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.