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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.
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 less
Our scientists pursue out-of-the-box approaches at the very edge of knowledge to:
1) Elucidate the molecular/cellular/physiological landscapes of ovarian and uterine cancers.
2) Understand the earliest events in their development and mechanisms of tumor evolution/dormancy and drug resistance.
3) Deliver promises for better prevention, detection and treatment to women who have diseases or are at an increased risk to have these cancers.
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 less
Chronic viral hepatitis (due to HBV and HCV) is a major cause of liver disease worldwide, and an increasing cause of death in persons living with HIV/AIDS. Our laboratory studies are aimed at better defining the host-pathogen interactions in these infections, with particular focus on humoral and cellular immune responses, viral evasion, inflammation, fibrosis progression, and drug resistance. We are engaged in synthetic biology approaches to rational vaccine development and understanding the limits on the extraordinary genetic variability of HCV.
The Cohen Lab
Combining microbiology and bioinformatics, the Cohen Lab conducts translational research on mycobacteria. By application of advanced genomic techniques to the problems of tuberculosis and nontuberculous mycobacteria, the Cohen Lab aims to develop improved tools for the diagnosis and management of mycobacterial disease.