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Thomas Hermann
RNA as a Drug Target |
| Contact Information |
| Office: PACH 5222A |
| Phone: (858) 534-4467 |
| Fax: (858) 534-0202 |
| Email: tch@ucsd.edu |
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| Education and Appointments |
| 2001-2005 |
Head of, Structural Chemistry Department, Anadys Pharmaceuticals, San Diego
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| 1999-2000 |
Postdoc, Memorial Sloan-Kettering Cancer Center, New York
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| 1996-1998 |
Postdoc, Institut de Biologie Moleculaire et Cellulaire, CNRS, Strasbourg, France
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| 1996 |
Ph.D., Max-Planck-Institute for Biochemistry and Ludwig-Maximilians-University Munich, Germany
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| 1992 |
Diploma, University of Ulm, Germany
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| Awards and Academic Honors |
| 1996-1998 |
EMBO Long-Term Fellow |
| 1996 |
Otto-Hahn Medal of the Max-Planck Society, Germany |
| Research Interests |
We are exploring the molecular recognition of ribonucleic acid (RNA) by small molecules.
RNA molecules participate as key players in many biological processes and adopt complex architectures that are required for function. The development of ligands that bind specifically to RNA targets opens exciting new ways to expand greatly the existing repertoire of protein-directed therapeutics. We focus on four areas of research and apply diverse techniques, including molecular biology, biochemistry, X-ray crystallography, computational chemistry as well as synthetic organic chemistry:
Validation and Screening of New RNA Targets
We use molecular biological and biochemical methods to explore new RNA targets in two therapeutic areas: hepatitis C virus infection (HCV) and cancer. Screening assays are being developed that report on functional consequences of ligand binding to an RNA target in addition to returning binding affinity.
Structure Determination of RNA Targets and Ligand Complexes
We use X-ray crystallography to investigate the three-dimensional architecture of RNA targets and their complexes with small molecules of both natural and synthetic origin.
Computational Chemistry of RNA-Ligand Interaction
Structural information from crystallography, along with data from biochemical experiments are combined to investigate in silico the molecular recognition of RNA. We want to develop rules that define RNA-friendly ligands, which will ultimately be applied to the design of novel synthetic ligands.
Design and Synthesis of New Ligands for RNA Targets
Structure-guided design is combined with ligand-based approaches to develop focused small molecule libraries for screening against RNA targets. We develop syntheses for new RNA-friendly molecules of natural product-like complexity.
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Interdisciplinary Specialties: |
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Organic Chemistry
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Bioorganic
Macromolecular Structure
Computational and Theoretical
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| Selected Publications |
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Hermann T,
"Drugs targeting the ribosome." Curr Opin Struct Biol 3(355-66):
, 2005. [Go to PubMed]
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Dibrov SM,
Johnston-Cox H,
Weng YH,
Hermann T,
"Functional architecture of HCV IRES domain II stabilized by divalent metal ions in the crystal and in solution." Angew Chem Int Ed Engl 1-2(226-9):
, 2007. [Go to PubMed]
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Parsons J,
Castaldi MP,
Dutta S,
Dibrov SM,
Wyles DL,
Hermann T,
"Conformational inhibition of the hepatitis C virus internal ribosome entry site RNA." Nat Chem Biol 11(823-5):
, 2009. [Go to PubMed]
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