Molecular Therapeutics

The goal of the Molecular Therapeutics Program is to integrate basic and translational science to develop novel therapeutic agents and clinical trials that have strong scientific rationales.

The program is comprised of investigators whose work relates to five major categories:

• drug discovery/structural biology
• drug delivery
• G protein signal transduction pathways relevant to oncogenesis and treatment
• integrin signaling, adhesion, and metastasis, and
• mechanisms of drug action and clinical trials.

Research by program members has resulted in a number of exciting findings, among which are the elucidation of the structure of Topoisomerase I /DNA complex, advances in the use of antisense and cell targeting technologies, development of antisense approaches to manipulate the pre-mRNA splicing of pro- and antiapoptotic molecules, elucidation of mediators of oncogenesis by small G protein family members, discovery of a new class of proteins that couples G protein receptor signaling to mitotic separation of chromosomes, development of a nucleoside analog for leukemia treatment, and the application of proteasome inhibition to the treatment of multiple myeloma.

The program adds value to the center by bringing chemists, cell biologists, pharmacologists, and clinical and translational researchers together to participate in new drug discovery, the elucidation of mechanisms of action of therapeutically relevant compounds, and innovative clinical trials. The 29 Program members come from six Schools of Medicine, Pharmacy, and College of Arts and Sciences departments.

Members are major participants in two program project grants. Direct cost funding in 2003 was $12.9 million including $3.2 million in NCI research funding and $3.4 million in all NCI funding. Members generated 444 publications over the past four years, of which ~13 % were intraprogrammatic collaborations.

Dr. Gary Johnson, the program leader, is the recently recruited Chair of Pharmacology and is renowned for his research defining MAPK signal transduction pathways and their biologic significance. The leadership is united in its goals for program development. Molecular Therapeutics is poised to expand its drug discovery component with new recruitment of chemists, to develop rationale approaches to high-throughput drug screening in live cells, to further its relationships with the Pharmaceutical Industry, and to develop new, innovative Phase I clinical trials.