All blood cells, including B- and T-lymphocytes, are derived from a common precursor known as the hematopoietic stem cell. B- and T-cells are the principal cells involved in the production of antibodies and in the defense against viruses and tumors. If the number of mature B- and T-cells produced is not normal, individuals may be more prone to infection and disease. At the other end of the spectrum, overproduction of B- and T-cells and/or their precursors may occur in various forms of leukemia. The aim of Dr. Kenneth Dorshkind's laboratory is to study how B- and T-cells normally develop in order to have a basis for understanding defects in their production.
B- and T-lymphocytes are produced in the bone marrow and thymus, respectively, and are the principal effectors of immunity. One aim of Dorshkind's work is to characterize immature lymphoid progeny derived from the pluripotential hematopoietic stem cell during fetal and adult life. He and his colleagues are particularly interested in defining branch points at which precursors lose their multipotentiality and become committed to generating either B- or T-cells. Another aim of the Dorshkind laboratory is to identify age-related changes in the hematopoietic system and determine how they may contribute to abnormal blood cell development and function.
Selected Cancer-Related Publications:
Montecino-Rodriguez E, Dorshkind K. B-1 B cell development in the fetus and adult. Immunity. 2012 Jan 27;36(1):13-21.
Barber CL, Montecino-Rodriguez E, Dorshkind K. 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 U S A. 2011 Aug 16;108(33):13700-4. Epub 2011 Aug 1
Signer RA, Montecino-Rodriguez E, Witte ON, Dorshkind K. Immature B-cell progenitors survive oncogenic stress and efficiently initiate Ph+ B-acute lymphoblastic leukemia. Blood. 2010 Oct 7;116(14):2522-30. Epub 2010 Jun 18
Signer RA, Montecino-Rodriguez E, Witte ON, Dorshkind K. Aging and cancer resistance in lymphoid progenitors are linked processes conferred by p16Ink4a and Arf. Genes Dev. 2008 Nov 15;22(22):3115-20.
Signer RA, Montecino-Rodriguez E, Witte ON, McLaughlin J, Dorshkind K. Age-related defects in B lymphopoiesis underlie the myeloid dominance of adult leukemia. Blood. 2007 Sep 15;110(6):1831-9. Epub 2007 Jun 6