Larry Karnitz

Summary

Affiliation: Mayo Clinic
Country: USA

Publications

  1. doi request reprint Molecular Pathways: Targeting ATR in Cancer Therapy
    Larry M Karnitz
    Division of Oncology Research and Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, Minnesota
    Clin Cancer Res 21:4780-5. 2015
  2. pmc Sonic Hedgehog signaling impairs ionizing radiation-induced checkpoint activation and induces genomic instability
    Jennifer M Leonard
    Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN 55905, USA
    J Cell Biol 183:385-91. 2008
  3. pmc Checkpoint signaling, base excision repair, and PARP promote survival of colon cancer cells treated with 5-fluorodeoxyuridine but not 5-fluorouracil
    Liyi Geng
    Division of Oncology Research, Mayo Clinic, College of Medicine, Rochester, Minnesota, United States of America
    PLoS ONE 6:e28862. 2011
  4. pmc RAD18-mediated ubiquitination of PCNA activates the Fanconi anemia DNA repair network
    Liyi Geng
    Division of Oncology Research, Mayo Clinic College of Medicine, Rochester, MN 55905, USA
    J Cell Biol 191:249-57. 2010
  5. pmc Identification of DNA repair pathways that affect the survival of ovarian cancer cells treated with a poly(ADP-ribose) polymerase inhibitor in a novel drug combination
    Amelia M Huehls
    Division of Oncology Research, Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, College of Medicine, Rochester, Minnesota, USA
    Mol Pharmacol 82:767-76. 2012
  6. ncbi request reprint Cdc37 regulation of the kinome: when to hold 'em and when to fold 'em
    Larry M Karnitz
    Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic College of Medicine, Rochester, MN 55905, USA
    Sci STKE 2007:pe22. 2007
  7. ncbi request reprint Gemcitabine-induced activation of checkpoint signaling pathways that affect tumor cell survival
    Larry M Karnitz
    Division of Oncology Research, Guggenheim 13, Mayo Clinic College of Medicine, 200 First Street, S W, Rochester, Minnesota 55905, USA
    Mol Pharmacol 68:1636-44. 2005
  8. ncbi request reprint Hsp90 inhibition depletes Chk1 and sensitizes tumor cells to replication stress
    Sonnet J H Arlander
    Department of Molecular Pharmacology, Mayo Graduate School, Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA
    J Biol Chem 278:52572-7. 2003
  9. ncbi request reprint Dial 9-1-1 for DNA damage: the Rad9-Hus1-Rad1 (9-1-1) clamp complex
    Edgardo R Parrilla-Castellar
    Tumor Biology Program, Mayo Clinic College of Medicine, Rochester, MN 55905, USA
    DNA Repair (Amst) 3:1009-14. 2004
  10. pmc Cisplatin-induced DNA damage activates replication checkpoint signaling components that differentially affect tumor cell survival
    Jill M Wagner
    Department of Molecular Pharmacology and Experimental Therapeutics and Division of Oncology Research, Mayo Clinic, College of Medicine, Rochester, MN 55905, USA
    Mol Pharmacol 76:208-14. 2009

Research Grants

Collaborators

  • Scott Kaufmann
  • HOWARD LIEBERMAN
  • C Erlichman
  • S J Felts
  • Lee Zou
  • Cynthia Wetmore
  • Junjie Chen
  • Paul Haluska
  • William Cliby
  • Judith E Karp
  • Jill M Wagner
  • Benjamin T Vroman
  • Catherine J Huntoon
  • Liyi Geng
  • Sonnet J H Arlander
  • Amelia M Huehls
  • Pia Roos-Mattjus
  • David Loegering
  • Edgardo R Parrilla-Castellar
  • Nga T Dai
  • Karen Flatten
  • Matthew A Burtelow
  • Karen S Flatten
  • Jennifer M Leonard
  • Marina Galvez-Peralta
  • Sinny Delacroix
  • David J Matthews
  • Ruben A Mesa
  • David O Toft
  • Jennifer S Hackbarth
  • Kevin M Hopkins
  • Vanessa M Dufault
  • Andrea J Oestreich
  • Carolin J Merkle
  • Alex K Eapen
  • Monica D Nye
  • Kevin L Peterson
  • Stephanie L Safgren
  • David A Loegering
  • Hong Ye
  • Matthew M Ames
  • Yong D Kim
  • F Michael Yakes
  • Nicole Miller
  • Michele Tadano
  • Douglas O Clary
  • Albert Tai
  • Ken ichi Yamamoto
  • Louis Murray
  • Lester Bornheim
  • Scott Robertson
  • Masahiko Kobayashi
  • Bridget Stensgard
  • Heather L Powell
  • B Douglas Smith
  • Cynthia J Ten Eyck
  • Michael P Heldebrant
  • Sun Hee Lee
  • Xue Wei Meng
  • Jennifer Hackbarth
  • Vladimir N Podust
  • John T Henry-S├ínchez
  • Kenneth L Johnson
  • Robert J McDonald
  • Stephen Naylor
  • Matthew Rauen

Detail Information

Publications26

  1. doi request reprint Molecular Pathways: Targeting ATR in Cancer Therapy
    Larry M Karnitz
    Division of Oncology Research and Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, Minnesota
    Clin Cancer Res 21:4780-5. 2015
    ..These trials will generate important insights into the effects of ATR inhibition in humans and the potential role of inhibiting this kinase in the treatment of human malignancies...
  2. pmc Sonic Hedgehog signaling impairs ionizing radiation-induced checkpoint activation and induces genomic instability
    Jennifer M Leonard
    Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN 55905, USA
    J Cell Biol 183:385-91. 2008
    ..These results suggest that inappropriate Shh pathway activation promotes tumorigenesis by disabling a key signaling pathway that helps maintain genomic stability and inhibits tumorigenesis...
  3. pmc Checkpoint signaling, base excision repair, and PARP promote survival of colon cancer cells treated with 5-fluorodeoxyuridine but not 5-fluorouracil
    Liyi Geng
    Division of Oncology Research, Mayo Clinic, College of Medicine, Rochester, Minnesota, United States of America
    PLoS ONE 6:e28862. 2011
    ....
  4. pmc RAD18-mediated ubiquitination of PCNA activates the Fanconi anemia DNA repair network
    Liyi Geng
    Division of Oncology Research, Mayo Clinic College of Medicine, Rochester, MN 55905, USA
    J Cell Biol 191:249-57. 2010
    ..Collectively, these experiments identify RAD18-mediated PCNA monoubiquitination as a central hub for the mobilization of the FA pathway by promoting FANCL-mediated FANCD2 monoubiquitylation...
  5. pmc Identification of DNA repair pathways that affect the survival of ovarian cancer cells treated with a poly(ADP-ribose) polymerase inhibitor in a novel drug combination
    Amelia M Huehls
    Division of Oncology Research, Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, College of Medicine, Rochester, Minnesota, USA
    Mol Pharmacol 82:767-76. 2012
    ....
  6. ncbi request reprint Cdc37 regulation of the kinome: when to hold 'em and when to fold 'em
    Larry M Karnitz
    Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic College of Medicine, Rochester, MN 55905, USA
    Sci STKE 2007:pe22. 2007
    ..However, new evidence suggests that most kinases do require chaperoning and, furthermore, that Cdc37, a chaperone that has Hsp90-dependent and -independent functions, serves as the chaperone for a large portion of the yeast kinome...
  7. ncbi request reprint Gemcitabine-induced activation of checkpoint signaling pathways that affect tumor cell survival
    Larry M Karnitz
    Division of Oncology Research, Guggenheim 13, Mayo Clinic College of Medicine, 200 First Street, S W, Rochester, Minnesota 55905, USA
    Mol Pharmacol 68:1636-44. 2005
    ....
  8. ncbi request reprint Hsp90 inhibition depletes Chk1 and sensitizes tumor cells to replication stress
    Sonnet J H Arlander
    Department of Molecular Pharmacology, Mayo Graduate School, Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA
    J Biol Chem 278:52572-7. 2003
    ..Collectively, our studies identify Chk1 as a novel Hsp90 client and suggest that pharmacologic inhibition of Hsp90 may sensitize tumor cells to chemotherapeutic agents by disrupting Chk1 function during replication stress...
  9. ncbi request reprint Dial 9-1-1 for DNA damage: the Rad9-Hus1-Rad1 (9-1-1) clamp complex
    Edgardo R Parrilla-Castellar
    Tumor Biology Program, Mayo Clinic College of Medicine, Rochester, MN 55905, USA
    DNA Repair (Amst) 3:1009-14. 2004
    ..Taken together, these findings suggest that the 9-1-1 clamp is a multifunctional complex that is loaded onto DNA at sites of damage, where it coordinates checkpoint activation and DNA repair...
  10. pmc Cisplatin-induced DNA damage activates replication checkpoint signaling components that differentially affect tumor cell survival
    Jill M Wagner
    Department of Molecular Pharmacology and Experimental Therapeutics and Division of Oncology Research, Mayo Clinic, College of Medicine, Rochester, MN 55905, USA
    Mol Pharmacol 76:208-14. 2009
    ..In fact, Chk1 depletion reversed the sensitivity seen when Rad18 was disabled. Collectively, these studies suggest that the pharmacological manipulation of Chk1 may not be an effective strategy to sensitize tumors to platinating agents...
  11. pmc Heat shock protein 90 inhibition depletes LATS1 and LATS2, two regulators of the mammalian hippo tumor suppressor pathway
    Catherine J Huntoon
    Division of Oncology Research, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA
    Cancer Res 70:8642-50. 2010
    ..Taken together, these results identify LATS1 and LATS2 as novel HSP90 clients and show that HSP90 inhibitors can disrupt the LATS tumor suppressor pathway in human cancer cells...
  12. pmc Functioning of the Hsp90 machine in chaperoning checkpoint kinase I (Chk1) and the progesterone receptor (PR)
    Sara J Felts
    Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA
    Cell Stress Chaperones 12:353-63. 2007
    ..Importantly, the cochaperones Hop and Cdc37 cooperate as the kinase transitions from immature Hsp70- to mature Hsp90-predominant complexes...
  13. ncbi request reprint Cloning and characterization of hCTF18, hCTF8, and hDCC1. Human homologs of a Saccharomyces cerevisiae complex involved in sister chromatid cohesion establishment
    Carolin J Merkle
    Graduate Program in Tumor Biology, Mayo Graduate School, Rochester, Minnesota 55905, USA
    J Biol Chem 278:30051-6. 2003
    ..Our data provide evidence for the existence of an alternative RFC complex with a probable role in mammalian sister chromatid cohesion establishment...
  14. ncbi request reprint The role of checkpoint kinase 1 in sensitivity to topoisomerase I poisons
    Karen Flatten
    Division of Oncology Research, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA
    J Biol Chem 280:14349-55. 2005
    ..Collectively, these results show that the ATR/Chk1 pathway plays a predominant role in the response to topoisomerase I inhibitors in carcinoma cells and identify a potential approach for enhancing the efficacy of these drugs...
  15. pmc Heat shock protein 90 inhibition sensitizes acute myelogenous leukemia cells to cytarabine
    Ruben A Mesa
    Division of Hematology, Department of Medicine, Mayo Clinic College of Medicine, Rochester, MN 55905, USA
    Blood 106:318-27. 2005
    ..Collectively, these results suggest that treatment with 17-AAG might represent a means of reversing checkpoint-mediated cytarabine resistance in AML...
  16. pmc Overcoming S-phase checkpoint-mediated resistance: sequence-dependent synergy of gemcitabine and 7-ethyl-10-hydroxycamptothecin (SN-38) in human carcinoma cell lines
    Marina Galvez-Peralta
    Division of Oncology Research and Department of Molecular Pharmacology, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA
    Mol Pharmacol 74:724-35. 2008
    ..These results collectively suggest that S-phase-selective agents might exhibit more cytotoxicity when administered sequentially rather than simultaneously...
  17. pmc The Rad9-Hus1-Rad1 (9-1-1) clamp activates checkpoint signaling via TopBP1
    Sinny Delacroix
    Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA
    Genes Dev 21:1472-7. 2007
    ....
  18. ncbi request reprint Genotoxin-induced Rad9-Hus1-Rad1 (9-1-1) chromatin association is an early checkpoint signaling event
    Pia Roos-Mattjus
    Department of Biochemistry and Molecular Biology, Mayo Graduate School, Rochester, Minnesota 55905, USA
    J Biol Chem 277:43809-12. 2002
    ..Collectively, these studies demonstrate that 9-1-1 chromatin binding is a proximal event in the checkpoint signaling cascade...
  19. ncbi request reprint Cut5 is required for the binding of Atr and DNA polymerase alpha to genotoxin-damaged chromatin
    Edgardo R Parrilla-Castellar
    Tumor Biology Program, Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA
    J Biol Chem 278:45507-11. 2003
    ..Taken together, these results demonstrate that Cut5 plays an integral role in the recruitment and assembly of the Chk1 signaling cascade components following DNA damage...
  20. ncbi request reprint Rad9 protects cells from topoisomerase poison-induced cell death
    David Loegering
    Division of Oncology Research, Mayo Clinic, Rochester, Minnesota 55905, USA
    J Biol Chem 279:18641-7. 2004
    ..Collectively, these results suggest that the predominant role of Rad9 in ES cells is to promote survival after replicative stress and topoisomerase-mediated DNA damage...
  21. ncbi request reprint Identification and characterization of RAD9B, a paralog of the RAD9 checkpoint gene
    Vanessa M Dufault
    Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic and Foundation, Rochester, MN 55905, USA
    Genomics 82:644-51. 2003
    ..Taken together, these results suggest that these proteins can combinatorially assemble into distinct 9-1-1 clamps that may have distinct biological functions...
  22. ncbi request reprint Phosphorylation of human Rad9 is required for genotoxin-activated checkpoint signaling
    Pia Roos-Mattjus
    Department of Biochemistry and Molecular Biology, Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA
    J Biol Chem 278:24428-37. 2003
    ..Collectively, these results demonstrate that the Rad9 phospho-tail is a key participant in the Chk1 activation pathway and point to additional roles for Rad9 in cellular responses to IR...
  23. ncbi request reprint S-peptide epitope tagging for protein purification, expression monitoring, and localization in mammalian cells
    Jennifer S Hackbarth
    Mayo Clinic College of Medicine, Rochester, MN 55905, USA
    Biotechniques 37:835-9. 2004
    ..These reagents make the S-peptide/S-protein system an attractive alternative to currently available epitope tagging methods...
  24. ncbi request reprint Purification and identification of protein complexes that control the cell cycle
    Matthew A Burtelow
    Division of Oncology Research, Mayo Clinic, Rochester, MN, USA
    Methods Mol Biol 241:247-53. 2004
  25. ncbi request reprint Pharmacological abrogation of S-phase checkpoint enhances the anti-tumor activity of gemcitabine in vivo
    David J Matthews
    Exelixis Inc, South San Francisco, California 94083, USA
    Cell Cycle 6:104-10. 2007
    ..Together, these data show that cell cycle checkpoint inhibitors may have significant clinical utility in potentiating the activity of gemcitabine...
  26. ncbi request reprint Chaperoning checkpoint kinase 1 (Chk1), an Hsp90 client, with purified chaperones
    Sonnet J H Arlander
    Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Graduate School
    J Biol Chem 281:2989-98. 2006
    ....

Research Grants2

  1. Analysis of a DNA Damage-Inducible Checkpoint Complex
    Larry Karnitz; Fiscal Year: 2008
    ..Collectively, these studies will provide new insights into how the 911 complexes direct downstream events that regulate checkpoint activation, cell survival, and genomic stability. [unreadable] [unreadable]..
  2. Therapeutic targeting of HSP90-dependent signaling
    Larry Karnitz; Fiscal Year: 2008
    ..Collectively, these studies will provide information about the ability to alter the response of ovarian cancer cells to chemotherapeutic agents in vitro and in the clinical setting. [unreadable] [unreadable]..