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Renate Pilz

Title(s)Professor In Residence, Medicine
SchoolHealth Sciences
Phone858-534-8805
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    Collapse Overview 
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    Research Interests
    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

    Collapse Research 
    Collapse Research Activities and Funding
    Targeting defective NO/cGMP signaling as novel therapy for diabetic osteoporosis
    NIH/NIAMS R01AR068601Apr 1, 2016 - Mar 31, 2021
    Role: Principal Investigator
    Mechanisms of vascular pathology from abnormal protein kinase G signaling
    NIH/NHLBI R01HL132141Apr 1, 2016 - Jan 31, 2020
    Role: Principal Investigator
    Testing novel NO/cGMP-based bone-anabolic agents in mouse models of osteoporosis
    NIH/NIAMS R21AR065658Jul 10, 2015 - Apr 30, 2017
    Role: Principal Investigator
    cGMP-dependent Protein Kinase Function in Osteoblast Mechanotransduction
    NIH/NIAMS R01AR051300Sep 1, 1998 - May 31, 2015
    Role: Principal Investigator
    REGULATION OF GENE EXPRESSION BY NO/CGMP
    NIH/NIGMS R01GM055586Sep 1, 1998 - Aug 31, 2004
    Role: Principal Investigator
    G KINASE AND DIFFERENTIATION--USE OF HL-60 MUTANT
    NIH/NCI K08CA001548Aug 16, 1990 - Jul 31, 1995
    Role: Principal Investigator

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    Collapse Bibliographic 
    Collapse Publications
    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Researchers can login to make corrections and additions, or contact us for help.
    List All   |   Timeline
    1. Ramdani G, Schall N, Kalyanaraman H, Wahwah N, Moheize S, Lee JJ, Sah RL, Pfeifer A, Casteel DE, Pilz RB. cGMP-dependent protein kinase-2 regulates bone mass and prevents diabetic bone loss. J Endocrinol. 2018 Sep; 238(3):203-219. PMID: 29914933.
      View in: PubMed
    2. Kalyanaraman H, Schall N, Pilz RB. Nitric oxide and cyclic GMP functions in bone. Nitric Oxide. 2018 Jun 01; 76:62-70. PMID: 29550520.
      View in: PubMed
    3. Kalyanaraman H, Schwaerzer G, Ramdani G, Castillo F, Scott BT, Dillmann W, Sah RL, Casteel DE, Pilz RB. Protein Kinase G Activation Reverses Oxidative Stress and Restores Osteoblast Function and Bone Formation in Male Mice With Type 1 Diabetes. Diabetes. 2018 04; 67(4):607-623. PMID: 29301852.
      View in: PubMed
    4. Kalyanaraman H, Zhuang S, Pilz RB, Casteel DE. The activity of cGMP-dependent protein kinase Ia is not directly regulated by oxidation-induced disulfide formation at cysteine 43. J Biol Chem. 2017 05 19; 292(20):8262-8268. PMID: 28360102.
      View in: PubMed
    5. Bebarta VS, Brittain M, Chan A, Garrett N, Yoon D, Burney T, Mukai D, Babin M, Pilz RB, Mahon SB, Brenner M, Boss GR. Sodium Nitrite and Sodium Thiosulfate Are Effective Against Acute Cyanide Poisoning When Administered by Intramuscular Injection. Ann Emerg Med. 2017 Jun; 69(6):718-725.e4. PMID: 28041825.
      View in: PubMed
    6. Kalyanaraman H, Ramdani G, Joshua J, Schall N, Boss GR, Cory E, Sah RL, Casteel DE, Pilz RB. A Novel, Direct NO Donor Regulates Osteoblast and Osteoclast Functions and Increases Bone Mass in Ovariectomized Mice. J Bone Miner Res. 2017 01; 32(1):46-59. PMID: 27391172.
      View in: PubMed
    7. Jiang J, Chan A, Ali S, Saha A, Haushalter KJ, Lam WL, Glasheen M, Parker J, Brenner M, Mahon SB, Patel HH, Ambasudhan R, Lipton SA, Pilz RB, Boss GR. Hydrogen Sulfide--Mechanisms of Toxicity and Development of an Antidote. Sci Rep. 2016 Feb 15; 6:20831. PMID: 26877209.
      View in: PubMed
    8. Chan A, Jiang J, Fridman A, Guo LT, Shelton GD, Liu MT, Green C, Haushalter KJ, Patel HH, Lee J, Yoon D, Burney T, Mukai D, Mahon SB, Brenner M, Pilz RB, Boss GR. Nitrocobinamide, a new cyanide antidote that can be administered by intramuscular injection. J Med Chem. 2015 Feb 26; 58(4):1750-9. PMID: 25650735; PMCID: PMC4494098.
    9. Joshua J, Schwaerzer GK, Kalyanaraman H, Cory E, Sah RL, Li M, Vaida F, Boss GR, Pilz RB. Soluble guanylate cyclase as a novel treatment target for osteoporosis. Endocrinology. 2014 Dec; 155(12):4720-30. PMID: 25188528; PMCID: PMC4239425.
    10. Saha A, Connelly S, Jiang J, Zhuang S, Amador DT, Phan T, Pilz RB, Boss GR. Akt phosphorylation and regulation of transketolase is a nodal point for amino acid control of purine synthesis. Mol Cell. 2014 Jul 17; 55(2):264-76. PMID: 24981175; PMCID: PMC4104231.
    11. Kalyanaraman H, Schwappacher R, Joshua J, Zhuang S, Scott BT, Klos M, Casteel DE, Frangos JA, Dillmann W, Boss GR, Pilz RB. Nongenomic thyroid hormone signaling occurs through a plasma membrane-localized receptor. Sci Signal. 2014 May 20; 7(326):ra48. PMID: 24847117.
      View in: PubMed
    12. Yan M, Dong Z, Zhao F, Chauncey T, Deauna-Limayo D, Wang-Rodriguez J, Liu D, Wang HY, Pilz R. CD20-positive plasmablastic lymphoma with excellent response to bortezomib combined with rituximab. Eur J Haematol. 2014 Jul; 93(1):77-80. PMID: 24528507.
      View in: PubMed
    13. Joshua J, Kalyanaraman H, Marathe N, Pilz RB. Nitric oxide as a mediator of estrogen effects in osteocytes. Vitam Horm. 2014; 96:247-63. PMID: 25189390.
      View in: PubMed
    14. Fridman A, Saha A, Chan A, Casteel DE, Pilz RB, Boss GR. Cell cycle regulation of purine synthesis by phosphoribosyl pyrophosphate and inorganic phosphate. Biochem J. 2013 Aug 15; 454(1):91-9. PMID: 23734909.
      View in: PubMed
    15. Spitler R, Schwappacher R, Wu T, Kong X, Yokomori K, Pilz RB, Boss GR, Berns MW. Nitrosyl-cobinamide (NO-Cbi), a new nitric oxide donor, improves wound healing through cGMP/cGMP-dependent protein kinase. Cell Signal. 2013 Dec; 25(12):2374-82. PMID: 23920342.
      View in: PubMed
    16. Schwappacher R, Kilic A, Kojonazarov B, Lang M, Diep T, Zhuang S, Gawlowski T, Schermuly RT, Pfeifer A, Boss GR, Pilz RB. A molecular mechanism for therapeutic effects of cGMP-elevating agents in pulmonary arterial hypertension. J Biol Chem. 2013 Jun 07; 288(23):16557-66. PMID: 23612967; PMCID: PMC3675591.
    17. Casteel DE, Turner S, Schwappacher R, Rangaswami H, Su-Yuo J, Zhuang S, Boss GR, Pilz RB. Rho isoform-specific interaction with IQGAP1 promotes breast cancer cell proliferation and migration. J Biol Chem. 2012 Nov 02; 287(45):38367-78. PMID: 22992742; PMCID: PMC3488105.
    18. Rangaswami H, Schwappacher R, Tran T, Chan GC, Zhuang S, Boss GR, Pilz RB. Protein kinase G and focal adhesion kinase converge on Src/Akt/ß-catenin signaling module in osteoblast mechanotransduction. J Biol Chem. 2012 Jun 15; 287(25):21509-19. PMID: 22563076; PMCID: PMC3375572.
    19. Marathe N, Rangaswami H, Zhuang S, Boss GR, Pilz RB. Pro-survival effects of 17ß-estradiol on osteocytes are mediated by nitric oxide/cGMP via differential actions of cGMP-dependent protein kinases I and II. J Biol Chem. 2012 Jan 06; 287(2):978-88. PMID: 22117068; PMCID: PMC3256896.
    20. Chan A, Crankshaw DL, Monteil A, Patterson SE, Nagasawa HT, Briggs JE, Kozocas JA, Mahon SB, Brenner M, Pilz RB, Bigby TD, Boss GR. The combination of cobinamide and sulfanegen is highly effective in mouse models of cyanide poisoning. Clin Toxicol (Phila). 2011 Jun; 49(5):366-73. PMID: 21740135; PMCID: PMC3882312.
    21. Rangaswami H, Schwappacher R, Marathe N, Zhuang S, Casteel DE, Haas B, Chen Y, Pfeifer A, Kato H, Shattil S, Boss GR, Pilz RB. Cyclic GMP and protein kinase G control a Src-containing mechanosome in osteoblasts. Sci Signal. 2010 Dec 21; 3(153):ra91. PMID: 21177494; PMCID: PMC3093297.
    22. Casteel DE, Smith-Nguyen EV, Sankaran B, Roh SH, Pilz RB, Kim C. A crystal structure of the cyclic GMP-dependent protein kinase I{beta} dimerization/docking domain reveals molecular details of isoform-specific anchoring. J Biol Chem. 2010 Oct 22; 285(43):32684-8. PMID: 20826808.
      View in: PubMed
    23. Blackledge WC, Blackledge CW, Griesel A, Mahon SB, Brenner M, Pilz RB, Boss GR. New facile method to measure cyanide in blood. Anal Chem. 2010 May 15; 82(10):4216-21. PMID: 20420400; PMCID: PMC2889625.
    24. Rangaswami H, Marathe N, Zhuang S, Chen Y, Yeh JC, Frangos JA, Boss GR, Pilz RB. Type II cGMP-dependent protein kinase mediates osteoblast mechanotransduction. J Biol Chem. 2009 May 29; 284(22):14796-808. PMID: 19282289; PMCID: PMC2685661.
    25. Casteel DE, Zhuang S, Zeng Y, Perrino FW, Boss GR, Goulian M, Pilz RB. A DNA polymerase-{alpha}{middle dot}primase cofactor with homology to replication protein A-32 regulates DNA replication in mammalian cells. J Biol Chem. 2009 Feb 27; 284(9):5807-18. PMID: 19119139; PMCID: PMC2645831.
    26. Wang W, Fridman A, Blackledge W, Connelly S, Wilson IA, Pilz RB, Boss GR. The phosphatidylinositol 3-kinase/akt cassette regulates purine nucleotide synthesis. J Biol Chem. 2009 Feb 06; 284(6):3521-8. PMID: 19068483; PMCID: PMC2635033.
    27. Casteel DE, Zhang T, Zhuang S, Pilz RB. cGMP-dependent protein kinase anchoring by IRAG regulates its nuclear translocation and transcriptional activity. Cell Signal. 2008 Jul; 20(7):1392-9. PMID: 18450420; PMCID: PMC2477739.
    28. Broderick KE, Chan A, Balasubramanian M, Feala J, Reed SL, Panda M, Sharma VS, Pilz RB, Bigby TD, Boss GR. Cyanide produced by human isolates of Pseudomonas aeruginosa contributes to lethality in Drosophila melanogaster. J Infect Dis. 2008 Feb 01; 197(3):457-64. PMID: 18199034.
      View in: PubMed
    29. Broderick KE, Alvarez L, Balasubramanian M, Belke DD, Makino A, Chan A, Woods VL, Dillmann WH, Sharma VS, Pilz RB, Bigby TD, Boss GR. Nitrosyl-cobinamide, a new and direct nitric oxide releasing drug effective in vivo. Exp Biol Med (Maywood). 2007 Dec; 232(11):1432-40. PMID: 18040067.
      View in: PubMed
    30. Zhang T, Zhuang S, Casteel DE, Looney DJ, Boss GR, Pilz RB. A cysteine-rich LIM-only protein mediates regulation of smooth muscle-specific gene expression by cGMP-dependent protein kinase. J Biol Chem. 2007 Nov 16; 282(46):33367-80. PMID: 17878170.
      View in: PubMed
    31. 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 Jan 15; 75(2):405-13. PMID: 17920041; PMCID: PMC2228324.
    32. Broderick KE, Balasubramanian M, Chan A, Potluri P, Feala J, Belke DD, McCulloch A, Sharma VS, Pilz RB, Bigby TD, Boss GR. The cobalamin precursor cobinamide detoxifies nitroprusside-generated cyanide. Exp Biol Med (Maywood). 2007 Jun; 232(6):789-98. PMID: 17526771.
      View in: PubMed
    33. Broderick KE, Zhang T, Rangaswami H, Zeng Y, Zhao X, Boss GR, Pilz RB. Guanosine 3',5'-cyclic monophosphate (cGMP)/cGMP-dependent protein kinase induce interleukin-6 transcription in osteoblasts. Mol Endocrinol. 2007 May; 21(5):1148-62. PMID: 17341596.
      View in: PubMed
    34. Broderick KE, Feala J, McCulloch A, Paternostro G, Sharma VS, Pilz RB, Boss GR. The nitric oxide scavenger cobinamide profoundly improves survival in a Drosophila melanogaster model of bacterial sepsis. FASEB J. 2006 Sep; 20(11):1865-73. PMID: 16940158.
      View in: PubMed
    35. Broderick KE, Potluri P, Zhuang S, Scheffler IE, Sharma VS, Pilz RB, Boss GR. Cyanide detoxification by the cobalamin precursor cobinamide. Exp Biol Med (Maywood). 2006 May; 231(5):641-9. PMID: 16636313.
      View in: PubMed
    36. 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 Biol Chem. 2006 Jun 23; 281(25):16951-61. PMID: 16632465.
      View in: PubMed
    37. 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 Chem. 2005 Nov 18; 280(46):38211-8. PMID: 16166082.
      View in: PubMed
    38. Zhao X, Zhuang S, Chen Y, Boss GR, Pilz RB. Cyclic GMP-dependent protein kinase regulates CCAAT enhancer-binding protein beta functions through inhibition of glycogen synthase kinase-3. J Biol Chem. 2005 Sep 23; 280(38):32683-92. PMID: 16055922.
      View in: PubMed
    39. Pilz RB, Broderick KE. Role of cyclic GMP in gene regulation. Front Biosci. 2005 May 01; 10:1239-68. PMID: 15769622.
      View in: PubMed
    40. Kambo A, Sharma VS, Casteel DE, Woods VL, Pilz RB, Boss GR. Nitric oxide inhibits mammalian methylmalonyl-CoA mutase. J Biol Chem. 2005 Mar 18; 280(11):10073-82. PMID: 15647267.
      View in: PubMed
    41. Broderick KE, Singh V, Zhuang S, Kambo A, Chen JC, Sharma VS, Pilz RB, Boss GR. Nitric oxide scavenging by the cobalamin precursor cobinamide. J Biol Chem. 2005 Mar 11; 280(10):8678-85. PMID: 15632180.
      View in: PubMed
    42. Zhuang S, Nguyen GT, Chen Y, Gudi T, Eigenthaler M, Jarchau T, Walter U, Boss GR, Pilz RB. Vasodilator-stimulated phosphoprotein activation of serum-response element-dependent transcription occurs downstream of RhoA and is inhibited by cGMP-dependent protein kinase phosphorylation. J Biol Chem. 2004 Mar 12; 279(11):10397-407. PMID: 14679200.
      View in: PubMed
    43. Pilz RB, Casteel DE. Regulation of gene expression by cyclic GMP. Circ Res. 2003 Nov 28; 93(11):1034-46. PMID: 14645134.
      View in: PubMed
    44. Sharma VS, Pilz RB, Boss GR, Magde D. Reactions of nitric oxide with vitamin B12 and its precursor, cobinamide. Biochemistry. 2003 Jul 29; 42(29):8900-8. PMID: 12873151.
      View in: PubMed
    45. Chen Y, Zhuang S, Cassenaer S, Casteel DE, Gudi T, Boss GR, Pilz RB. Synergism between calcium and cyclic GMP in cyclic AMP response element-dependent transcriptional regulation requires cooperation between CREB and C/EBP-beta. Mol Cell Biol. 2003 Jun; 23(12):4066-82. PMID: 12773552; PMCID: PMC156132.
    46. Chen JC, Zhuang S, Nguyen TH, Boss GR, Pilz RB. Oncogenic Ras leads to Rho activation by activating the mitogen-activated protein kinase pathway and decreasing Rho-GTPase-activating protein activity. J Biol Chem. 2003 Jan 31; 278(5):2807-18. PMID: 12429740.
      View in: PubMed
    47. Im E, von Lintig FC, Chen J, Zhuang S, Qui W, Chowdhury S, Worley PF, Boss GR, Pilz RB. Rheb is in a high activation state and inhibits B-Raf kinase in mammalian cells. Oncogene. 2002 Sep 12; 21(41):6356-65. PMID: 12214276.
      View in: PubMed
    48. Gudi T, Chen JC, Casteel DE, Seasholtz TM, Boss GR, Pilz RB. cGMP-dependent protein kinase inhibits serum-response element-dependent transcription by inhibiting rho activation and functions. J Biol Chem. 2002 Oct 04; 277(40):37382-93. PMID: 12119292.
      View in: PubMed
    49. Casteel DE, Zhuang S, Gudi T, Tang J, Vuica M, Desiderio S, Pilz RB. cGMP-dependent protein kinase I beta physically and functionally interacts with the transcriptional regulator TFII-I. J Biol Chem. 2002 Aug 30; 277(35):32003-14. PMID: 12082086.
      View in: PubMed