Faculty Profile
Dr. Pilz
Renate Pilz, M.D.
Professor of Medicine
Office Address:
Division of Hematology-Oncology
University of California
9500 Gillman Drive, MC-0652
La Jolla, CA 92093
rpilz@ucsd.edu
Office: (858) 534-8805
FAX: (858) 534-1421
Education and Training
| Baccalaureate | Mathematics/Physics, Kranich Gymnasium,Salzgitter, Germany | 1974 |
| MD | Medical School of Hannover, Hannover, Germany | 1981 |
| Intern | University of California, San Diego | 1983-1984 |
| Resident | University of California, San Diego | 1985-1987 |
| Fellow | Hematology/Oncology, University of California, San Diego | 1987-1988 |
Research Interests
Dr. Pilz is working on two projects.
1. 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 lprogression, apoptosis, gene expression and cellular differentiation. Since they promost 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 modification of Ras and Rho) on signaling in solid tumors and leukemic cells. Through a proteomics approach, she has identified several novel Rho effector proteins, and are currently defining their functions in cancer cells. She is 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.
2. Regulation of Gene Expression by NO/cGMP/cGMP-Dependent Protein Kinases. Dr. Pilz has identified a number of genes and transcription factors regulated by nitric oxide (NO) and cGMP through activation of cGMP-dependent protein kinases (PKGs), and are pursuing different mechanisms of t ranscriptional regulation by PKGs. She and her colleagues 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 leukemia cells. They found that type II PKG plays a crucial role In osteoblast mechano-transduction and survival, and are presently defining mechanisms whereby PKG II activates Erk and Akt in these cells. We have identified isoform-specific PGK anchoring proteins and are determining how they restrict and define cGMP signaling within cells.
Publications
Chen JC, Zhuang S, Nguyen TN, Boss GR, Pilz RF. Oncogenic Ras leads to Rho activation by activating MAP-kinase pathway and decreasing Rho-GAP activity. J Biol Chem, 278:2807-2818, 2003.
Chen Y, Zhuang S, Cassenaer S, Casteel DE, Guid T, Boss GR, Pilz RB. Synergism between calcium and cGMP in CRE-dependent transcriptional regulation required cooperation between CREB and C/EBP-related β. Mol. Cell. Biol, 23:4066-4082, 2003.
Zhuang S, Nyugen GT, Chen Y, Gudi T, Eigenthaler M, Jarchau T, Walter U, Boss GR, Pilz RB. VASP-activation of SRE-dependent transcription occurs downstream of RhoA and is inhibited by cGMP-dependent protein kinase phosphorylation. J. Biol. Chem., 2004, 279:10379-10407.
Zhao X, Zhuang S, Chen Y, Boss GR, Pilz RB. Cyclic GMP-dependent protein kinase regulated CCAAT enhancer-binding protein β functions through inhibition of glycogen synthase kinase-3. J. Biol. Chem., 2005, 280:32683-92.
Casteel DE, Boss GR, Pilz RB. Identification of the interface between cGMP-dependent protein kinase Ibeta and its interaction partners TFII-I and IRAG reveals a common interaction motif. J. Biol. Che., 2005, 280:38211-38218.
Zeng Y, Zhuang S, Gloddek J, Tseng CC, Boss GR, Pilz RB. Regulation of cGMP-dependent protein kinase expression by Rho and Kruppel-like transcription factor-4. J. Ciol. Chem., 2006, 280:16951-16961.
Broderick KE, Zhang T, Rangaswami H, Zeng Y, Zhao X, Boss GR, Pilz RB. Cyclic GMP-cGMP-dependent protein kinase induced interleukin-6 transcription in osteoblasts. Mol. Endocrinol., 2007, 21:1148-62.
Zhang T, Zhuang S, Casteel ED, Looney DJ, Boss GR, Pilz GR. A cysteine-rich LIM-only protein mediates regulation of smooth muscle-specific gene expression by cGMP-dependent protein kinase. J. Biol. Chem., 2007, 282: 33367-80.
Turner SJ, Zhuang S, Zhang T, Boss GR, Pilz RB. Effects of lovastatin on Rho isoform expression, activity, and association with guanine nucleotide dissociation inhibitors. Biochem. Pharmacol., 2008, 75:405-13.
Casteel, DE, Zhang T, Zhuang, Pilz RB. cGMP-dependent protein kinase anchoring by IRAG regulates its nuclear translocation and transcriptional activity. Cell Signal, 2008, 20(7):1392-9.
