shuman@medicine.ucsf.edu
(415) 476-2120 (lab); (415) 514-4661 (fax)

Box 1270, UCSF; San Francisco, CA 94143-1270

deliveries: 513 Parnassus Avenue, HSE-1217; San Francisco, CA

Full Biosketch

Dora Ayala-Payne; Sebastian Bernales, PhD; Juliana Karrim, MD; Cigall Kadoch

Our lab is focused on understanding the genetic and biochemical mechanisms underlying tumor progression: growth, invasion, and metastasis. Laboratory members are working on complex problems in prostate, breast, and brain tumors, including identifying proteases expressed by these tumors, determining their role in tumor progression, and characterizing proteases essential for tumor-induced angiogenesis. Finally, the lab is working on translating these findings into new approaches to cancer prevention and treatment by developing new classes of protease inhibitors.

The Shuman Lab is collaborating with the laboratory of Charles Craik, PhD on studies of a new transmembrane serine protease that they have discovered, MT-SP1 (membrane type- serine protease-1). MT-SP1 is expressed in gastrointestinal and genitourinary cancers, and preliminary evidence suggests that its expression is associated with shortened survival.

Ongoing research in this area includes: creation of of a transgenic mouse in which the MT-SP1 gene is deleted by homologous recombination; and characterizing the effect of a recombinant serine protease inhibitor, ecotin, with a nm Ki against chymotypsin-class proteases on the effect of tumor progression in a transgenic model of prostate cancer (TRAMP).

In another collaboration, the lab is interested in the three-dimensional structure of the urokinase (uPA) - uPA receptor (uPAR). The lab has produced recombinant forms of each protein, from which the lab of the late Cara Marks, PhD, was able to obtain crystals suitable for x-ray diffraction analysis. The laboratory of Robert Fletterick, PhD, is carrying out these studies. Structural information will be used to design potent inhibitors of the ligand receptor interaction. Evidence previously obtained by the Shuman Lab suggests that inhibition of uPAR leads to inhibition of tumor growth and metastasis.

The Shuman Lab also plans to backcross transgenic mice in which genes for specific metalloproteases have been knocked out with TRAMP mice to determine the role of these proteases on tumor progression. Previous research by the lab suggests that a transmembrane metalloprotease, MT-MMP1, is involved in prostate cancer progression.