Publications

Tumorigenic potential is restored during differentiation in fusion-reprogrammed cancer cells

Yao J, Zhang L, Hu L, Guo B, Hu X, Borjigin U, Wei Z, Chen Y, Lv M, Lau JT, Wang X, Li G, Hu YP. Cell Death Dis. 2016 Jul 28;7(7):e2314. doi: 10.1038/cddis.2016.189. PMID: 27468690 Abstract Detailed understanding of the mechanistic … Continued

Glycoengineering of E-Selectin Ligands by Intracellular versus Extracellular Fucosylation Differentially Affects Osteotropism of Human Mesenchymal Stem Cells

Dykstra B, Lee J, Mortensen LJ, Yu H, Wu ZL, Lin CP, Rossi DJ, Sackstein R. Stem Cells. 2016 Oct;34(10):2501-2511. doi: 10.1002/stem.2435. PMID: 27335219 Abstract Human mesenchymal stem cells (MSCs) hold great promise in cellular therapeutics for skeletal diseases but lack expression … Continued

Platelet clearance by the hepatic Ashwell-Morrell receptor: mechanisms and biological significance

Hoffmeister KM, Falet H. Thromb Res. 2016 May;141 Suppl 2:S68-72. doi: 10.1016/S0049-3848(16)30370-X. PMID: 27207430 Abstract The daily production of billions of platelets must be regulated to avoid spontaneous bleeding or arterial occlusion and organ damage. Complex mechanisms control platelet production and clearance … Continued

Glycans and the platelet life cycle

Li R, Hoffmeister KM, Falet H. Platelets. 2016 Sep;27(6):505-11. doi: 10.3109/09537104.2016.1171304. PMID: 27135356 Abstract Platelet numbers are intricately regulated to avoid spontaneous bleeding or arterial occlusion and organ damage. The growth factor thrombopoietin (TPO) drives platelet biogenesis by inducing megakaryocyte production. A … Continued

Fulfilling Koch’s postulates in glycoscience: HCELL, GPS and translational glycobiology

Sackstein R. Glycobiology. 2016 Jun;26(6):560-70. doi: 10.1093/glycob/cww026. Review. PMID: 26933169 Abstract Glycoscience-based research that is performed expressly to address medical necessity and improve patient outcomes is called “translational glycobiology”. In the 19th century, Robert Koch proposed a set of postulates to rigorously … Continued

Regulating billions of blood platelets: glycans and beyond

Grozovsky R, Giannini S, Falet H, Hoffmeister KM. Blood. 2015 Oct 15;126(16):1877-84. doi: 10.1182/blood-2015-01-569129. Review. PMID: 26330242 Abstract The human body produces and removes 10(11) platelets daily to maintain a normal steady state platelet count. Platelet production must be regulated to avoid … Continued

2015 proceedings of the National Heart, Lung, and Blood Institute’s State of the Science in Transfusion Medicine symposium.

Spitalnik SL, Triulzi D, Devine DV, Dzik WH, Eder AF, Gernsheimer T, Josephson CD, Kor DJ, Luban NL, Roubinian NH, Mondoro T, Welniak LA, Zou S, Glynn S; State of the Science in Transfusion Medicine Working Groups.. Transfusion. 2015 Sep;55(9):2282-90. doi: … Continued

Desialylation is a mechanism of Fc-independent platelet clearance and a therapeutic target in immune thrombocytopenia

Li J, van der Wal DE, Zhu G, Xu M, Yougbare I, Ma L, Vadasz B, Carrim N, Grozovsky R, Ruan M, Zhu L, Zeng Q, Tao L, Zhai ZM, Peng J, Hou M, Leytin V, Freedman J, Hoffmeister KM, … Continued

Novel mechanisms of platelet clearance and thrombopoietin regulation

Grozovsky R, Giannini S, Falet H, Hoffmeister KM. Curr Opin Hematol. 2015 Sep;22(5):445-51. doi: 10.1097/MOH.0000000000000170. Review. PMID: 26154508 Abstract PURPOSE OF REVIEW: The human body produces and removes 10 platelets daily to maintain a normal steady-state platelet count. Platelet production must be … Continued

Cell surface glycan engineering of neural stem cells augments neurotropism and improves recovery in a murine model of multiple scleros

Merzaban JS, Imitola J, Starossom SC, Zhu B, Wang Y, Lee J, Ali AJ, Olah M, Abuelela AF, Khoury SJ, Sackstein R. Glycobiology. 2015 Dec;25(12):1392-409. doi: 10.1093/glycob/cwv046. PMID: 26153105 Abstract Neural stem cell (NSC)-based therapies offer potential for neural repair in central … Continued

Progress and obstacles towards generating hematopoietic stem cells from pluripotent stem cells

Lee J, Dykstra B, Sackstein R, Rossi DJ. Curr Opin Hematol. 2015 Jul;22(4):317-23. doi: 10.1097/MOH.0000000000000147. Review. PMID: 26049752 Abstract PURPOSE OF REVIEW: Human pluripotent stem cells (PSCs) have the potential to provide an inexhaustible source of hematopoietic stem cells (HSCs) that could … Continued

Integration of systems glycobiology with bioinformatics toolboxes, glycoinformatics resources, and glycoproteomics data

Liu G, Neelamegham S. Wiley Interdiscip Rev Syst Biol Med. 2015 Jul-Aug;7(4):163-81. doi: 10.1002/wsbm.1296. Review. PMID: 25871730 Abstract The glycome constitutes the entire complement of free carbohydrates and glycoconjugates expressed on whole cells or tissues. ‘Systems Glycobiology’ is an emerging discipline that … Continued

FlnA binding to PACSIN2 F-BAR domain regulates membrane tubulation in megakaryocytes and platelets

Begonja AJ, Pluthero FG, Suphamungmee W, Giannini S, Christensen H, Leung R, Lo RW, Nakamura F, Lehman W, Plomann M, Hoffmeister KM, Kahr WH, Hartwig JH, Falet H. Blood. 2015 Jul 2;126(1):80-8. doi: 10.1182/blood-2014-07-587600. PMID: 25838348 Abstract Bin-Amphiphysin-Rvs (BAR) and Fes-CIP4 homology … Continued

HCELL Expression on Murine MSC Licenses Pancreatotropism and Confers Durable Reversal of Autoimmune Diabetes in NOD Mice

Abdi R, Moore R, Sakai S, Donnelly CB, Mounayar M, Sackstein R. Stem Cells. 2015 May;33(5):1523-31. doi: 10.1002/stem.1948. PMID: 25641589 Abstract Type 1 diabetes (T1D) is an immune-mediated disease resulting in destruction of insulin-producing pancreatic beta cells. Mesenchymal stem cells (MSCs) possess … Continued

The structures of glycophorin C N-glycans, a putative component of the GPC receptor site for Plasmodium falciparum EBA-140 ligand

Ashline DJ, Duk M, Lukasiewicz J, Reinhold VN, Lisowska E, Jaskiewicz E. Glycobiology. 2015 May;25(5):570-81. doi: 10.1093/glycob/cwu188. PMID: 25552259 Abstract Glycophorins C and D are highly glycosylated integral sialoglycoproteins of human red blood cell membranes carrying the Gerbich blood group antigens. The … Continued

The glycosylation-dependent interaction of perlecan core protein with LDL: implications for atherosclerosis

Xu YX, Ashline D, Liu L, Tassa C, Shaw SY, Ravid K, Layne MD, Reinhold V, Robbins PW. J Lipid Res. 2015 Feb;56(2):266-76. doi: 10.1194/jlr.M053017. PMID: 25528754 Abstract Perlecan is a major heparan sulfate (HS) proteoglycan in the arterial wall. Previous studies … Continued

Tools to MSn Sequence and Document the Structures of Glycan Epitopes

Zhang H, Ashline DJ, Reinhold VN. Discov Subtleties Sugars (2013). 2014 Dec 22;2013:117-131. PMID: 27110600 Abstract Sequential disassembly (MSn) has been applied to fully characterise and document native samples containing glycan epitopes with their synthetic analogues. Both sample types were prepared by … Continued

ST3Gal-4 is the primary sialyltransferase regulating the synthesis of E-, P-, and L-selectin ligands on human myeloid leukocytes

Mondal N, Buffone A Jr, Stolfa G, Antonopoulos A, Lau JT, Haslam SM, Dell A, Neelamegham S. Blood. 2015 Jan 22;125(4):687-96. doi: 10.1182/blood-2014-07-588590. PMID: 25498912 Abstract The precise glycosyltransferase enzymes that mediate selectin-ligand biosynthesis in human leukocytes are unknown. This knowledge is … Continued

The Ashwell-Morell receptor regulates hepatic thrombopoietin production via JAK2-STAT3 signaling

Grozovsky R, Begonja AJ, Liu K, Visner G, Hartwig JH, Falet H, Hoffmeister KM. Nat Med. 2015 Jan;21(1):47-54. doi: 10.1038/nm.3770. PMID: 25485912 Abstract The hepatic Ashwell-Morell receptor (AMR) can bind and remove desialylated platelets. Here we demonstrate that platelets become desialylated as … Continued

Dynamin 2-dependent endocytosis is required for normal megakaryocyte development in mice

Bender M, Giannini S, Grozovsky R, Jönsson T, Christensen H, Pluthero FG, Ko A, Mullally A, Kahr WH, Hoffmeister KM, Falet H. Blood. 2015 Feb 5;125(6):1014-24. doi: 10.1182/blood-2014-07-587857. PMID: 25468568 Abstract Dynamins are highly conserved large GTPases (enzymes that hydrolyze guanosine triphosphate) … Continued

Protein and site specificity of fucosylation in liver-secreted glycoproteins

Pompach P, Ashline DJ, Brnakova Z, Benicky J, Sanda M, Goldman R. J Proteome Res. 2014 Dec 5;13(12):5561-9. doi: 10.1021/pr5005482. PMID: 25265424 Abstract Chronic liver diseases are a serious health problem worldwide. One of the frequently reported glycan alterations in liver disease … Continued

The mechanisms of up-regulation of dendritic cell activity by oxidative stress

Batal I, Azzi J, Mounayar M, Abdoli R, Moore R, Lee JY, Rosetti F, Wang C, Fiorina P, Sackstein R, Ichimura T, Abdi R. (2014) The mechanisms of up-regulation of dendritic cell activity by oxidative stress. J Leukoc Biol. 96(2):283-93. … Continued

Molecular mechanisms regulating platelet clearance and thrombopoietin production.

Grozovsky R, Falet H, Hoffmeister KM. (2014) Molecular mechanisms regulating platelet clearance and thrombopoietin production. Vox Sanguinis, in press. 3339–3347.

G-CSF Induces Membrane Expression of a Myeloperoxidase Glycovariant that Operates as an E-selectin Ligand on Human Myeloid Cells

Silvescu C, Sackstein R. (2014) G-CSF Induces Membrane Expression of a Myeloperoxidase Glycovariant that Operates as an E-selectin Ligand on Human Myeloid Cells. Proc Natl Acad Sci U S A. 111(29):10696-701. PMID: 25002508. PMCID: PMC4115493. Abstract The host defense response … Continued

A computational framework for the automated construction of glycosylation reaction networks.

Liu G, Neelamegham S. (2014) A computational framework for the automated construction of glycosylation reaction networks. PLoS One. 9(6):e100939. doi: 10.1371/journal.pone.0100939. eCollection 2014. PMID: 24978019. PMCID: PMC4076241. Abstract Glycosylation is among the most common and complex post-translational modifications identified to … Continued

Congenital disorder of fucosylation type 2c (LADII) presenting with short stature and developmental delay with minimal adhesion defect.

Dauber A, Ercan A, Lee J, James P, Jacobs PP, Ashline DJ, Wang SR, Miller T, Hirschhorn JN, Nigrovic PA, Sackstein R. (2014) Congenital disorder of fucosylation type 2c (LADII) presenting with short stature and developmental delay with minimal adhesion … Continued

Platelets support extracellular sialylation by supplying the sugar donor substrate.

Lee MM1, Nasirikenari M, Manhardt CT, Ashline DJ, Hanneman AJ, Reinhold VN, Lau JT. (2014) Platelets support extracellular sialylation by supplying the sugar donor substrate. J Biol Chem. 289(13):8742-8. PMID: 24550397; PMCID: PMC3979374   Abstract Sizable pools of freely circulating glycosyltransferases are in blood, but understanding their physiologic contributions has been … Continued

Expansion of the neonatal platelet mass is achieved via an extension of platelet lifespan.

Liu ZJ, Hoffmeister KM, Hu Z, Mager DE, Ait-Oudhia S, Debrincat MA, Pleines I, Josefsson EC, Kile BT, Italiano J Jr, Ramsey H, Grozovsky R, Veng-Pedersen P, Chavda C, Sola-Visner M. (2014) Expansion of the neonatal platelet mass is achieved … Continued

No monkeying around: clonal tracking of stem cells and progenitors in the macaque.

Dykstra B, Bystrykh LV. (2014) No monkeying around: clonal tracking of stem cells and progenitors in the macaque. Cell Stem Cell. 14(4):419-20. PMID: 24702990 Abstract Clonal tracking of hematopoietic stem and progenitor cells (HSPCs) has proven valuable for studying their behavior in murine recipients. Now in … Continued

Structural documentation of glycan epitopes: sequential mass spectrometry and spectral matching

Ashline DJ, Hanneman AJ, Zhang H, Reinhold VN. (2014) Structural documentation of glycan epitopes: sequential mass spectrometry and spectral matching. J Am Soc Mass Spectrom. 25(3):444-53. PMID: 24385394. PMCID: PMC3950938. Abstract Documenting mass spectral data is a fundamental aspect of … Continued

Remodeling of marrow hematopoietic stem and progenitor cells by non-self ST6Gal-1 sialyltransferase.

Nasirikenari M, Veillon L, Collins CC, Azadi P, Lau JT. (2014) Remodeling of marrow hematopoietic stem and progenitor cells by non-self ST6Gal-1 sialyltransferase. J Biol Chem. 289(10):7178-89. PMID: 24425878. PMCID: PMC3945377. Abstract Glycans occupy the critical cell surface interface between … Continued

Wiskott-Aldrich syndrome protein (WASp) controls the delivery of platelet transforming growth factor-β1.

Kim H, Falet H, Hoffmeister KM, Hartwig JH. (2013) Wiskott-Aldrich syndrome protein (WASp) controls the delivery of platelet transforming growth factor-β1. J Biol Chem. 288(48):34352-63. PMID: 24133214; PMCID: PMC3843050 Abstract Platelets are immunologically competent cells containing cytokines such as TGF-β1 that regulate cell-mediated immunity. However, the mechanisms underlying … Continued

Toward a platform for comprehensive glycan sequencing.

Reinhold V, Zhang H, Hanneman A, Ashline D. (2013) Toward a platform for comprehensive glycan sequencing. Mol Cell Proteomics. 12(4):866-73. PMID: 23438731; PMCID: PMC3617333 Abstract From a series of recently published reports, an analytical platform has been proposed for a quantitative and qualitative measure of N- and O-glycosylation, complete … Continued

Glycosylation Network Analysis Toolbox: a MATLAB-based environment for systems glycobiology.

Liu G, Puri A, Neelamegham S. (2013) Glycosylation Network Analysis Toolbox: a MATLAB-based environment for systems glycobiology. Bioinformatics. 29(3):404-6. PMID: 23230149; PMCID: PMC3562062   Abstract Systems glycobiology studies the interaction of various pathways that regulate glycan biosynthesis and function. Software tools for the construction and analysis of such … Continued

Silencing α1,3-fucosyltransferases in human leukocytes reveals a role for FUT9 during E-selectin mediated cell adhesion

Buffone A Jr, Mondal N, Gupta R, McHugh KP, Lau JT, Neelamegham S. (2013) Silencing α1,3-fucosyltransferases in human leukocytes reveals a role for FUT9 during E-selectin mediated cell adhesion. J Biol Chem. 288(3):1620-1633. PMID: 23192350; PMCID: PMC3548472   Abstract Leukocyte … Continued

The phagocytic capacity and immunological potency of human dendritic cells is improved by α2,6-sialic acid deficiency.

Cabral MG, Silva Z, Ligeiro D, Seixas E, Crespo H, Carrascal MA, Silva M, Piteira AR, Paixão P, Lau JT, Videira PA. (2012) The phagocytic capacity and immunological potency of human dendritic cells is improved by α2,6-sialic acid deficiency. Immunology. 138(3):235-245. PMID: 23113614; PMCID: PMC3573277   Abstract Dendritic cells (DCs) play an essential role in … Continued

Death regulates platelet birth and life.

Hoffmeister KM. (2012) Death regulates platelet birth and life. Blood. 119(24):5617-8. PMID: 22700694 Comment on Mcl-1 and Bcl-x(L) coordinately regulate megakaryocyte survival. [Blood. 2012] Link to journal: http://www.bloodjournal.org/?sso-checked=true

The origin and function of platelet glycotransferases.

Wandall HH, Rumjantseva V, Sørensen AL, Patel-Hett S, Josefsson EC, Bennett EP, Italiano JE Jr, Clausen H, Hartwig JH, Hoffmeister KM. (2012) The origin and function of platelet glycotransferases. Bone. 120(3):626-35. PMID: 22613794; PMCID: PMC3401214. Link to journal: http://www.journals.elsevier.com/bone/

Anti-inflammatory IgG production requires functional P1 promoter in β-galactoside α2,6-sialyltransferase 1 (ST6Gal-1) gene.

Jones MB, Nasirikenari M, Lugade AA, Thanavala Y, Lau JT.(2012) Anti-inflammatory IgG production requires functional P1 promoter in β-galactoside α2,6-sialyltransferase 1 (ST6Gal-1) gene. J Biol Chem. 287(19):15365-70. PMID: 22427662; PMCID: PMC3346113. Link to journal: http://www.jbc.org/

Engineering cellular trafficking via glycosyltransferase-programmed stereosubstitution.

Sackstein R. (2012) Engineering cellular trafficking via glycosyltransferase-programmed stereosubstitution. Ann N Y Acad Sci. 1253:193-200. doi: 10.1111/j.1749-6632.2011.06421.x. PMID: 22352800; PMCID: PMC3336002. Abstract The proximate hurdle for cell trafficking to any anatomic site is the initial attachment of circulating cells to target … Continued

Polymorphism in the protease-activated receptor-4 gene region associates with platelet activation and perioperative myocardial injury.

Muehlschlegel JD, Perry TE, Liu KY, Fox AA, Smith SA, Lichtner P, Collard CD, Shernan SK, Hartwig JH, Body SC, Hoffmeister KM. (2012) Polymorphism in the protease-activated receptor-4 gene region associates with platelet activation and perioperative myocardial injury. Am J … Continued

Desialylation accelerates platelet clearance after refrigeration and initiates GPIbα metalloproteinase-mediated cleavage in mice.

Jansen AJ, Josefsson EC, Rumjantseva V, Liu QP, Falet H, Bergmeier W, Cifuni SM, Sackstein R, von Andrian UH, Wagner DD, Hartwig JH, Hoffmeister KM. (2012) Desialylation accelerates platelet clearance after refrigeration and initiates GPIbα metalloproteinase-mediated cleavage in mice. Blood. … Continued

CD44 and HCELL: preventing hematogenous metastasis at step 1.

Jacobs PP, Sackstein R. (2011) CD44 and HCELL: preventing hematogenous metastasis at step 1. FEBS Lett. 585(20):3148-58. PMID: 21827751; PMCID: PMC3195965. Abstract Despite great strides in our knowledge of the genetic and epigenetic changes underlying malignancy, we have limited information on … Continued

Understanding glycomechanics using mathematical modeling: a review of current approaches to simulate cellular glycosylation reaction networks.

Puri A, Neelamegham S. (2012) Understanding glycomechanics using mathematical modeling: a review of current approaches to simulate cellular glycosylation reaction networks. Ann Biomed Eng. (4):816-27. PMID: 22090146; PMCID: PMC3311736. Abstract Following the footsteps of genomics and proteomics, recent years have witnessed … Continued

Glycoengineering of HCELL, the human bone marrow homing receptor: sweetly programming cell migration.

Sackstein R. (2012) Glycoengineering of HCELL, the human bone marrow homing receptor: sweetly programming cell migration. Ann Biomed Eng. 40(4):766-76. PMID: 22068886; PMCID: PMC3311703. Abstract The successful clinical implementation of adoptive cell therapeutics, including bone marrow transplantation and other stem cell-based … Continued