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

A selected list of 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.