 |
 |
 |
|
|
|
|
|
|
|
|
|
| UCSF-MDI
Proteases in Cancer Program Project Grant
UCSF TEAM TO RECEIVE $7.4M TO EXPLORE WAYS TO FIGHT CANCER BY TARGETING TUMOR ENZYMES
Program Overview
"Mechanisms
of Tumor Growth and Invasion Mediated by Proteolysis"
UCSF-MDI Proteases in
Cancer Program Project Grant
This Program Project coordinates a multidisciplinary
effort to evaluate the biological significance and therapeutic potential
of certain proteases associated with epithelial cancers. More specifically,
tumor specimens obtained from patients and pre-clinical tumor models will
be screened to identify prominent associated proteases. These, in turn,
will be studied in novel systems to determine their precise role in tumor
pathogenesis and progression as well as in neovascularization. Molecular
modeling, structure based library screening, synthetic chemistry and protein
engineering will be utilized to identify small molecule and macromolecular
inhibitors or proteases that will be used to further evaluate protease
function and to examine protease effects on tumor growth and development.
Selective inhibitors and the use of novel transgenic and knockout animal
systems should provide useful information on the role of proteases in various
stages of tumor development and progression. Information of this type will
undoubtedly contribute to our understanding of tumor biology and, ultimately,
to our ability to develop more effective and tumor-selective anticancer
strategies.
PROJECT 1
PROJECT 2
PROJECT 3
CORE A
CORE B
J. H. McKerrow, PhD,MD, Professor, Departments of Pathology, Medicine and Pharmaceutical Chemistry; Director, Tropical Disease Research Unit; Director, Laboratory of Molecular Pathology CORE C
CORE D
The Molecular Design Institute (MDI) serves as the administrative focus for the UCSF PPG application. The MDI is an Organized Research Unit (ORU) of the University of California, San Francisco. The goal of the Molecular Design Institute is to promote and coordinate research and education in the broad area of molecular design with particular emphasis on drug design. Specifically, the MDI focuses on the development of new methods to aid in the discovery of novel pharmaceutical agents. A major focus is to bridge the existing academic disciplines and departments to enhance progress in all aspects of this important area. The specific aims of the MDI are: Structure based molecular design applies the principles of chemistry, medicinal chemistry, biochemistry and molecular biology to the design and development of bioactive agents such as drugs. Ideas from mathematics and computer science are also incorporated. The result is a comprehensive approach that can be of great practical importance. New approaches to molecular design have attracted wide-spread attention throughout the academic community and the chemical and pharmaceutical industry. The new initiatives come from the perception that conventional approaches (e.g., screening of natural products) have reached the point of diminishing returns in developing new pharmaceutical agents. An equal driving force has been the major scientific advances that have flowered in the past decade in areas such as protein crystallography, magnetic resonance, pharmacokinetics and molecular biology. There have been orders of magnitude improvement in computational simulations and computer graphics. Taken together, the tools are in place for very significant advances. UCSF has an outstanding reputation because of its strengths in medicinal and computational chemistry, biochemistry, molecular biology and academic and clinical medicine. UCSF has a paramount position, nationally and internationally, in many of these activities, but the expertise is spread amongst several departments in three different schools. Traditional departmental structures do not adapt readily to new technological advances. It would greatly strengthen this diverse community to have a core entity to provide central facilities and to focus activities. The Molecular Design Institute provides an intellectual and scientific clearinghouse for faculty members from several departments. It will develop facilities that would drive effective fundamental research in the structural sciences and provide for the hands-on training of students, fellows, and visiting scientists. Because molecular design projects are truly interdisciplinary, the MDI can be expected to encourage and extend the current strong position of UCSF. An important role of the Molecular Design Institute is to promote interactions with the pharmaceutical industry. By providing a mechanism for frequent exchange of views and plans and by bringing together a group of faculty members with experience in interacting with the private sector, it can help coordinate faculty and administration activities for long-term industry/campus relationships. The Molecular Design Institute encourages research in molecular structure, structural biology, medicinal chemistry, molecular calculations, computer graphics, biopharmaceutics, enzymology, toxicology, biotechnology and molecular medicine. The principles of physical and organic chemistry will be applied to questions of macromolecular interactions and the design of drugs. Some research areas of most interest are:
|
