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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).
Biophysics and Biophysical Chemistry
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.
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.
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.
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.
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.
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.
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.
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
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”. view less