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- LMP Website
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- Positions
- Laboratory Chief
- Yves Pommier
- Investigators
- Mirit I Aladjem
- William M. Bonner
- James H. Doroshow
- Kurt W. Kohn
- Vladimir L. Larionov
- Patricia S. Steeg
- Staff Scientists
- Smitha Antony
- Natalay Y. Kouprina
- Christophe Marchand
- Diane Palmieri
- Christophe E. Redon
- Olga Sedelnikova
- Barry Zeeberg
- Hongliang Zhang
Our Science – LMP Website
Laboratory of Molecular Pharmacology
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| In addition to the information presented below, the LMP has an alternative website that can provide you with more detail about their work. |
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Research
The main focus of the Laboratory of Molecular Pharmacology (LMP) is to explore possible connections between molecular biology alterations that drive malignant cell proliferation and potential avenues for therapy. To achieve this, LMP investigators (1) dissect the molecular interactions between effective anticancer drugs and their molecular targets; (2) identify novel genes and pathways that determine the occurrence of breast and prostate cancers and their metastatic progression; (3) focus in molecular detail on chromatin, its abilities to repair DNA damage, and its responses to chemotherapeutic agents with particular emphasis on DNA topoisomerases, nucleosome roles in chromatin function, initiation of DNA replication, centromere and kinetochore structure; (4) investigate the emerging importance of oxidant-mediated signaling in tumor growth and therapeutic response; and (5) integrate the growing knowledge of the molecular regulatory networks of neoplastic cells to discover new drugs or therapeutic strategies and molecular markers that predict the response of individual tumors to particular drug therapies. The laboratory is organized into several research groups, each focusing on specific areas of interest:
- The study of topoisomerases, DNA repair and cell cycle checkpoints as targets of anticancer drugs (Yves Pommier) probes the mechanisms of action of drugs at the molecular level and compares new compounds to those that are presently used in cancer chemotherapy. Novel agents that target DNA or its activities such as replication, recombination, and repair are investigated. Human cancer cell lines are being characterized to determine the factors and genes that govern drug susceptibility.
- Investigations of genome integrity (William Bonner) include both basic and translational studies concerning DNA double-strand damage and its role in cancer formation, cancer treatment, aging, and degenerative diseases. Current research includes structural and functional studies on the phosphorylation of H2AX to form foci at sites of DNA double strand damage, translational studies on medical biodosimetric uses of H2AX phosphorylation, and studies of communication among cells during damage and disease processes.
- Analyses of DNA replication (Mirit Aladjem) focus on the molecular processes that deliver information from cell cycle regulators to the DNA duplex. These studies combine biochemical analysis with recombinase-mediated gene targeting to identify DNA sequences that are essential for initiation of DNA replication and probe into cellular regulators that interact with these sequences.
- Studies the structure of cancer-related genes (Vladimir Larionov) to understand why particular chromosomal regions are prone to generate genomic disorders including gene duplication and the structure of centromeres whose function underlies proper chromosome segregation, which, when aberrant, leads to aneuploidy and polyploidy, which are hallmarks of many cancers. Construction of human artificial chromosomes (HACs) is actively pursued to study centromere structure and functions and to develop novel gene therapy vectors and to study organization and function of the human kinetochore.
- Basic and translational research on the molecular biology and pharmacology of breast cancer (Patricia Steeg) with four major projects under investigation: (1) What is the role of the nm23 metastasis suppressor gene in breast cancer progression? (2) What molecular events are involved in breast cancer metastasis to the brain? (3) Develop model systems for the treatment of such breast cancer metastasis to the brain? (4) What molecular events are responsible for early neoplastic progression in the breast?
- Elucidate the role of oxidant-mediated signaling (James Doroshow) in growth factor- and drug-related inhibition of tumor cell proliferation with particular interest in the epithelial NADPH oxidase gene family and the development of novel small molecular inhibitors of these proteins.
- Studies of the integrated behavior of cell regulatory networks (Kurt Kohn) elucidate the relationship of the cellular networks/pathways and the cellular responses to chemotherapeutic agents and propose novel therapeutic strategies for cancer treatment and innovative drug associations.
- HIV integrase as a target of antiviral drugs (Yves Pommier) involves a search for novel inhibitors of this essential enzyme for retroviral replication, and determines the molecular interactions between inhibitors and HIV-1 integrase.
- The Genomic and Bioinformatics Group (managed by William Reinhold) explores relationships between the genetic makeup of malignant cells and their response to chemotherapeutic agents using multiple molecular databases at the DNA, RNA, protein levels, and drug responses for the 60 cell lines of the NCI Anticancer Drug Screen. Web-based electronic Molecular interaction maps (eMIMs) (Kurt Kohn, Mirit Aladjem, Yves Pommier) are also developed in the group (http://discover.nci.nih.gov/mim).
This page was last updated on 2/24/2009.
