Faculty Profile

Kenneth Kaushansky, M.D., M.A.C.P.

Kenneth Kaushansky, M.D., M.A.C.P.

Helen M. Ranney Distinguished Professor

Chair, Department of Medicine

Office Address:

9500 Gilman Drive # 0671

La Jolla, CA 92093-0671

kkaushansky@ucsd.edu
Office: 858-822-3345
Fax:    858-822-3344

 
 

Education and Training

B.S. University of California at Los Angeles 1975
M.D. University of California at Los Angeles 1979

Internship

 University of Washington 1979 - 1980
Residency University of Washington 1980 - 1982
Chief Resident University of Washington 1982
Fellowship University of Washington 1982 - 1986

 

Biography

Kenneth Kaushansky, M.D., M.A.C.P. earned his B.S. and M.D. degrees from the University of California, Los Angeles, and completed his Internal Medicine Internship, Residency and Chief Medical Residency, and Fellowship in Hematology at the University of Washington.  He joined the faculty at the University of Washington as an Assistant Professor in 1987, was promoted to Associate Professor in 1991 and to Professor in 1995. Following his service as Hematology Section Chief at the University of Washington Medical Center, Dr. Kaushansky was named Helen M. Ranney Professor and Chair of the Department of Medicine at UC San Diego in February 2002.

During his career Dr. Kaushansky has been a successful teacher, clinician and biomedical researcher. His laboratory work has lead to several significant discoveries, for which he received the Dameshek Award from the American Society of Hematology, awarded annually to the scientist who has provided the most seminal insight into the Pathophysiology of hematological disorders, and the Outstanding Investigator Award from the American Society for Medical Research, the most prestigious award of the Society. Dr. Kaushansky is a past-president of the American Society for Clinical Investigation (2004 – 2005) and the Western Society for Clinical Investigation (1998 – 1999) and is the Past President of the American Society of Hematology (ASH). He also served a 5 year term as Editor-in-Chief of the journal Blood (1998-2002) and as a major reviewer for the NIH and many major scientific periodicals. Dr. Kaushansky has been recognized for his scientific and clinical contributions by election as a Master of the American College of Physicians, and to several honor societies and organizations, including the American Society for Clinical Investigation, the Association of American Physicians, the Institute of Medicine of the National Academies of Science and the American Academy of Arts and Sciences.

Dr. Kaushansky is a leading hematologist who has conducted seminal research on the molecular biology of blood cell production. His team has cloned several of the genes important in the growth and differentiation of blood cells, including thrombopoietin, a key regulator of stem cell and platelet production. He is an accomplished clinician, and he has been a champion of the need to train more physician-scientists who can bridge the gap between the laboratory and the clinical arena, translating research discoveries into improved treatments and technologies for the prevention, diagnosis and management of disease.

 

 

Publications

  1. Kaushansky K, Lok S, Holly RD, et al.:  Promotion of megakaryocyte progenitor expansion and differentiation by the c-Mpl ligand thrombopoietin.  Nature 1994;369:568-571.

  2. Lok S, Kaushansky K, Holly RD, et al.:  Cloning and expression of murine thrombopoietin cDNA and stimulation of platelet production in vivo.  Nature 1994;369:565-568.

  3. Kaushansky K:  Thrombopoietin:  The primary regulator of platelet production.  Blood 1995;86:419-431.

  4. Kaushansky K, Broudy VC, Lin N, Jorgensen MJ, McCarty J, Fox N, Zucker-Franklin D, Lofton-Day C:  Thrombopoietin, the Mpl-ligand, is essential for full megakaryocyte development.  Proc Natl Acad Sci USA 1995; 92:3234-3238.

  5. Drachman J, Griffin JD, Kaushansky K:  Stimulation of tyrosine kinase activity by MPL-ligand (thrombopoietin).  J Biol Chem 1995;270:4979-4982.

  6. Broudy VC, Lin NL, Kaushansky K:  Thrombopoietin acts synergistically with erythropoietin, stem cell factor, and IL-11 to enhance murine megakaryocyte colony growth and increases megakaryocyte ploidy in vitro.  Blood 1995; 85:1719-1726.

  7. Kaushansky K, Broudy VC, Lin N, Jorgensen MJ, McCarty J, Fox N, Zucker-Franklin D, Lofton-Day C:  Thrombopoietin, the Mpl-ligand, is essential for full megakaryocyte development.  Proc Natl Acad Sci USA 1995; 92:3234-3238. 

  8. Broudy VC, Lin NL, Kaushansky K:  Thrombopoietin acts synergistically with erythropoietin, stem cell factor, and IL-11 to enhance murine megakaryocyte colony growth and increases megakaryocyte ploidy in vitro.  Blood 1995; 85:1719-1726.

  9. Kaushansky K, Broudy VC, Lin N, Jorgensen MJ, McCarty J, Fox N, Zucker-Franklin D, Lofton-Day C:  Thrombopoietin, the Mpl-ligand, is essential for full megakaryocyte development.  Proc Natl Acad Sci USA 1995; 92:3234-3238.

  10. Kaushansky K, Broudy VC, Grossmann A Humes J, Lin N, Ren H-P, Bailey MC, Papayannopoulou T, Forstrom JW, Sprugel KH:  Thrombopoietin expands erythroid progenitors, increases red cell production, and enhances erythroid recovery after myelosuppressive therapy.  J Clin Invest 1995; 96:1683-1687.

  11. McCarty JM, Sprugel KH, Fox NE, Sabath DE, Kaushansky K:  Murine thrombopoietin mRNA levels are modulated by platelet count.  Blood 1995; 86:3668-3675.

  12. Papayannopoulou Th, Brice M, Farrer D, Kaushansky K:. Insights into the cellular mechanisms of erythropoietin-thrombopoietin synergy.  Exp Hematol 1996; 24:660-669.

  13. Sitnicka E, Lin N, Priestley GV, Fox, N, Broudy VC, Wolf NS, Kaushansky K:  The effect of thrombopoietin on the proliferation and differentiation of murine hematopoietic stem cells.  Blood 1996; 87:4998-5005.

  14. Fero ML, Rivkin M, Tasch M, Porter P, Carow CE, Firpo E, Polyak K, Tsai LH, Broudy VC, Perlmutter R, Kaushansky K, Roberts JM: A syndrome of gigantism, tumorigenesis and female sterility in p27Kip-1 deficient mice. Cell 1996; 85:733-744.

  15. Zucker-Franklin D, Kaushansky K: The effect of Thrombopoietin on the development of megakaryocytes and platelets: An ultrastructural analysis. Blood 1996; 88:1632-1638.

  16. Broudy VC, Lin NL, Fox N, Taga T, Kaushansky K:  Thrombopoietin stimulates CFU-Meg proliferation and megakaryocyte maturation independently of cytokines that signal through the gp130 receptor subunit. Blood 1996; 88: 2026-2032.

  17. Drachman JD, Sabath DF, Fox, NE, Kaushansky K: Thrombopoietin (TPO) induces  tyrosine phosphorylation of JAK2, TYK 2, STAT 3 and STAT 5b in megakaryocytes. Blood 1997; 89:483-492.

  18. Broudy VC, Lin NL, Sabath DF, Papayannopoulou Th, Kaushansky K: Human platelets display high affinity receptors for thrombopoietin. Blood 1997; 89:1896-1904.

  19. Drachman JG, Kaushansky K: Dissecting the thrombopoietin receptor: Functional elements of the mpl cytoplasmic domain. Proc Natl Acad Sci USA 1997; 94:2350-2355.

  20. Kaushansky K: Thrombopoietin. Drug Therapy Series. New Engl J Med. 1998; 339:746-754.

  21. Drachman JG, Millett KM, Kaushansky K: Mpl signal transduction requires functional JAK2, not TYK2. J Biol Chem 1999; 274:13480-13484.

  22. Rojnuckarin P, Drachman JG, Kaushansky K: Thrombopoietin-induced activation of the mitogen activated protein kinase pathway in normal megakaryocytes: Role in endomitosis. Blood 1999; 94:1273-1282.

  23. Hodohara K, Fujii N, Yamamoto N, Kaushansky K: Stromal cell derived factor 1 acts synergistically with thrombopoietin to enhance the development of megakaryocytic progenitor cells. Blood 2000; 95:769-775.

  24. Wang Q, Fox N, Kaushansky K: Interferon-a directly represses megakaryopoiesis by inhibiting TPO-induced signaling through induction of SOCS-1. Blood 2000; 96:2093-2099.

  25. Miyakawa Y, Drachman JG, Gallis B, Kaushansky A, Kaushansky K: A Structure-function analysis of serine/threonine phosphorylation of the thrombopoietin receptor, c-MPL. J Biol Chem 2000; 275:32214-32219.

  26. Parrish-Novak J, Dillon SR, Nelson A, Hammond A, Sprecher C, Gross JA, Johnston J, Madden K, Xu W, West J, Schrader S, Burkhead S, Heipel M, Brandt C, Kuijper J, Kramer J, Conklin D, Presnell SR, Berry J, Shiota F, Bort S, Hambly K†, Mudri S, Clegg C, Moore M, Grant FJ, Lofton-Day C, Gilbert T, Raymond F, Ching A, Yao L, Smith D, Webster P, Whitmore T, Maurer M, Kaushansky K, Holly R, Foster D. Interleukin 21 and IL21R: A novel cytokine-receptor pair involved in NK cell expansion and lymphocyte function. Nature 2000; 408: 57-63.

  27. Rojnuckarin P, Kaushansky K: Megakaryocyte proplatelet formation is dependent on PKCa. Blood 2001; 97:154-161.

  28. Miyakawa Y, Rojnuckarin P, Habib T, Kaushansky K: Thrombopoietin induces PI3K and SHP2 activation through Gab and IRS proteins in BaF3 cells and primary murine megakaryocytes. J Biol Chem 2001; 276:2494-2502.

  29. Carow CE, Fox N, Kaushansky K: The Kinetics of Endomitosis in Primary Murine Megakaryocytes. J Cell Physiol 2001; 188:291-303.

  30. Geddis A, Fox N, Kaushansky K: Phosphatidylinositol 3-kinase (PI3K) is necessary but not sufficient for thrombopoietin-induced proliferation in engineered Mpl-bearing cell lines as well as in primary megakaryocytic progenitors. J Biol Chem 2001; 276: 34473-34479.

  31. Rojnuckarin P, Miyakawa Y, Fox NE, Deou J, Daum G, Kaushansky K: The roles of PI3K and PKCz for thrombopoietin-induced MAP kinase activation in primary murine megakaryocytes. J Biol Chem 2001; 276: 41014-41022.

  32. Linden HM, Kaushansky K: The glycan domain of thrombopoietin (TPO) acts in trans to enhance secretion of the hormone and other cytokines. J Biol Chem 2002; 277:35240-35247.

  33. Drachman JD, Miyakawa Y, Luthi J, Dahlen DD, Raney A, Geddis AE, Kaushansky K: Mpl/JAK  chimeric receptors: both Jak2 and the membrane proximal domain of Mpl are required for proliferation. J Biol Chem 2002; 277: 23544-23553.

  34. Habib T, Weinberg K, Kaushansky K. The common g chain (gC) is a required signaling component of the IL-21 receptor and supports IL-21-induced cell proliferation via JAK3. Biochemistry 2002; 41:8725-8731.

  35. Kaushansky K, Fox NE, Lin NL, Liles WC: Lineage-specific growth factors can compensate for stem and progenitor cell deficiencies at the post-progenitor cell level: An analysis of doubly TPO- and G-CSF receptor-deficient mice. Blood 2002; 99: 3573-3578.

  36. Fox NE, Priestley GV, Papayannopoulou Th, Kaushansky K: Thrombopoietin (TPO) Expands Hematopoietic Stem Cells (HSCs) in vivo. J Clin Invest 2002;110: 389-394.

  37. Habib T, Nelson A, Kaushansky K. Interleukin 21 activates JAK1 and JAK3 and induces a distinct profile of STAT phosphorylation. J Clin Allergy Immunol 2003;112:1033-1045.

  38. Kirito K, Fox NE, Kaushansky K: Thrombopoietin stimulates expression of HoxB4: An explanation for the favorable effects of  TPO on hematopoietic stem cells. Blood 2003;102:3172-3178.

  39. Geddis AE, Kaushansky K.  Megakaryocytes express functional aurora kinase B in endomitosis. Blood 2004; 104:1017-1024.

  40. Kirito K, Fox NE, Kaushansky K. Thrombopoietin (TPO) induces the nuclear translocation of HoxA9 in hematopoietic stem cells  (HSC): A potential explanation for the favorable effects of TPO on HSCs.  Mol Cell Bio 2004;24:6751-62.

  41. Fox NE, Kaushansky K: Engagement of integrin a4b1 enhances thrombopoietin induced megakaryopoiesis. Exp Hematol. 2005;33:94-99.

  42. Kirito K, Fox NE, Kaushansky K: Thrombopoietin enhances expression of vascular endothelial cell growth factor (VEGF) in primitive hematopoietic cells through induction of HIF-1a. Blood 2005; 105:4258-4263.

  43. Chanprasert S, Geddis AE, Barroga C, Fox NE, Kaushansky K. Thrombopoietin (TPO) induces c-myc expression through a PI3K- and MAPK-dependent pathway that is not mediated by Akt, PKCζ or mTOR in TPO-dependent cell lines and primary megakaryocytes. Cell Signaling, 2005; 18:1212-1218

  44. Kaushansky K. The molecular mechanisms that control thrombopoiesis. J. Clin Invest. 2005; 115:3339-3347.

  45. Geddis AE, Fox NE, Kaushansky K: The Mpl receptor expressed on endothelial cells does not contribute significantly to the regulation of circulating thrombopoietin (TPO) levels. Exp Hematol. 2006; 34:82-86.

  46. Geddis AE, Kaushansky K. Endomitotic megakaryocytes form a midzone in anaphase but have a deficiency in cleavage furrow formation. Cell Cycle. 2006; 5:538-545.

  47. Kaushansky K. Lineage specific hematopoietic growth factors. New Engl. J Med. 2006;354:2034-2045.

  48. Geddis AE, Fox NE, Tkachenko E, Kaushansky K. Low ploidy endomitotic megakaryocytes exhibit cleavage furrow regression following furrow ingression. Cell Cycle. 6:455-460, 2007

  49. Hitchcock IS, Kaushansky K. Thrombopoietin promotes b1 integrin-mediated adhesion in hematopoietic cells via the small GTPase Rap1. Exp Hematology, 2007;35:793-801

  50. Hitchcock I, Fox NE, Prevost N, Sear K, Kaushansky K. Roles of Focal Adhesion Kinase (FAK) in megakaryopoiesis and platelet function: Studies using a megakaryocyte lineage-specific FAK knockout. Blood, 111:596-604, 2008

  51. Nakao T, Geddis AE, Fox NE, Kaushansky K. PI3K/Akt/FOXO3a pathway contributes to thrombopoietin-induced proliferation of primary megakaryocytes in vitro and in vivo via modulation of p27Kip1 Cell Cycle, 7:257-266, 2008

  52. McIntosh B, Kaushansky K: Marrow stromal production of thrombopoietin is regulated by transcriptional mechanisms in response to platelet products. Exp. Hematol. 2008, April 12. In Press

  53. Hitchcock I, Chen M, Fox NE, Kaushansky K. YRRL motifs in the cytoplasmic domain of the thrombopoietin receptor regulate receptor internalization and degradation. Blood, 2008; 112:2222-2231

  54. Barroga C, Pham H, Kaushansky K. Thrombopoietin regulates c-myb expression by modulating microRNA (miR)150 expression. Exp Hematol. 2008;36:1585-1592

  55. Soda M, Willert K, Kaushansky K, Geddis A. Inhibition of GSK-3a promotes survival and proliferation of megakaryocytic cells through b-catenin-independent signaling. Cell Signal. 2008 20:2317-2323