Research Topics: Basic Tumor Biology, Signal Transduction
Control of Cell Growth, Differentiation and Survival by Ras- and Rho-related Proteins.
Ras- and Rho-related proteins are small GTPases activated downstream of multiple receptors that control many cellular processes including cell cycle progression, apoptosis, cell motility, and cellular differentiation. Since they promote transformation and tumor metastasis, they represent important targets for cancer therapy. We have investigated the effects of prenylation inhibitors (agents that inhibit important post-translational modifications of Ras and Rho) on signaling in solid tumors and leukemic cells. Through a proteomics approach, we have identified novel Rho effector proteins, and defined their functions in cancer cells. We are also interested in the cross-talk between Ras and Rho and other signaling pathways, and are examining mechanisms whereby cAMP- and cGMP-dependent protein kinases regulate the activities of these proteins.
Regulation of Gene Expression by NO/cGMP/cGMP-dependent Protein Kinases.
We have identified a number of genes and transcription factors regulated by nitric oxide (NO) and cGMP through activation of cGMP-dependent protein kinases (PKGs), and have characterized different mechanisms of transcriptional regulation by PKGs. We are studying the role of PKG isoforms in the regulation of genes important for growth and differentiation of primary vascular smooth muscle cells, osteoblasts, and mesenchymal stem cells. We found that type II PKG plays a crucial role in osteoblast mechano-transduction and estrogen signaling, and have defined mechanisms whereby PKG II activates Src, Erk and Akt in cells. We found that type I PKG promotes cell survival and motility in several systems, and are investigating mechanisms whereby NO/cGMP signaling can affect breast cancer invasiveness. We have identi¬fied isoform-specific PKG anchoring proteins and are determining how they restrict and define cGMP signaling within cells.
Education and Training
Baccalaureate Mathematics/Physics - Kranich Gymnasium,Salzgitter, Germany - 1974
MD - Medical School of Hannover, Hannover, Germany - 1981
Research Fellow - University of California, San Diego - 1981-1983
Intern - University of California, San Diego - 1983-1984
Resident - University of Cologne, Germany - 1984-1985
Resident - University of California, San Diego - 1985-1987
Fellow Hematology/Oncology - University of California, San Diego - 1987-1990