Molecular & Structural Biology

Program Leader: David J. Weber, Ph.D.
Clinical Leader: Ronald Gartenhaus, M.D.

See the complete list of Molecular and Structural Biology investigators.

The Molecular and Structural Biology Program (MSB) is composed of members from many Departments in the Schools of Medicine and Pharmacy at UMB and UMCP. Although varied, the research interests of the group can be divided into three broad areas, including:

  • DNA damage and repair
  • Genome instability
  • Structural biology

Because of this, the Program has initiated a strong effort to develop a focus that will allow the identification of candidate proteins that may serve as markers for malignancy and/or targets for new drug development.

Through the use of cDNA array, genomics, and proteomics technology, proteins and genes of interest are identified and characterized. Solution and/or crystal structures of relevant polypeptides and proteins are determined and once solved, used as substrates for computer assisted drug design and screening (CADDS) to identify small molecule site-specific inhibitors and/or activators. These lead compounds are to be tested in preclinical studies and, where appropriate, developed for Phase 1 clinical trials carried out in the University of Maryland Greenebaum Cancer Center. This is a highly effective approach to new drug discovery, and has already been used successfully to identify several lead compounds that disrupt the binding of p53 with S100B, resulting in the reactivation of wild type p53 function.

The compounds were discovered first by solving the solution structure of the interface between these two proteins and then, based upon CADDS results and database screening, identifying small molecules potentially capable of disrupting that interface. The Program has also supported the Center’s initiative to develop a proteomics shared service for protein identification and, for structural determinations, has encouraged its members to utilize the School of Medicine NMR Center, which is directed by a member of the MSB Program and partially supported by the Cancer Center and houses 500 and 600 MHz machines and will contain a recently contracted 800 MHz machine as well.

The Program is also assisting the Cancer Center with its collaborative effort with the School of Pharmacy to recruit and equip a crystallographer and to establish a University-wide X-ray crystallography center. The Program strongly supports the development of intra- and inter-programmatic collaborations and the formation of translational research initiatives. The MSB Program meets monthly to discuss ongoing projects and Cancer Center affairs. Program members utilize all of the shared services offered by the Center.

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