We are interested in the molecular events determining B lymphoid lineage commitment and early differentiation of B cell progenitors. Insight into the regulation of B cell development can be applied to studies of childhood lymphoblastic leukemia, a neoplasm derived from an early B lymphoid progenitor which cannot properly commit and/or differentiate into a mature B cell.

Signals for human B cell development are incompletely understood, largely due to difficulties in culturing normal human B cell progenitors. Using a bone marrow stromal dependent culture system, we have identified colony forming human lymphoid progenitors in a very early bone marrow population (CD34+/CD19-/IL-7 receptor -) which expresses early myeloid as well as lymphoid markers, and may therefore represent cells engaged in the earliest steps of commitment to two of the major hematopoietic lineages, lymphoid and myeloid. This experimental system can be used to define critical molecular events determining the commitment of early human hematopoietic progenitors to B lymphoid differentiation.

The goal of my research is to characterize the signals for lineage commitment and B lineage differentiation of these early human lymphoid progenitors. Efforts focus on analysis of immunoglobulin gene rearrangements of individual progenitors as an indicator of early B lineage commitment using advanced cell sorting and micromanipulation techniques, and transfer of B lineage specific regulatory genes directly into normal human hematopoietic progenitors to assess their contribution to B lineage commitment and development.

• Corsetti JP, Ryan D, Moss AJ, McCarthy J, Goldenberg I, Zareba W, Sparks CE. Thrombospondin-4 polymorphism (A387P) predicts cardiovascular risk in postinfarction patients with high HDL cholesterol and C-reactive protein levels. Thromb Haemost. 2011 Nov 30; 106(6):1170-8.
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• Rauh MJ, Rahman F, Good D, Silverman J, Brennan MK, Dimov N, Liesveld J, Ryan DH, Richard Burack W, Bennett JM. Blastic plasmacytoid dendritic cell neoplasm with leukemic presentation, lacking cutaneous involvement: Case series and literature review. Leuk Res. 2012 Jan; 36(1):81-6.
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• Corsetti JP, Sterry J, Sakpal M, Lefevre BH, Ryan D. Glycerol as a reference material for fecal fat quantitation using low-resolution time domain ¹H NMR spectroscopy. Clin Biochem. 2011 Nov; 44(16):1352-4.
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• Moss AJ, Francis CW, Ryan D. Collaborative clinical trials. N Engl J Med. 2011 Mar 3; 364(9):789-91.
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• Block R, Corsetti J, Goldenberg I, Vorobiof G, McNitt S, Ryan D, Zareba W, Moss AJ. The common apolipoprotein A-1 polymorphism -75A>G is associated with ethnic differences in recurrent coronary events after recovery from an acute myocardial infarction. Heart Int. 2009 Jun 30; 4(1):e8.
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• Corsetti JP, Ryan D, Rainwater DL, Moss AJ, Zareba W, Block RC, Sparks CE. Lp(a) and risk of recurrent cardiac events in obese postinfarction patients. Obesity (Silver Spring). 2008 Dec; 16(12):2717-22.
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• Goldenberg I, Moss AJ, Ryan D, Pietrasik G, Zareba W, McNitt S, Eberly SW. Cumulative burden of atherosclerotic risk genotypes and the age at onset of a first myocardial infarction: a case-only carriership approach. Ann Noninvasive Electrocardiol. 2008 Jul; 13(3):287-94.
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• Corsetti JP, Ryan D, Moss AJ, Rainwater DL, Zareba W, Sparks CE. Plasminogen activator inhibitor-1 polymorphism (4G/5G) predicts recurrence in nonhyperlipidemic postinfarction patients. Arterioscler Thromb Vasc Biol. 2008 Mar; 28(3):548-54.
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• Goldenberg I, Moss AJ, Block R, Ryan D, Corsetti JP, McNitt S, Eberly SW, Zareba W. Polymorphism in the cholesteryl ester transfer protein gene and the risk of early onset myocardial infarction among cigarette smokers. Ann Noninvasive Electrocardiol. 2007 Oct; 12(4):364-74.
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• Morray B, Goldenberg I, Moss AJ, Zareba W, Ryan D, McNitt S, Eberly SW, Glazko G, Mathew J. Polymorphisms in the paraoxonase and endothelial nitric oxide synthase genes and the risk of early-onset myocardial infarction. Am J Cardiol. 2007 Apr 15; 99(8):1100-5.
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• Corsetti JP, Ryan D, Moss AJ, Rainwater DL, Zareba W, Sparks CE. Glycoprotein Ibalpha polymorphism T145M, elevated lipoprotein-associated phospholipase A2, and hypertriglyceridemia predict risk for recurrent coronary events in diabetic postinfarction patients. Diabetes. 2007 May; 56(5):1429-35.
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• Corsetti JP, Ryan D, Moss AJ, Zareba W, Sparks CE. NAD(P)H oxidase polymorphism (C242T) and high HDL cholesterol associate with recurrent coronary events in postinfarction patients. Atherosclerosis. 2008 Jan; 196(1):461-8.
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• Goldenberg I, Moss AJ, Ryan D, McNitt S, Eberly SW, Zareba W. Polymorphism in the angiotensinogen gene, hypertension, and ethnic differences in the risk of recurrent coronary events. Hypertension. 2006 Oct; 48(4):693-9.
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• Moss AJ, Ryan D, Oakes D, Goldstein RE, Greenberg H, Bodenheimer MM, Brown MW, Case RB, Dwyer EM, Eberly SW, Francis CW, Gillespie JA, Krone RJ, Lichstein E, MacCluer JW, Marcus FI, McCarthy J, Sparks CE, Zareba W. Atherosclerotic risk genotypes and recurrent coronary events after myocardial infarction. Am J Cardiol. 2005 Jul 15; 96(2):177-82.
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• Ning L, Moss AJ, Zareba W, Robinson J, Rosero S, Ryan D, Qi M. Novel compound heterozygous mutations in the KCNQ1 gene associated with autosomal recessive long QT syndrome (Jervell and Lange-Nielsen syndrome). Ann Noninvasive Electrocardiol. 2003 Jul; 8(3):246-50.
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• Segel GB, Woodlock TJ, Xu J, Li L, Felgar RE, Ryan DH, Lichtman MA, Wang N. Early gene activation in chronic leukemic B lymphocytes induced toward a plasma cell phenotype. Blood Cells Mol Dis. 2003 May-Jun; 30(3):277-87.
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• Ross JM, Kowalchuk RM, Shaulinsky J, Ross L, Ryan D, Phatak PD. Association of heterozygous hemochromatosis C282Y gene mutation with hand osteoarthritis. J Rheumatol. 2003 Jan; 30(1):121-5.
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• Ning L, Moss A, Zareba W, Robinson J, Rosero S, Ryan D, Qi M. Denaturing high-performance liquid chromatography quickly and reliably detects cardiac ion channel mutations in long QT syndrome. Genet Test. 2003; 7(3):249-53.
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• Paeratakul S, Lovejoy JC, Ryan DH, Bray GA. The relation of gender, race and socioeconomic status to obesity and obesity comorbidities in a sample of US adults. Int J Obes Relat Metab Disord. 2002 Sep; 26(9):1205-10.
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• Phatak PD, Ryan DH, Cappuccio J, Oakes D, Braggins C, Provenzano K, Eberly S, Sham RL. Prevalence and penetrance of HFE mutations in 4865 unselected primary care patients. Blood Cells Mol Dis. 2002 Jul-Aug; 29(1):41-7.
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• Pugh-Bernard AE, Silverman GJ, Cappione AJ, Villano ME, Ryan DH, Insel RA, Sanz I. Regulation of inherently autoreactive VH4-34 B cells in the maintenance of human B cell tolerance. J Clin Invest. 2001 Oct; 108(7):1061-70.
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• Watelet LF, Moss AJ, Zareba W, Oakes D, Ryan D. Detection of a group of risk factors in coronary disease using a new carriership analysis approach. Am J Cardiol. 2000 Dec 1; 86(11):1253-6, A6.
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• Lefevre M, Lovejoy JC, DeFelice SM, Keener JW, Bray GA, Ryan DH, Hwang DH, Greenway FL. Common apolipoprotein A-IV variants are associated with differences in body mass index levels and percentage body fat. Int J Obes Relat Metab Disord. 2000 Aug; 24(8):945-53.
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• Phipps RP, Pollock SJ, Kaur K, Kaufman J, Borrello MA, Graf BA, Nazarenko D, Roberts LJ, Morrow JD, Palis J, Ryan DJ, Bennett JM. Expression of cyclooxygenase-2 and prostaglandins by B-1 cells and B-CLL cells. Curr Top Microbiol Immunol. 2000; 252:293-300.
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• Rowe JM, Rapoport AP, Ryan DH, Nilsson BI, Duerst RE, Packman CH, Abboud CN, DiPersio JF, Linder T, Wang N, Simonsson B, Liesveld JL. Treatment of chronic myelogenous leukemia with autologous bone marrow transplantation followed by roquinimex. Bone Marrow Transplant. 1999 Nov; 24(10):1057-63.
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• Ryan D, Nuccie B, Arvan D. Non-PCR-dependent detection of the factor V Leiden mutation from genomic DNA using a homogeneous invader microtiter plate assay. Mol Diagn. 1999 Jun; 4(2):135-44.
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• Ryan DH, Crowther MA, Ginsberg JS, Francis CW. Relation of factor V Leiden genotype to risk for acute deep venous thrombosis after joint replacement surgery. Ann Intern Med. 1998 Feb 15; 128(4):270-6.
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• Hu BT, Lee SC, Marin E, Ryan DH, Insel RA. Telomerase is up-regulated in human germinal center B cells in vivo and can be re-expressed in memory B cells activated in vitro. J Immunol. 1997 Aug 1; 159(3):1068-71.
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• Tang J, Nuccie BL, Ritterman I, Liesveld JL, Abboud CN, Ryan DH. TGF-beta down-regulates stromal IL-7 secretion and inhibits proliferation of human B cell precursors. J Immunol. 1997 Jul 1; 159(1):117-25.
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• Ryan DH, Nuccie BL, Ritterman I, Liesveld JL, Abboud CN, Insel RA. Expression of interleukin-7 receptor by lineage-negative human bone marrow progenitors with enhanced lymphoid proliferative potential and B-lineage differentiation capacity. Blood. 1997 Feb 1; 89(3):929-40.
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• Ryan DH, Tang J. Regulation of human B cell lymphopoiesis by adhesion molecules and cytokines. Leuk Lymphoma. 1995 May; 17(5-6):375-89.
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• Winslow JM, Liesveld JL, Ryan DH, Dipersio JF, Abboud CN. CD34+ progenitor cell isolation from blood and marrow: a comparison of techniques for small-scale selection. Bone Marrow Transplant. 1994 Aug; 14(2):265-71.
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• Ryan DH, Nuccie BL, Ritterman I, Liesveld JL, Abboud CN. Cytokine regulation of early human lymphopoiesis. J Immunol. 1994 Jun 1; 152(11):5250-8.
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• Scott G, Ewing J, Ryan D, Abboud C. Stem cell factor regulates human melanocyte-matrix interactions. Pigment Cell Res. 1994 Feb; 7(1):44-51.
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• Ryan DH. Age-specific hospital incidence rates in dementia. A record linkage study of first-admission rates to Scottish hospitals (1968-1987). Dementia. 1994 Jan-Feb; 5(1):29-35.
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• Tang J, Scott G, Ryan DH. Subpopulations of bone marrow fibroblasts support VLA-4-mediated migration of B-cell precursors. Blood. 1993 Dec 1; 82(11):3415-23.
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• Rowe J, Ryan D, Dipersio J, Gaspari A, Nilsson B, Larsson L, Liesveld J, Kouides P, Simonsson B. Autografting in chronic myelogenous leukemia followed by immunotherapy. Stem Cells. 1993 Oct; 11 Suppl 3:34-42.
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• Liesveld JL, Winslow JM, Frediani KE, Ryan DH, Abboud CN. Expression of integrins and examination of their adhesive function in normal and leukemic hematopoietic cells. Blood. 1993 Jan 1; 81(1):112-21.
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• Ryan DH. Adherence of normal and neoplastic human B cell precursors to the bone marrow microenvironment. Blood Cells. 1993; 19(2):225-41; discussion 241-4.
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• Ryan DH, Nuccie BL, Abboud CN. Inhibition of human bone marrow lymphoid progenitor colonies by antibodies to VLA integrins. J Immunol. 1992 Dec 1; 149(11):3759-64.
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• Scott G, Ryan DH, McCarthy JB. Molecular mechanisms of human melanocyte attachment to fibronectin. J Invest Dermatol. 1992 Dec; 99(6):787-94.
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• Triulzi DJ, Vanek K, Ryan DH, Blumberg N. A clinical and immunologic study of blood transfusion and postoperative bacterial infection in spinal surgery. Transfusion. 1992 Jul-Aug; 32(6):517-24.
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• Ryan DH. Phenotypic heterogeneity in acute leukemia. Clin Chim Acta. 1992 Mar 13; 206(1-2):9-23.
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• Levy PC, Utell MJ, Fleit HB, Roberts NJ, Ryan DH, Looney RJ. Characterization of human alveolar macrophage Fc gamma receptor III: a transmembrane glycoprotein that is shed under in vitro culture conditions. Am J Respir Cell Mol Biol. 1991 Oct; 5(4):307-14.
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• Ryan DH, Nuccie BL, Abboud CN, Winslow JM. Vascular cell adhesion molecule-1 and the integrin VLA-4 mediate adhesion of human B cell precursors to cultured bone marrow adherent cells. J Clin Invest. 1991 Sep; 88(3):995-1004.
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• Kitano K, Abboud CN, Ryan DH, Quan SG, Baldwin GC, Golde DW. Macrophage-active colony-stimulating factors enhance human immunodeficiency virus type 1 infection in bone marrow stem cells. Blood. 1991 Apr 15; 77(8):1699-705.
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• Liesveld JL, Winslow JM, Kempski MC, Ryan DH, Brennan JK, Abboud CN. Adhesive interactions of normal and leukemic human CD34+ myeloid progenitors: role of marrow stromal, fibroblast, and cytomatrix components. Exp Hematol. 1991 Jan; 19(1):63-70.
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• Ryan DH, Nuccie BL, Abboud CN, Liesveld JL. Maturation-dependent adhesion of human B cell precursors to the bone marrow microenvironment. J Immunol. 1990 Jul 15; 145(2):477-84.
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• Birk K, Ford C, Smeltzer S, Ryan D, Miller R, Rudick RA. The clinical course of multiple sclerosis during pregnancy and the puerperium. Arch Neurol. 1990 Jul; 47(7):738-42.
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• Anderson CL, Looney RJ, Culp DJ, Ryan DH, Fleit HB, Utell MJ, Frampton MW, Manganiello PD, Guyre PM. Alveolar and peritoneal macrophages bear three distinct classes of Fc receptors for IgG. J Immunol. 1990 Jul 1; 145(1):196-201.
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• Levy PC, Looney RJ, Shen L, Graziano RF, Fanger MW, Roberts NJ, Ryan DH, Utell MJ. Human alveolar macrophage FcR-mediated cytotoxicity. Heteroantibody- versus conventional antibody-mediated target cell lysis. J Immunol. 1990 May 15; 144(10):3693-700.
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• Perl A, DiVincenzo JP, Ryan DH, Gergely P, Szigeti A, Feher J, Abraham GN. Rearrangement of the T-cell receptor alpha, beta and gamma chain genes in chronic lymphocytic leukemia. Leuk Res. 1990; 14(2):131-7.
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• Asselin BL, Ryan D, Frantz CN, Bernal SD, Leavitt P, Sallan SE, Cohen HJ. In vitro and in vivo killing of acute lymphoblastic leukemia cells by L-asparaginase. Cancer Res. 1989 Aug 1; 49(15):4363-8.
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• Liesveld JL, Abboud CN, Duerst RE, Ryan DH, Brennan JK, Lichtman MA. Characterization of human marrow stromal cells: role in progenitor cell binding and granulopoiesis. Blood. 1989 May 15; 73(7):1794-800.
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• Perl A, Gorevic PD, Ryan DH, Condemi JJ, Ruszkowski RJ, Abraham GN. Clonal B cell expansions in patients with essential mixed cryoglobulinaemia. Clin Exp Immunol. 1989 Apr; 76(1):54-60.
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• Looney RJ, Anderson CL, Ryan DH, Rosenfeld SI. Structural polymorphism of the human platelet Fc gamma receptor. J Immunol. 1988 Oct 15; 141(8):2680-3.
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• Liesveld JL, Abboud CN, Looney RJ, Ryan DH, Brennan JK. Expression of IgG Fc receptors in myeloid leukemic cell lines. Effect of colony-stimulating factors and cytokines. J Immunol. 1988 Mar 1; 140(5):1527-33.
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• Ryan DH, Fallon MA, Horan PK. Flow cytometry in the clinical laboratory. Clin Chim Acta. 1988 Feb 15; 171(2-3):125-73.
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• Ryan DH, van Dongen JJ. Detection of residual disease in acute leukemia using immunological markers. Cancer Treat Res. 1988; 38:173-207.
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• Frantz CN, Ryan DH, Cheung NV, Duerst RE, Wilbur DC. Sensitive detection of rare metastatic human neuroblastoma cells in bone marrow by two-color immunofluorescence and cell sorting. Prog Clin Biol Res. 1988; 271:249-62.
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• Henrickson KJ, Powell KR, Ryan DH. Evaluation of acridine orange-stained buffy coat smears for identification of bacteremia in children. J Pediatr. 1988 Jan; 112(1):65-6.
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• Ryan DH, Chapple CW, Kossover SA, Sandberg AA, Cohen HJ. Phenotypic similarities and differences between CALLA-positive acute lymphoblastic leukemia cells and normal marrow CALLA-positive B cell precursors. Blood. 1987 Sep; 70(3):814-21.
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• Nikaein A, Boyer B, McQueen K, Ryan DH. Development of class I-specific helper-inducer T-cell clone. Hum Immunol. 1987 Jul; 19(3):205-14.
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• Rosenfeld SI, Ryan DH, Looney RJ, Anderson CL, Abraham GN, Leddy JP. Human Fc gamma receptors: stable inter-donor variation in quantitative expression on platelets correlates with functional responses. J Immunol. 1987 May 1; 138(9):2869-73.
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• Anderson CL, Ryan DH, Looney RJ, Leary PC. Structural polymorphism of the human monocyte 40 kilodalton Fc receptor for IgG. J Immunol. 1987 Apr 1; 138(7):2254-6.
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• Nikaein A, McQueen K, Boyer B, Landesberg R, Ryan DH, Insel RA. Functional characterization of renal infiltrating cells following allograft nephrectomy. Transplant Proc. 1987 Feb; 19(1 Pt 1):398-400.
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• Abboud CN, Duerst RE, Frantz CN, Ryan DH, Liesveld JL, Brennan JK. Lysis of human fibroblast colony-forming cells and endothelial cells by monoclonal antibody (6-19) and complement. Blood. 1986 Dec; 68(6):1196-200.
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• Anderson CL, Guyre PM, Whitin JC, Ryan DH, Looney RJ, Fanger MW. Monoclonal antibodies to Fc receptors for IgG on human mononuclear phagocytes. Antibody characterization and induction of superoxide production in a monocyte cell line. J Biol Chem. 1986 Sep 25; 261(27):12856-64.
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• Connaghan DG, Francis CW, Ryan DH, Marder VJ. Prevalence and clinical implications of heparin-associated false positive tests for serum fibrin(ogen) degradation products. Am J Clin Pathol. 1986 Sep; 86(3):304-10.
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• Duerst RE, Ryan DH, Frantz CN. Variables affecting the killing of cultured human neuroblastoma cells with monoclonal antibody and complement. Cancer Res. 1986 Jul; 46(7):3420-5.
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• Perl A, Looney RJ, Ryan DH, Abraham GN. The low affinity 40,000 Fc gamma receptor and the transferrin receptor can be alternative or simultaneous target structures on cells sensitive for natural killing. J Immunol. 1986 Jun 15; 136(12):4714-20.
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• Ohyashiki K, Yoshida MA, Gibas LM, Ohyashiki JH, Katsunuma H, Ryan DH, Rowe J, Sandberg AA. Cytogenetic changes at 11q11, 11q23, and 17q11 in myelodysplastic syndrome. Cancer Genet Cytogenet. 1986 Apr 15; 21(4):287-95.
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• Looney RJ, Ryan DH, Takahashi K, Fleit HB, Cohen HJ, Abraham GN, Anderson CL. Identification of a second class of IgG Fc receptors on human neutrophils. A 40 kilodalton molecule also found on eosinophils. J Exp Med. 1986 Apr 1; 163(4):826-36.
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• Ohyashiki K, Kocova M, Ohyashiki JH, Ryan DH, Rowe JM, Sandberg AA. Translocation between chromosomes 1 and 9 in childhood acute lymphoblastic leukemia. Cancer Genet Cytogenet. 1986 Mar 1; 21(1):5-10.
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• Ohyashiki K, Kocova M, Ryan DH, Rowe JM, Sandberg AA. Secondary acute myeloblastic leukemia with a Ph translocation in a treated Wegener's granulomatosis. Cancer Genet Cytogenet. 1986 Jan 15; 19(3-4):331-3.
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• Frantz CN, Duerst RE, Ryan DH, Constine LS, Gelsomino N, Rust L, Gregory P. A monoclonal anti-neuroblastoma antibody that discriminates between human nonhematopoietic and hematopoietic cell types. Hybridoma. 1986; 5(4):297-306.
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• Whitin JC, Ryan DH, Cohen HJ. Graded responses of human neutrophils induced by serum-treated zymosan. Blood. 1985 Nov; 66(5):1182-8.
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• Segel GB, Ryan DH, Lichtman MA. Ecto-nucleotide triphosphatase activity of human lymphocytes: studies of normal and CLL lymphocytes. J Cell Physiol. 1985 Sep; 124(3):424-32.
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• Frantz CN, Duerst RE, Ryan DH, Gelsomino NL, Constine LS, Gregory PK. Anti-neuroblastoma monoclonal antibodies which do not bind to bone marrow cells. Prog Clin Biol Res. 1985; 175:485-99.
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• Ryan DH, Mitchell SJ, Hennessy LA, Bauer KD, Horan PK, Cohen HJ. Improved detection of rare CALLA-positive cells in peripheral blood using multiparameter flow cytometry. J Immunol Methods. 1984 Nov 16; 74(1):115-28.
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