Kenneth Dorshkind, Ph.D.

Laboratory Address:
Factor 11-640

Work Address:
A2-179 CHS
CAMPUS - 173216
CA Factor
Los Angeles, CA 90095

Affiliations
Affiliations
Vice-Chair, Research and Professor, Pathology and Laboratory Medicine
Member, Eli & Edythe Broad Center of Regenerative Medicine & Stem Cell Research, JCCC Cancer and Stem Cell Biology Program Area, Molecular, Cellular & Integrative Physiology GPB Home Area
Research Interests
The overall goal of the laboratory is to study B cell development during fetal and adult life. The first B lineage cells emerge in the embryo, and recent studies have demonstrated that these arise from a B lineage progenitor whose developmental potential is restricted to the production of B-1 B cells. B-1 B cells are a minor population of B lymphocytes that are involved in innate immune responses. B cell progenitors that derive from hematopoietic stem cells, and which are destined to produce B-2 B cells, arise subsequently during embryogenesis. B-2 B cells comprise the majority of B cells in the peripheral lymphoid organs and take part in adaptive immune responses. The production of B-2 B cells occurs in the bone marrow throughout life. One aim of the laboratory is to characterize the fetal wave of B cell development in which B-1 B cell progenitors are generated. Emerging data indicate that the transcriptional and microenvironmental regulation of B-1 B cell development is distinct from B-2 B cell differentiation, and a major goal is to compare and contrast these two waves of B lymphopoiesis. Additional work in the laboratory has demonstrated that B-2 B cell development in the bone marrow is reduced with age, and ongoing studies are aimed at defining the microenvironmental and cell intrinsic events that underlie this decline.
Biography

B and T Cell Development The development of B and T lymphocytes occurs in the bone marrow and thymus, respectively, in association with a supporting framework of stromal cells. One aim of our work is to characterize immature lymphoid progeny derived from pluripotential hematopoietic stem cells. A current focus of the laboratory is on the characterization of a B/macrophage progenitor that has recently been identified in adult bone marrow. The origin of these cells and the contribution of their progeny to the adult immune system is being assessed. Another major aim of the laboratory is to define the basis for thymic involution during aging and to develop protocols for rejuvenation of that organ. Multiple in vitro and in vivo systems have been developed to facilitate these studies. Students who enter the laboratory receive state of the art training in such techniques as cell culture, flow cytometry, and bone marrow transplantation. This background provides then the skills necessary to address issues in Hematopoiesis and Developmental Immunology.

Publications
Montecino-Rodriguez Encarnacion, Berent-Maoz Beata, Dorshkind Kenneth Causes, consequences, and reversal of immune system aging. The Journal of clinical investigation. 2013; 123(3): 958-65.
E. Montecino-Rodriguez and K. Dorshkind B-1 B cell development in the fetus and adult. Immunity 2012; 36: 13-21.
Montecino-Rodriguez Encarnacion, Dorshkind Kenneth B-1 B cell development in the fetus and adult. Immunity. 2012; 36(1): 13-21.
B. Berent-Maoz, E. Montecino-Rodriguez, and K. Dorshkind Fibroblast growth factor-7 partially reverses thymocyte progenitor aging by repression of Ink4a. Blood 2012; 119: 5715-5721.
Berent-Maoz Beata, Montecino-Rodriguez Encarnacion, Dorshkind Kenneth Genetic regulation of thymocyte progenitor aging. Seminars in immunology. 2012; 24(5): 303-8.
Barber Chad L, Montecino-Rodriguez Encarnacion, Dorshkind Kenneth Developmental relationships between B-1 and B-2 progenitors. Cell cycle (Georgetown, Tex.). 2011; 10(22): 3810-1.
Montecino-Rodriguez, E. and K. Dorshkind Formation of B-1 B Cells from Neonatal B-1 Transitional Cells Exhibits NF-kB Redundancy. J. Immunol 2011; PMID 22031760: .
Montecino-Rodriguez Encarnacion, Dorshkind Kenneth Formation of B-1 B cells from neonatal B-1 transitional cells exhibits NF-κB redundancy. Journal of immunology (Baltimore, Md. : 1950). 2011; 187(11): 5712-9.
Barber, C.L., E. Montecino-Rodriguez, and K. Dorshkind Reduced production of B-1-specified common lymphoid progenitors results in diminished potential of adult marrow to generate B-1 cells. . Proc. Natl. Acad. Sci. USA 2011; 108: 13700-13704.
Barber Chad L, Montecino-Rodriguez Encarnacion, Dorshkind Kenneth Reduced production of B-1-specified common lymphoid progenitors results in diminished potential of adult marrow to generate B-1 cells. Proceedings of the National Academy of Sciences of the United States of America. 2011; 108(33): 13700-4.
Signer Robert A J, Montecino-Rodriguez Encarnacion, Witte Owen N, Dorshkind Kenneth Immature B-cell progenitors survive oncogenic stress and efficiently initiate Ph+ B-acute lymphoblastic leukemia. Blood. 2010; 116(14): 2522-30.
Dorshkind Kenneth Not a split decision for human hematopoiesis. Nature immunology. 2010; 11(7): 569-70.
Dorshkind Kenneth, Swain Susan Age-associated declines in immune system development and function: causes, consequences, and reversal. Current opinion in immunology. 2009; 21(4): 404-7.
Signer, R.A., E. Montecino-Rodriguez, O.N. Witte, and K. Dorshkind Immature B-cell progenitors survive oncogenic stress and efficiently initiate Ph+ B-acute lymphoblastic leukemia. Blood 2009; 116: 2522-2530.
Dorshkind, K., Montecino-Rodriguez, E., and Signer, R.A.J. The ageing immune system: is it ever too old to become young again?. Nature Reviews Immunol 2009; 9: 57-62.
Dorshkind Kenneth, Montecino-Rodriguez Encarnacion, Signer Robert A J The ageing immune system: is it ever too old to become young again?. Nature reviews. Immunology. 2009; 9(1): 57-62.
Signer, R.A.J., Montecino-Rodriguez, E., Witte, O.N., and Dorshkind, K. Aging and cancer resistance in lymphoid progenitors are linked processes conferred by p16Ink4a and Arf. Genes & Development 2008; 22: 3115-3220.
Signer Robert A J, Montecino-Rodriguez Encarnacion, Witte Owen N, Dorshkind Kenneth Aging and cancer resistance in lymphoid progenitors are linked processes conferred by p16Ink4a and Arf. Genes & development. 2008; 22(22): 3115-20.
Signer, R.A.J., Montecino-Rodriguez, E., Witte, O.N., McLaughlin, J, Dorshkind, K. Age-related defects in B lymphopoiesis underlie the myeloid dominance of adult leukemia. Blood 2007; 110: 1831-1839.
Signer Robert A J, Montecino-Rodriguez Encarnacion, Witte Owen N, McLaughlin Jami, Dorshkind Kenneth Age-related defects in B lymphopoiesis underlie the myeloid dominance of adult leukemia. Blood. 2007; 110(6): 1831-9.
Monroe, J.G., Dorshkind, K. Fate decisions regulating bone marrow and peripheral B lymphoid development. Adv. Immunol 2007; 95: 1-50.
Monroe John G, Dorshkind Kenneth Fate decisions regulating bone marrow and peripheral B lymphocyte development. Advances in immunology. 2007; 95(3): 1-50.
Dorshkind, K. Montecino-Rodriguez, E. Fetal B-cell lymphopoiesis and the emergence of B-1-cell potential. Nature Rev. Immunol 2007; 7: 213-219.
Dorshkind Kenneth, Montecino-Rodriguez Encarnacion Fetal B-cell lymphopoiesis and the emergence of B-1-cell potential. Nature reviews. Immunology. 2007; 7(3): 213-9.
Dorshkind Kenneth, Witte Owen N Linking the hematopoietic microenvironment to imatinib-resistant Ph+ B-ALL. Genes & development. 2007; 21(18): 2249-52.
Hardy, R.R., Kincade, P.W., Dorshkind, K. The protean nature of B lineage cells. Immunity 2007; 26: 703-714.
Hardy Richard R, Kincade Paul W, Dorshkind Kenneth The protean nature of cells in the B lymphocyte lineage. Immunity. 2007; 26(6): 703-14.
Min Hyeyoung, Montecino-Rodriguez Encarnacion, Dorshkind Kenneth Effects of aging on the common lymphoid progenitor to pro-B cell transition. Journal of immunology (Baltimore, Md. : 1950). 2006; 176(2): 1007-12.
Montecino-Rodriguez, E., Dorshkind, K. Evolving patterns of lymphopoiesis from embryogenesis through senescence. Immunity 2006; 24: 659-662.
Montecino-Rodriguez Encarnacion, Dorshkind Kenneth Evolving patterns of lymphopoiesis from embryogenesis through senescence. Immunity. 2006; 24(6): 659-62.
Smale Stephen T, Dorshkind Kenneth Hematopoiesis flies high with Ikaros. Nature immunology. 2006; 7(4): 367-9.
Montecino-Rodriguez E, Leathers H, Dorshkind K Identification of a B-1 B cell-specified progenitor. Nature Immunology 2006; 7: 293-301.
Montecino-Rodriguez Encarnacion, Leathers Hyosuk, Dorshkind Kenneth Identification of a B-1 B cell-specified progenitor. Nature immunology. 2006; 7(3): 293-301.
Montecino-Rodriguez Encarnacion, Dorshkind Kenneth New perspectives in B-1 B cell development and function. Trends in immunology. 2006; 27(9): 428-33.
Min Hyeyoung, Montecino-Rodriguez Encarnacion, Dorshkind Kenneth Reassessing the role of growth hormone and sex steroids in thymic involution. Clinical immunology (Orlando, Fla.). 2006; 118(1): 117-23.
Montecino-Rodriguez, E. Dorshkind, K. Stromal cell-dependent growth of B-1 B cell progenitors in the absence of direct contact. Nature Protocols 2006; 3: 1140-1144.
Montecino-Rodriguez Encarnacion, Dorshkind Kenneth Stromal cell-dependent growth of B-1 B cell progenitors in the absence of direct contact. Nature protocols. 2006; 1(3): 1140-4.
Min Hyeyoung, Montecino-Rodriguez Encarnacion, Dorshkind Kenneth Effects of aging on early B- and T-cell development. Immunological reviews. 2005; 205(6): 7-17.
Montecino-Rodriquez Encarnacion, Min Hyeyoung, Dorshkind Kenneth Reevaluating current models of thymic involution. Seminars in immunology. 2005; 17(5): 356-61.
Dovat Sinisa, Montecino-Rodriguez Encarnacion, Schuman Valerie, Teitell Michael A, Dorshkind Kenneth, Smale Stephen T Transgenic expression of Helios in B lineage cells alters B cell properties and promotes lymphomagenesis. Journal of immunology (Baltimore, Md. : 1950). 2005; 175(6): 3508-15.
Linton Phyllis Jean, Dorshkind Kenneth Age-related changes in lymphocyte development and function. Nature immunology. 2004; 5(2): 133-9.
Dorshkind Kenneth, Witte Owen Got MLL? Definitive hematopoiesis requires MLL gene expression. Molecular cell. 2004; 13(6): 765-6.
Dogusan Zeynep, Montecino-Rodriguez Encarnacion, Dorshkind Kenneth Macrophages and stromal cells phagocytose apoptotic bone marrow-derived B lineage cells. Journal of immunology (Baltimore, Md. : 1950). 2004; 172(8): 4717-23.
Min Hyeyoung, Montecino-Rodriguez Encarnacion, Dorshkind Kenneth Reduction in the developmental potential of intrathymic T cell progenitors with age. Journal of immunology (Baltimore, Md. : 1950). 2004; 173(1): 245-50.
Dorshkind Kenneth, Welniak Lisbeth, Gault Ruth A, Hixon Julie, Montecino-Rodriguez Encarnacion, Horseman Nelson D, Gertner Joseph M, Murphy William J Effects of housing on the thymic deficiency in dwarf mice and its reversal by growth hormone administration. Clinical immunology (Orlando, Fla.). 2003; 109(2): 197-202.
Montecino-Rodriguez Encarnacion, Dorshkind Kenneth To T or not to T: reassessing the common lymphoid progenitor. Nature immunology. 2003; 4(2): 100-1.
Lian Zhe-Xiong, Okada Tomoyuki, Kita Hiroto, Hsu Tom, Shultz Leonard D, Dorshkind Kenneth, Ansari Aftab A, Naiki Mitsuru, Ikehara Susumu, Gershwin M Eric Age-related alterations in the lymphohematopoietic and B-lineage precursor populations in NZB mice. Stem cells (Dayton, Ohio). 2002; 20(4): 293-300.
Hashimoto Yoshiko, Montecino-Rodriguez Encarnacion, Leathers Hyosuk, Stephan Robert P, Dorshkind Kenneth B-cell development in the thymus is limited by inhibitory signals from the thymic microenvironment. Blood. 2002; 100(10): 3504-11.
Montecino-Rodriguez Encarnacion, Dorshkind Kenneth Identification of B/macrophage progenitors in adult bone marrow. Seminars in immunology. 2002; 14(6): 371-6.
Hashimoto Yoshiko, Montecino-Rodriguez Encarnacion, Gershwin M Eric, Dorshkind Kenneth Impaired development of T lymphoid precursors from pluripotent hematopoietic stem cells in New Zealand Black mice. Journal of immunology (Baltimore, Md. : 1950). 2002; 168(1): 81-6.
Lian Zhe-Xiong, Kita Hiroto, Okada Tomoyuki, Hsu Tom, Shultz Leonard D, Dorshkind Kenneth, Ansari Aftab A, Ikehara Susumu, Naiki Mitsuru, Gershwin M Eric Increased frequency of pre-pro B cells in the bone marrow of New Zealand Black (NZB) mice: implications for a developmental block in B cell differentiation. Developmental immunology. 2002; 9(1): 35-45.
Dorshkind Kenneth Multilineage development from adult bone marrow cells. Nature immunology. 2002; 3(4): 311-3.
Paquette Ronald, Dorshkind Kenneth Optimizing hematopoietic recovery following bone marrow transplantation. The Journal of clinical investigation. 2002; 109(12): 1527-8.
Dorshkind Kenneth Stem cells and lineage plasticity: the challenge to existing paradigms. Immunological reviews. 2002; 187(10): 5-8.