Research Topics
| KENNETH contact KAUSHANSKYSummaryAffiliation: University of California Country: USA Publications
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Detail Information
Publications
Deletion of the extracellular membrane-distal cytokine receptor homology module of Mpl results in constitutive cell growth and loss of thrombopoietin bindingD F Sabath
Department of Medicine, University of Washington, Seattle, WA 98195, USA
Blood 94:365-7. 1999..Both mutant receptors failed to bind 125I-Tpo. These results suggest that the membrane-distal CRM of Mpl acts as a brake on cell proliferation and that this region is required for ligand binding...- Tyrosine 462 of the membrane-proximal F'-G' loop of murine Mpl is not essential for high-affinity binding of thrombopoietinD F Sabath
Department of Medicine, University of Washington, Seattle, WA 98195, USA
Cytokine 12:127-33. 2000..This study suggests that unlike the corresponding Tyr(421)of the common human beta chain, Tyr(462)of murine Mpl is not required for high-affinity ligand binding, although it may be located in proximity to the ligand binding site... - Thrombopoietin (TPO) induces c-myc expression through a PI3K- and MAPK-dependent pathway that is not mediated by Akt, PKCzeta or mTOR in TPO-dependent cell lines and primary megakaryocytesSupantitra Chanprasert
Department of Clinical Microscopy, Faculty of Medical Technology, Mahidol University, Bangkok, Thailand
Cell Signal 18:1212-8. 2006..Therefore, we conclude that TPO stimulates c-myc expression in primary megakaryocytes through a PI3K- and MAPK-dependent pathway that is not mediated by Akt, PKCzeta or mTOR... - Endomitotic megakaryocytes form a midzone in anaphase but have a deficiency in cleavage furrow formationAmy E Geddis
Department of Pediatrics, Hematology-Oncology, University of California San Diego, San Diego, California, USA. ageddis@ ucsd.edu
Cell Cycle 5:538-45. 2006..This work explores the mechanism of a normally occurring furrowing defect in a nonmalignant primary cell... 
YRRL motifs in the cytoplasmic domain of the thrombopoietin receptor regulate receptor internalization and degradationIan S Hitchcock
Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA
Blood 112:2222-31. 2008..Our data establishes that c-Mpl cytoplasmic YRRL motifs are responsible for both Tpo-mediated internalization via interactions with AP2 and lysosomal targeting after endocytosis...- The chronic myeloproliferative disorders and mutation of JAK2: Dameshek's 54 year old speculation comes of ageKenneth Kaushansky
Department of Medicine, Division of Hematology Oncology, University of California, San Diego, 402 Dickinson Street, Suite 380, CA 92103 8811, USA
Best Pract Res Clin Haematol 20:5-12. 2007.... - Thrombopoietin: accumulating evidence for an important biological effect on the hematopoietic stem cellKenneth Kaushansky
Department of Medicine, University of California, San Diego, San Diego, California 92103, USA
Ann N Y Acad Sci 996:39-43. 2003..Although the molecular mechanisms responsible for these findings are only now being explored, it is expected that a greater understanding of the roles played by TPO in HSC physiology will lead to novel therapeutic opportunities... - Thrombopoietin: a tool for understanding thrombopoiesisK Kaushansky
Department of Medicine, University of California San Diego, San Diego, CA, USA
J Thromb Haemost 1:1587-92. 2003..This review will focus on our current understanding of these processes... - Thrombopoietin and the hematopoietic stem cellKenneth Kaushansky
Department of Medicine, 402 Dickinson Street, Suite 380, San Diego, CA 92103 8811, USA
Ann N Y Acad Sci 1044:139-41. 2005..We found that TPO enhances the transcription of HoxB4, induces the nuclear localization of HoxA9, and upregulates VEGF expression by reducing the ubiquination of hypoxia inducible factor... - Historical review: megakaryopoiesis and thrombopoiesisKenneth Kaushansky
Department of Medicine, University of California, San Diego, CA 92103 8811, USA
Blood 111:981-6. 2008.... 
Molecular mechanisms of thrombopoietin signalingK Kaushansky
Department of Medicine, University of California, San Diego, La Jolla, CA 92093 0671, USA
J Thromb Haemost 7:235-8. 2009..This review will focus on these pathways in normal and neoplastic hematopoiesis...- Bloodlines: the importance of mentoring for the future of hematologyKenneth Kaushansky
Department of Medicine, University of California San Diego 92103-8811, La Jolla, USA
Blood 109:1353-4. 2007 - Immunology. The root of platelet productionAmy E Geddis
Departments of Pediatrics and Medicine, University of California, San Diego, CA 92103-8811, USA
Science 317:1689-91. 2007 - ASCI Presidential Address: Mentoring and teaching clinical investigationKenneth Kaushansky
Department of Medicine, University of California, San Diego, CA 92103-8811, USA
J Clin Invest 114:1165-8. 2004 - The molecular mechanisms that control thrombopoiesisKenneth Kaushansky
Department of Medicine, Division of Hematology Oncology, University of California, San Diego, California 92103 3931, USA
J Clin Invest 115:3339-47. 2005.... - Mpl and the hematopoietic stem cellK Kaushansky
Department of Medicine, Division of Hematology, University of Washington School of Medicine, Seattle, WA 98195, USA
Leukemia 16:738-9. 2002 - Phosphatidylinositol 3-kinase is necessary but not sufficient for thrombopoietin-induced proliferation in engineered Mpl-bearing cell lines as well as in primary megakaryocytic progenitorsA E Geddis
Division of Hematology, Department of Medicine, University of Washington, Seattle, Washington 98195-7710, USA
J Biol Chem 276:34473-9. 2001..Phosphatidylinositol 3-kinase activity is likely to be involved in regulating the G(1)/S transition... - Thrombopoietin, the ligand for the Mpl receptor, synergizes with steel factor and other early acting cytokines in supporting proliferation of primitive hematopoietic progenitors of miceH Ku
Department of Medicine, Medical University of South Carolina, Charleston, USA
Blood 87:4544-51. 1996..Based on these observations, we propose that ML can function as an early acting cytokine and stimulate the proliferation of cell cycle dormant progenitors by shortening their G0 period... - Thrombopoietin, the c-mpl ligand, is a major regulator of platelet productionV C Broudy
Department of Medicine, University of Washington, Seattle 98195, USA
J Leukoc Biol 57:719-25. 1995..This study outlines the cloning and biological characterization in vitro and in vivo of thrombopoietin, a major regulator of platelet production... - Kinetics of endomitosis in primary murine megakaryocytesC E Carow
Department of Medicine, University of Washington, Seattle 98195 7710, USA
J Cell Physiol 188:291-303. 2001.... - Cloning of human Bcl-2 homologue: inflammatory cytokines induce human A1 in cultured endothelial cellsA Karsan
Department of Medicine, Division of Hematology, University of Washington, Seattle, 98195, USA
Blood 87:3089-96. 1996..Additionally, vascular smooth muscle cells and various nonhematopoietic tissues express human Al, indicating that human Al is a widely expressed Bcl-2 homologue... - Thrombopoietin promotes beta1-integrin-mediated adhesion in hematopoietic cells via the small GTPase RaplIan S Hitchcock
Department of Medicine, University of California San Diego, La Jolla, CA, USA
Exp Hematol 35:793-801. 2007..Thrombopoietin (TPO) has previously been shown to stimulate adhesion. in certain hematopoietic cell types, although the exact mechanisms by which adhesion is promoted remain elusive... - Thrombopoietin stimulates vascular endothelial cell growth factor (VEGF) production in hematopoietic stem cellsKeita Kirito
Department of Hematology, University of Yamanashi, Yamanashi, Japan
Cell Cycle 4:1729-31. 2005.... - Thrombopoietin stimulates Hoxb4 expression: an explanation for the favorable effects of TPO on hematopoietic stem cellsKeita Kirito
Department of Medicine, Division of Hematology Oncology, University of California, San Diego, 92103, USA
Blood 102:3172-8. 2003..Together, these data provide a molecular pathway by which a growth factor can modulate a transcription factor and thereby help direct a critical developmental process... - The Mpl receptor expressed on endothelial cells does not contribute significantly to the regulation of circulating thrombopoietin levelsAmy E Geddis
Department of Pediatrics, University of California San Diego, San Diego, 92037, USA
Exp Hematol 34:82-6. 2006.... - Lineage-specific hematopoietic growth factorsKenneth Kaushansky
Department of Medicine, Division of Hematology/Oncology, University of California San Diego, San Diego, USA
N Engl J Med 354:2034-45. 2006 - Transcriptional regulation of bone marrow thrombopoietin by platelet proteinsBryan McIntosh
Department of Medicine, University of California San Diego, San Diego, CA 92103 8811, USA
Exp Hematol 36:799-806. 2008..9-kb region between 250-bp upstream of the transcriptional initiation site and the middle of the second intron are able to mediate the transcriptional repression... - Transcriptional regulation of megakaryopoiesis: thrombopoietin signaling and nuclear factorsKeita Kirito
Department of Hematology, Yamanashi Medical University, Yamansahi-Ken, Japan
Curr Opin Hematol 13:151-6. 2006..SUMMARY: The discovery that a diverse range of transcription factors are downstream effectors of thrombopoietin helps to explain the molecular mechanisms by which the hormone affects hematopoiesis... - The American Society of Hematology: a success at age 50Ernst R Jaffé
Department of Medicine, Albert Einstein College of Medicine, Bronx, NY, USA
Blood 111:11-5. 2008..The next 50 years of ASH are likely to see many profound changes, but one thing is almost certain-our dedication to fostering clinical and scientific excellence in hematology will continue as the Society's raison d'etre... - Roles of focal adhesion kinase (FAK) in megakaryopoiesis and platelet function: studies using a megakaryocyte lineage specific FAK knockoutIan S Hitchcock
Department of Medicine, University of California San Diego, La Jolla 92093, USA
Blood 111:596-604. 2008..These studies establish clear roles for FAK in megakaryocyte growth and platelet function, setting the stage for manipulation of this component of the Tpo signaling apparatus for therapeutic benefit... - Endomitotic megakaryocytes that form a bipolar spindle exhibit cleavage furrow ingression followed by furrow regressionAmy E Geddis
Department of Pediatrics, Hematology Oncology, University of California, San Diego, La Jolla, California 92093, USA
Cell Cycle 6:455-60. 2007..This finding has important implications for the potential mechanisms for cytokinesis failure in endomitosis... - Thrombopoietin enhances expression of vascular endothelial growth factor (VEGF) in primitive hematopoietic cells through induction of HIF-1alphaKeita Kirito
Department of Medicine, Division of Hematology Oncology, University of California San Diego, San Diego, CA, USA
Blood 105:4258-63. 2005..Along with previous findings that TPO affects Hox transcription factors that regulate HSC proliferation, these data contribute to our growing understanding of the mechanisms by which a hormone can influence stem cell development... - Engagement of integrin alpha4beta1 enhances thrombopoietin-induced megakaryopoiesisNorma E Fox
Department of Medicine, University of California San Diego, 92103 8811, USA
Exp Hematol 33:94-9. 2005..Moreover, a number of other hematopoietic cell types, including stem cells and erythroid progenitors, have been shown to engage and be affected by integrin ligands... - Thrombopoietin: a pan-hematopoietic cytokineAmy E Geddis
Division of Hematology, University of Washington School of Medicine, Box 357710, 1959 NE Pacific Street, Seattle, WA 98195, USA
Cytokine Growth Factor Rev 13:61-73. 2002..Our growing appreciation of how cytokine signaling pathways are translated into megakaryocyte development is discussed... - Thrombopoietin: from theory to realityKenneth Kaushansky
Department of Medicine, University of California, USA
Int J Hematol 76:343-5. 2002..The net result is the expansion of cells that give rise to mature platelets, a process that can be accentuated by the therapeutic administration of the hormone to thrombocytopenic patients... - Thrombopoietin expands hematopoietic stem cells after transplantationNorma Fox
University of California San Diego School of Medicine, Department of Medicine, San Diego, California 92103 8811, USA
J Clin Invest 110:389-94. 2002..Our results establish that TPO greatly promotes the self-renewal and expansion of HSCs in vivo following marrow transplantation... - The molecular and cellular biology of thrombopoietin: the primary regulator of platelet productionKenneth Kaushansky
Division of Hematology, University of Washington School of Medicine, 1959 NE Pacific Street, Seattle, Washington, WA 98195, USA
Oncogene 21:3359-67. 2002..This review attempts to distill what has been learned of the molecular and cellular biology of TPO and its receptor during the past several years, and links this information to several new insights into human disease and its treatment... - Identification and characterization of an isoform of murine MplDiana F Sabath
Department of Medicine, University of Washington, Harborview Medical Center, 325 Ninth Ave, Box 359756, Seattle, WA 98104, USA
Biochim Biophys Acta 1574:383-6. 2002..In summary, c-mpl-II is an isoform of murine Mpl expressed by megakaryocytes that lacks a 60 amino acid region required for surface expression of the protein... - Lineage-specific growth factors can compensate for stem and progenitor cell deficiencies at the postprogenitor cell level: an analysis of doubly TPO- and G-CSF receptor-deficient miceKenneth Kaushansky
University of Washington School of Medicine, Divisions of Hematology and Infectious Diseases, Seattle, WA 98195, USA
Blood 99:3573-8. 2002.... - Studies with chimeric Mpl/JAK2 receptors indicate that both JAK2 and the membrane-proximal domain of Mpl are required for cellular proliferationJonathan G Drachman
Puget Sound Blood Center, Seattle, Washington 98104, USA
J Biol Chem 277:23544-53. 2002..Although the nature of the signal transduction pathway is not yet known, this second proliferative event is likely to regulate c-myc expression... - JAK2, complemented by a second signal from c-kit or flt-3, triggers extensive self-renewal of primary multipotential hemopoietic cellsShengming Zhao
Division of Hematology, University of Washington, Seattle, WA, USA
EMBO J 21:2159-67. 2002..These findings suggest that a simple two-component signal can drive MHPC self-renewal... - Etiology of the myeloproliferative disorders: the role of thrombopoietinKenneth Kaushansky
Department of Medicine, University of California at San Diego Medical Center, San Diego, CA 92103, USA
Semin Hematol 40:6-9. 2003..Thus, TPO and Mpl may prove to be effective targets for both diagnosis and therapeutic management of MPD... - Inherited thrombocytopenias: toward a molecular understanding of disorders of platelet productionAmy E Geddis
Department of Pediatrics, University of California, San Diego, USA
Curr Opin Pediatr 16:15-22. 2004..To review the defined syndromes of inherited thrombocytopenia and discuss new genetic data for several disorders that shed light on the process of megakaryopoiesis... - Megakaryocytes require thrombospondin-2 for normal platelet formation and functionThemis R Kyriakides
Department of Biochemistry, University of Washington, Seattle, WA 98195, USA
Blood 101:3915-23. 2003..We conclude that the uptake of TSP2 by MKs from the marrow milieu is required for proper MK function and the release of functionally competent platelets... - Cross-reactivity between erythropoietin and thrombopoietin at the level of Mpl does not account for the thrombocytosis seen in iron deficiencyAmy E Geddis
J Pediatr Hematol Oncol 25:919-20; author reply 920. 2003 - Thrombopoietin induces HOXA9 nuclear transport in immature hematopoietic cells: potential mechanism by which the hormone favorably affects hematopoietic stem cellsKeita Kirito
Department of Medicine, University of California San Diego School of Medicine, 402 Dickinson St, Suite 380, San Diego, CA 92103 8811, USA
Mol Cell Biol 24:6751-62. 2004..Our data suggest that TPO controls HSC development through the regulation of multiple members of the Hox family of transcription factors through multiple mechanisms... - Megakaryocytes express functional Aurora-B kinase in endomitosisAmy E Geddis
Division of Pediatric Hematology Oncology, University of California San Diego UCSD, 9500 Gilman Dr, Mailcode 0665, La Jolla, CA 92093, USA
Blood 104:1017-24. 2004..These results suggest that EnM MKs appropriately express functional Aurora-B kinase and related proteins in early anaphase, making a simple deficiency of this protein an unlikely explanation for polyploidy in this cell type... - On the molecular origins of the chronic myeloproliferative disorders: it all makes senseKenneth Kaushansky
Department of Medicine, Division of Hematology/Oncology, University of California San Diego, 402 Dickinson St, Ste 380, San Diego, CA 92103-8811, USA
Blood 105:4187-90. 2005 - PI3K/Akt/FOXO3a pathway contributes to thrombopoietin-induced proliferation of primary megakaryocytes in vitro and in vivo via modulation of p27(Kip1)Takafumi Nakao
Department of Medicine, Division of Hematology Oncology, University of California San Diego, La Jolla, California, USA
Cell Cycle 7:257-66. 2008.... - A novel RUNX1 mutation in familial platelet disorder with propensity to develop myeloid malignanciesKeita Kirito
Haematologica 93:155-6. 2008..Among the three affected individuals, two members developed myeloid malignancies. Sequence studies demonstrate that all affected individuals of the pedigree display a heterozygous single nucleotide deletion in exon 8 of the RUNX1 gene... - Thrombocytosis in an infant with high thrombopoietin concentrationsJane Hankins
Department of Hematology-Oncology, St Jude Children's Research Hospital, Memphis, Tennessee 38105, USA
J Pediatr Hematol Oncol 26:142-5. 2004..This case may represent a case of atypical ET in which thrombocytosis results from TPO stimulation rather than clonal proliferation. Measuring TPO concentrations may be warranted for children with unexplained extreme thrombocytosis... - Cytoprotective doses of erythropoietin or carbamylated erythropoietin have markedly different procoagulant and vasoactive activitiesThomas R Coleman
The Kenneth S Warren Institute, Warren Pharmaceuticals, Ossining, NY 10562, USA
Proc Natl Acad Sci U S A 103:5965-70. 2006..These preclinical findings suggest that nonerythropoietic tissue-protective ligands, which appear to elicit fewer adverse effects, may be especially useful in clinical settings for tissue protection... - The common gamma chain (gamma c) is a required signaling component of the IL-21 receptor and supports IL-21-induced cell proliferation via JAK3Tania Habib
Division of Hematology, University of Washington School of Medicine, Seattle, Washington 98195, USA
Biochemistry 41:8725-31. 2002.... - The glycan domain of thrombopoietin (TPO) acts in trans to enhance secretion of the hormone and other cytokinesHannah M Linden
Division of Hematology, University of Washington School of Medicine, Seattle, Washington 98195, USA
J Biol Chem 277:35240-7. 2002..The cellular location of TGD action is likely to be within the ER or earlier in the secretory pathway... - Physician-scientists: preparation, opportunities, and national needKenneth Kaushansky
Department of Medicine, University of California San Diego, University of California San Diego Medical Center, San Diego, California 92103-8811, USA
Exp Biol Med (Maywood) 228:1258-60. 2003 - Blocking the alpha 4 integrin-paxillin interaction selectively impairs mononuclear leukocyte recruitment to an inflammatory siteChloe C Feral
Department of Medicine, University of California San Diego, La Jolla, California 92093 0726, USA
J Clin Invest 116:715-23. 2006..We conclude that interference with alpha4 integrin signaling can selectively impair mononuclear leukocyte recruitment to sites of inflammation while sparing vital functions of alpha4 integrins in development and hematopoiesis... - Celebrate hematologyKenneth Kaushansky
Blood 100:4257-8. 2002 - Hematopoietic growth factors, signaling and the chronic myeloproliferative disordersKenneth Kaushansky
Department of Medicine, Division of Hematology/Oncology, University of California, 402 Dickinson Street, Suite 380, San Diego, CA 92103-8811, USA
Cytokine Growth Factor Rev 17:423-30. 2006....
Research Grants
- MOLECULAR AND CELLULAR BIOLOGY OF THROMBOPOIETINKenneth Kaushansky; Fiscal Year: 2002..Together, the proposed work should advance our understanding of hematopoietic regulation, potentially providing new opportunities to rationally intervene to stimulate normal or suppress neoplastic blood cell production. ..
- Cell biology of megakaryocytes and platelets 2005Kenneth Kaushansky; Fiscal Year: 2005..This application is a request for partial funds to support the attendance of speakers and discussion leaders, and selected postdoctoral fellows and students at this important new meeting. ..
- GROWTH FACTORS IN NORMAL AND NEOPLASTIC HEMATOPOIESISKenneth Kaushansky; Fiscal Year: 2006....
- MOLECULAR AND CELLULAR BIOLOGY OF THROMBOPOIETINKenneth Kaushansky; Fiscal Year: 2007..It is hoped that the successful completion of these studies will further our understanding of hematopoiesis. ..
- 2007 Cell Biology of Megakaryocytes and Platelets GRCKenneth Kaushansky; Fiscal Year: 2007..This application is a request for partial funds to support the attendance of participants (i.e. speakers, discussion leaders, postdoctoral fellows, students, etc.) at this important scientific meeting. ..
- GROWTH FACTORS IN NORMAL AND NEOPLASTIC HEMATOPOIESISKenneth Kaushansky; Fiscal Year: 2001....
- GROWTH FACTORS IN NORMAL AND NEOPLASTIC HEMATOPOIESISKenneth Kaushansky; Fiscal Year: 1991..The strategy will involve subtraction hybridization to enrich mRNA for the growth factor, generation of a cDNA library in an expression vector, and identification of useful clones by biological assays...
- GROWTH FACTORS IN NORMAL AND NEOPLASTIC HEMATOPOIESISKenneth Kaushansky; Fiscal Year: 1993....
- MOLECULAR AND CELLULAR BIOLOGY OF THROMBOPOIETINKENNETH contact KAUSHANSKY; Fiscal Year: 2010..The results of these studies will provide new insights into the role of thrombopoietin signaling in normal as well as malignant cells. ..