H., Ph.D.

    Department

    Medicine

  • Herschel Wade Lab

    The emergence of structural genomics, proteomics and the large-scale sequencing of many genomes provides experimental access to regions of protein sequence-structure-function landscapes which have not been explored through traditional biochemical methods. Protein structure-function relationships can now be examined rigorously through the characterization of protein ensembles, which display structurally convergent--divergent solutions to analogous or very similar functional properties.

    In this modern biochemical context, the Herschel Wade Lab will use protein libraries, chemistry, biophysics, molecular biology and structural methods to examine the basis of molecular recognition in the context of several important biological problems, including structural and mechanistic aspects of multi-drug resistance, ligand-dependent molecular switches and metal ion homeostasis.

    Research Areas: biophysics, biochemistry, proteomics, genomics, drugs, molecular biology

  • James Barrow Laboratory

    The James Barrow Laboratory studies drug discovery at the Lieber Institute. He leads research related to medicinal chemistry, biology, and drug metabolism, with the goal of validating novel mechanisms and advancing treatments for disorders of brain development.

    Research Areas: brain development, drugs, chemistry, biology

  • Jay Baraban Laboratory

    The Jay Baraban Laboratory studies key aspects of neuronal plasticity induced by environmental stimuli, including drugs. The ability of the microRNA system to regulate protein translation in the vicinity of synapses indicates it is well positioned to play a central role in regulating synaptic plasticity. Accordingly, we are studying how this system regulates synaptic function. In particular, we have identified the translin/trax RNAse complex as a key regulator of microRNA processing and are using genetically engineered mice that lack this complex to understand its role in neuronal function. For example, these mice display defects in responsiveness to cocaine and in certain forms of synaptic plasticity. We use a combination of behavioral and molecular approaches to conduct studies aimed at understanding how the microRNA system regulates these processes.

    Research Areas: synaptic plasticity, neuronal plasticity, drugs, RNA

    Principal Investigator

    Jay Baraban, M.D., Ph.D.

    Department

    Neuroscience

  • Jodi Segal Lab

    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.

    Research Areas: blood disorders, osteoporosis, diabetes, drugs, evidence-based medicine

    Principal Investigator

    Jodi Segal, M.D., M.P.H.

    Department

    Medicine

  • John Schroeder Lab

    The John Schroeder Lab focuses on understanding the role human basophils and mast cells play in allergic reactions, as it relates not only to their secretion of potent inflammatory mediators (e.g., histamine and leukotriene C4) but also to their production of pro-inflammatory cytokines. We have long utilized human cells rather than cell lines in order to address the parameters, signal transduction and pharmacological aspects underlying clinically relevant basophil and mast cell responses. As a result, the lab has established protocols for rapidly isolating large numbers of basophils at high purity from human blood and for growing culture-derived mast cells/basophils from human progenitor cells. A variety of assays and techniques are also in place for concurrently detecting cytokines and mediators following a wide range of stimuli. These have facilitated the in vitro testing of numerous anti-allergic drugs for inhibitory activity on basophil and mast cell activation. The lab also studie...s counter-regulation between the IgE and innate immune receptors on human immature dendritic cell subtypes. view more

    Research Areas: cell biology, allergies, inflammation

    Principal Investigator

    John Schroeder, Ph.D.

    Department

    Medicine

  • John T. Isaacs Laboratory

    While there has been an explosion of knowledge about human carcinogenesis over the last 2 decades, unfortunately, this has not translated into the development of effective therapies for either preventing or treating the common human cancers. The goal of the Isaacs’ lab is to change this situation by translating theory into therapy for solid malignancies, particularly Prostate cancer. Presently, a series of drugs discovered in the Isaacs’ lab are undergoing clinical trials in patients with metastatic cancer.

    The ongoing drug discovery in the lab continues to focus upon developing agents to eliminate the cancer initiating stem cells within metastatic sites of cancer. To do this, a variety of bacterial and natural product toxins are being chemically modified to produce “prodrugs” whose cytotoxicity is selectively activated by proteases produced in high levels only by cancer cells or tumor associated blood vessel cells. In this way, these prodrugs can be given systemically to metastati...c patients without un-acceptable toxicity to the host while being selectively activated to potent killing molecules within metastatic sites of cancer.

    Such a “Trojan Horse” approach is also being developed using allogeneic bone marrow derived Mesenchymal Stem cells which are genetically engineered to secrete “prodrugs” so that when they are infused into the patient, they selectively “home” to sites of cancers where the appropriate enzymatic activity is present to liberate the killing toxin sterilizing the cancer “neighborhood”.
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    Research Areas: anti-cancer drugs, stem cell biology

    Lab Website

    Principal Investigator

    John Isaacs, Ph.D.

    Department

    Oncology

  • Jun O. Liu Laboratory

    The Jun O. Liu Laboratory tests small molecules to see if they react in our bodies to find potential drugs to treat disease. We employ high-throughput screening to identify modulators of various cellular processes and pathways that have been implicated in human diseases from cancer to autoimmune diseases. Once biologically active inhibitors are identified, they will serve both as probes of the biological processes of interest and as leads for the development of new drugs for treating human diseases. Among the biological processes of interest are cancer cell growth and apoptosis, angiogenesis, calcium-dependent signaling pathways, eukaryotic transcription and translation.

    Research Areas: cancer, autoimmune, eukaryotic cells, drugs, cellular signaling, pharmacology, calcium-dependent signaling pathways, molecular biology, angiogenesis

  • Karakousis Lab

    The Karakousis Lab is primarily focused on understanding the molecular basis of Mycobacterium tuberculosis persistence and antibiotic tolerance. A systems biology-based approach, including the use of several novel in vitro and animal models, in combination with transcriptional, proteomic, genetic, imaging, and computational techniques, is being used to identify host cytokine networks responsible for immunological control of M. tuberculosis growth, as well as M. tuberculosis regulatory and metabolic pathways required for bacillary growth restriction and reactivation. In particular, we are actively investigating the regulatory cascade involved in the mycobacterial stringent response. Another major focus of the lab is the development of host-directed therapies for TB, with the goal of shortening treatment and improving long-term lung function. Additional research interests include the development of novel molecular assays for the rapid diagnosis of latent TB infection and active TB diseas...e, and for the detection of drug resistance. view more

    Research Areas: diagnostics, persistence, infectious disease, Mycobacterium tuberculosis, host-directed therapy, latency, drugs, antibiotics, tuberculosis

    Lab Website

    Principal Investigator

    Petros Karakousis, M.D.

    Department

    Medicine

  • Kelly E. Dooley Laboratory

    Research focuses on clinical pharmacology of new anti-tuberculosis regimens with an emphasis on: (1) Phase I clinical trials of new or existing anti-TB drugs including dose escalation trials and studies of drug-drug interactions between anti-TB agents and antiretrovirals to treat HIV; (2) Use of PK/PD analysis and modelling in Phase II tuberculosis clinical treatment trials to determine concentration-effect relationships that will allow for optimization of dosing; and (3) Evaluation of TB and HIV drug concentrations in special populations, such as pregnant women and children; (4) Evaluation of treatment-shortening regimens for drug-sensitive TB and investigational regimens for treatment of multidrug-resistant TB; and (5) Translational work involving novel animal models of cavitary pulmonary TB disease to understand drug distribution in diseased lung.

    Research Areas: anti-infective drugs, antiretroviral therapies, tuberculosis and HIV treatments, HIV, lung disease, pharmacology, tuberculosis

    Lab Website

    Principal Investigator

    Kelly Dooley, M.D., M.P.H., Ph.D.

    Department

    Medicine

  • Le Cancer Metabolism Research Lab

    Dr. Anne Le's research primarily focuses on cancer metabolism and metabolic aspects of other diseases. Using metabolomics technologies, her work has led to breakthrough discoveries revealing several characteristic features of the metabolism of cancer. One of these, the dependence of cancer cells on glutamine metabolism, has translated into clinical trials as a novel therapy for cancer patients. Furthermore, her lab tracked the metabolic pathways in the remaining tumor cells after this novel therapy and identified the best-suited drugs for combined synergistic therapy. The depth of Dr. Le's expertise in cancer metabolism, in collaboration with other experts at Johns Hopkins, will lead to improved outcomes for cancer therapy.

    Research Areas: cancer, metabolomics technologies, cancer metabolism

  • Mark Donowitz Lab

    Research in the Mark Donowitz Lab is primarily focused on the development of drug therapy for diarrheal disorders, intestinal salt absorption and the proteins involved including their regulation, and the use of human enteroids to understand intestinal physiology and pathophysiology. We study two gene families initially recognized by this laboratory: mammalian Na/H exchangers and the subgroup of PDZ domain containing proteins present in the brush border of epithelial cells called NHERF family. A major finding is that NHE3 exists simultaneously in different sized complexes in the brush border, which change separately as part of signal transduction initiated by mimics of the digestive process. Relevance to the human intestine is being pursued using mini-human intestine made from Lgr5+ stems cells made from intestinal biopsies and measuring function via two-photon microscopy.

    Research Areas: gastrointestinal system, gastroenterology, pathophysiology, diarrhea, drugs, physiology

    Lab Website

    Principal Investigator

    Mark Donowitz, M.D.

    Department

    Medicine

  • Michael Kornberg Lab

    Our laboratory conducts basic and translational research aimed at better understanding the pathogenesis of multiple sclerosis (MS) and the role of the immune system in CNS disease, particularly the processes that drive progressive disability such as neurodegeneration and remyelination failure. We currently have three parallel research programs: 1. Metabolism as a modulator of MS: We are studying how basic metabolic pathways regulate the immune system and how these pathways might be exploited to protect neurons and myelin-forming oligodendrocytes from injury. 2. Identifying pathways by which nitric oxide (NO) and other free radicals cause neuronal and axonal damage. Our lab is identifying specific signaling pathways initiated by NO and other free radicals that can be targeted by drugs to produce neuroprotection. 3. Modulating the innate immune system in MS: In collaboration with others at Johns Hopkins, we are studying ways to enhance the reparative functions of microglia while preventi...ng maladaptive responses. This work has identified bryostatin-1 as a potential drug that may be re-purposed for this task. view more

    Research Areas: multiple sclerosis

  • Namandje N. Bumpus Lab

    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.

    Research Areas: antiviral therapy, drug metabolism, mass spectrometry, HIV, drugs, cellular signaling, cytochromes P450, pharmacology, molecular pharmacology, hepatitis C, metabolomics

    Lab Website

    Principal Investigator

    Namandje Bumpus, Ph.D.

    Department

    Medicine

  • Richard Rivers Lab

    The Richard Rivers Lab researches vascular communication with a focus on microcirculation physiology. Our team seeks to determine how metabolic demands are passed between tissue and the vascular network as well as along the vascular network itself. Our goal is to better understand processes of diseases such as cancer and diabetes, which could lead to the development of more targeted drugs and treatment. We are also working to determine the role for inwardly rectifying potassium channels (Kir) 2.1 and 6.1 in signaling along the vessel wall as well as the role of gap junctions.

    Research Areas: cancer, potassium, diabetes, vascular biology, vascular, microcirculation

  • Robert Siliciano Laboratory

    Research in the Robert Siliciano Laboratory focuses on HIV and antiretroviral therapy (ART). ART consists of combinations of three drugs that inhibit specific steps in the virus life cycle. Though linked to reduced morbidity and mortality rates, ART is not curative. Through our research related to latently infected cells, we've shown that eradicating HIV-1 infection with ART alone is impossible due to the latent reservoir for HIV-1 in resting CD4+ T cells.

    Our laboratory characterized the different forms of HIV-1 that persist in patients on ART. Currently, we are searching for and evaluating drugs that target the latent reservoir. We are also developing assays that can be used to monitor the elimination of this reservoir. We are also interested in the basic pharmacodynamic principles that explain how antiretroviral drugs work. We have recently discovered why certain classes of antiretroviral drugs are so effective at inhibiting viral replication. We are using this discovery along w...ith experimental and computational approaches to develop improved therapies for HIV-1 infection and to understand and prevent drug resistance. Finally, we are studying the immunology of HIV-1 infection, and in particular, the ability of some patients to control the infection without ART. view more

    Research Areas: antiretroviral therapies, HIV, drugs, pharmacology, drug resistance, T cells

    Principal Investigator

    Robert Siliciano, M.D., Ph.D.

    Department

    Medicine

  • Sandra Gabelli Lab

    The Gabelli lab research is focused on structural, mechanistic and functional aspects of enzyme activation that play a role in the biology of human diseases such as cancer, parasitic infection and cardiovascular disease. Their work seeks to:

    1. Understand how molecular events at the recognition level coordinate and trigger events in the cells
    2. Translate structural and mechanistic information on protein:protein interactions at the cytoplasmic level into preventive and therapeutic treatment for human disease.

    To achieve a comprehensive understanding, they are studying cytoplasmic protein-protein interactions involved in regulation of pathways such as PI3K and Sodium Voltage gated channels. Their research integrates structural biology and chemical biology and it is focused on drug discovery for targeted therapies.

    Research Areas: biochemistry, chemical biology, cell biology, structural biology, proteomics, cancer, diarrhea, diabetes, drugs, cellular signaling, inflammation, pharmacology

    Lab Website

    Principal Investigator

    Sandra Gabelli, Ph.D.

    Department

    Medicine

  • Solomon Snyder Laboratory

    Information processing in the brain reflects communication among neurons via neurotransmitters. The Solomon Snyder Laboratory studies diverse signaling systems including those of neurotransmitters and second messengers as well as the actions of drugs upon these processes. We are interested in atypical neurotransmitters such as nitric oxide (NO), carbon monoxide (CO), and the D-isomers of certain amino acids, specifically D-serine and D-aspartate. Our discoveries are leading to a better understanding of how certain drugs for Parkinson's disease and Hungtington's disease interact with cells and proteins. Understanding how other second messengers work is giving us insight into anti-cancer therapies.

    Research Areas: Huntington's disease, amino acids, neurotransmitters, brain, cancer, nitric oxide, drugs, carbon monoxide, Parkinson's disease, nervous system

  • The Hillel Lab

    The Hillel Laboratory at Johns Hopkins investigates inflammatory, genetic, and molecular factors involved with laryngotracheal stenosis, or scar formation in the airway. Specifically, we are examining the interrelationship between genetics, the immune system, bacteria, and scar formation in the airway. The lab has developed unique models to study laryngotracheal stenosis and test drugs that may halt the progression of scar or reverse scar formation. We are also developing a drug-eluting stent to treat patients with laryngotracheal stenosis.

    Research Areas: complex airway disorders, laryngotracheal stenosis

  • Theresa Shapiro Laboratory

    The Theresa Shapiro Laboratory studies antiparasitic chemotherapy. On a molecular basis, we are interested in understanding the mechanism of action for existing antiparasitic agents, and in identifying vulnerable metabolic targets for much-needed, new, antiparasitic chemotherapy. Clinically, our studies are directed toward an evaluation, in humans, of the efficacy, pharmacokinetics, metabolism and safety of experimental antiparasitic drugs.

    Research Areas: sleeping sickness, infectious disease, drugs, malaria, pharmacology, antiparasitic chemotherapy, molecular biology

    Principal Investigator

    Theresa Shapiro, M.D., Ph.D.

    Department

    Medicine

  • William Bishai Laboratory

    The William Bishai Laboratory studies the molecular pathogenesis of tuberculosis. The overall goal of our laboratory is to better understand tuberculosis pathogenesis and then to employ this understanding toward improved drugs, vaccines and diagnostics. Since Mycobacterium tuberculosis senses and adapts to a wide array of conditions during the disease process, it is clear that the regulation of expression of virulence factors plays an important role in pathogenesis. As a result, a theme of our research is to assess mycobacterial genes important in gene regulation. We are also interested in cell division in mycobacteria and the pathogenesis of caseation and cavitation.

    Research Areas: vaccines, genomics, drugs, pathogenesis, tuberculosis

    Lab Website

    Principal Investigator

    William Bishai, M.D., Ph.D.

    Department

    Medicine

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