Browsing by Author "Sykes, David"
Now showing items 1-20 of 20
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Amino acid–insensitive mTORC1 regulation enables nutritional stress resilience in hematopoietic stem cells
Kalaitzidis, Demetrios; Lee, Dongjun; Efeyan, Alejo; Kfoury, Youmna Sami; Nayyar, Naema; Sykes, David Brian; Mercier, Francois; Papazian, Ani Elizabeth; Baryawno, Ninib; Victora, Gabriel D.; Neuberg, Donna S.; Sabatini, David Alexander; Scadden, David Thomas (American Society for Clinical Investigation, 2017)The mTOR pathway is a critical determinant of cell persistence and growth wherein mTOR complex 1 (mTORC1) mediates a balance between growth factor stimuli and nutrient availability. Amino acids or glucose facilitates mTORC1 ... -
Case report: a 37-year-old male with telangiectasias, polycythemia vera, perinephric fluid collections, and intrapulmonary shunting
Khan, Javed; Sykes, David Brian (Springer Nature, 2014)The TEMPI syndrome was recently described in 2011, and is characterized by the constellation of five hallmarks: Telangiectasias, Erythrocytosis and elevated Erythropoietin, Monoclonal gammopathy, Perinephric fluids ... -
Complete and Partial Responses of the TEMPI Syndrome to Bortezomib
Schroyens, Wilfried; O'Connell, Casey; Sykes, David Brian (New England Journal of Medicine (NEJM/MMS), 2012) -
Control of signaling-mediated clearance of apoptotic cells by the tumor suppressor p53
Yoon, K. W.; Byun, S.; Kwon, Eunjeong; Hwang, So-Young; Chu, Kiki; Hiraki, Masatsugu; Jo, Seung-Hee; Weins, Astrid; Hakroush, Samy; Cebulla, Angelika; Sykes, David Brian; Greka, Anna; Mundel, Peter; Fisher, David E.; Mandinova, Anna; Lee, Sam Whan (American Association for the Advancement of Science (AAAS), 2015)The inefficient clearance of dying cells can lead to abnormal immune responses, such as unresolved inflammation and autoimmune conditions. We show that tumor suppressor p53 controls signaling-mediated phagocytosis of ... -
Dectin-1 Activation Controls Maturation of β-1,3-Glucan-containing Phagosomes
Mansour, Michael Karim; Tam, Jenny M.; Khan, Nida S.; Seward, Michael; Davids, Peter J.; Puranam, Sravanthi; Sokolovska, Anna; Sykes, David Brian; Dagher, Zeina; Becker, Christine; Tanne, Antoine; Reedy, Jennifer L; Stuart, Lynda M.; Vyas, Jatin Mahesh (American Society for Biochemistry & Molecular Biology (ASBMB), 2013)Background: Dectin-1 is able to recognize and phagocytose the fungal carbohydrate, β-1,3-glucan, but its contribution to phagosomal maturation has not been explored. Results: Dectin-1-dependent Syk activation promotes ... -
E2a/Pbx1 Induces the Rapid Proliferation of Stem Cell Factor-Dependent Murine Pro-T Cells That Cause Acute T-Lymphoid or Myeloid Leukemias in Mice
Sykes, David Brian; Kamps, Mark P. (American Society for Microbiology, 2004)Oncoprotein E2a/Pbx1 is produced by the t(1;19) chromosomal translocation of human pre-B acute lymphoblastic leukemia. E2a/Pbx1 blocks differentiation of primary myeloid progenitors but, paradoxically, induces apoptosis ... -
Endogenous transmembrane protein UT2 inhibits pSTAT3 and suppresses hematological malignancy
Lee, Dongjun; Wang, Ying-Hua; Kalaitzidis, Demetrios; Ramachandran, Janani; Eda, Homare; Sykes, David Brian; Raje, Noopur; Scadden, David Thomas (American Society for Clinical Investigation, 2016)Regulation of STAT3 activation is critical for normal and malignant hematopoietic cell proliferation. Here, we have reported that the endogenous transmembrane protein upstream-of-mTORC2 (UT2) negatively regulates activation ... -
The hematopoietic stem cell niche
Park, Dongsu; Sykes, David Brian; Scadden, David Thomas (Frontiers in Bioscience, 2012)Hematopoietic stem cells (HSCs) possess the ability to self-renew and to differentiate to mature progeny along multiple different hematopoietic lineages. The function of HSCs depends upon the signals from surrounding cells ... -
Hoxa9 Immortalizes a Granulocyte-Macrophage Colony-Stimulating Factor-Dependent Promyelocyte Capable of Biphenotypic Differentiation to Neutrophils or Macrophages, Independent of Enforced Meis Expression
Calvo, Katherine R.; Sykes, David Brian; Pasillas, Martina; Kamps, Mark P. (American Society for Microbiology, 2000)The genes encoding Hoxa9 and Meis1 are transcriptionally coactivated in a subset of acute myeloid leukemia (AML) in mice. In marrow reconstitution experiments, coexpression of both genes produces rapid AML, while neither ... -
The HoxB1 hexapeptide is a prefolded domain: Implications for the Pbx1/Hox interaction
Slupsky, Carolyn M.; Sykes, David Brian; Gay, Grant L.; Sykes, Brian D. (Wiley-Blackwell, 2001)Hox proteins are transcriptional regulators that bind consensus DNA sequences. The DNA-binding specificity of many of these Hox proteins is modulated by the heterodimerization with partners, such as the Pbx proteins. This ... -
An Induced Ets Repressor Complex Regulates Growth Arrest during Terminal Macrophage Differentiation
Klappacher, Günter W.; Lunyak, Victoria V.; Sykes, David Brian; Sawka-Verhelle, Dominique; Sage, Julien; Brard, Gyan; Ngo, Sally D.; Gangadharan, Denise; Jacks, Tyler; Kamps, Mark P.; Rose, David W.; Rosenfeld, Michael G.; Glass, Christopher K. (Elsevier BV, 2002)Defining the molecular mechanisms that coordinately regulate proliferation and differentiation is a central issue in development. Here, we describe a mechanism in which induction of the Ets repressor METS/PE1 links terminal ... -
Meis1a suppresses differentiation by G-CSF and promotes proliferation by SCF: Potential mechanisms of cooperativity with Hoxa9 in myeloid leukemia
Calvo, K. R.; Knoepfler, P. S.; Sykes, David Brian; Pasillas, M. P.; Kamps, M. P. (Proceedings of the National Academy of Sciences, 2001)Hoxa9 and Meis1a are homeodomain transcription factors that heterodimerize on DNA and are down-regulated during normal myeloid differentiation. Hoxa9 and Meis1a cooperate to induce acute myeloid leukemia (AML) in mice, and ... -
Neuregulin1-β Decreases IL-1β -Induced Neutrophil Adhesion to Human Brain Microvascular Endothelial Cells
Wu, Limin; Walas, Samantha; Leung, Wendy; Sykes, David Brian; Wu, Jiang; Lo, Eng H.; Lok, Josephine M. (Springer Nature, 2014)Neuroinflammation contributes to the pathophysiology of diverse diseases including stroke, traumatic brain injury, Alzheimer's Disease, Parkinson's Disease, and multiple sclerosis, resulting in neurodegeneration and loss ... -
Niche-Based Screening in Multiple Myeloma Identifies a Kinesin-5 Inhibitor with Improved Selectivity over Hematopoietic Progenitors
Chattopadhyay, Shrikanta; Stewart, Alison L.; Mukherjee, Siddhartha; Huang, Cherrie; Hartwell, Kimberly A.; Miller, Peter Grant; Subramanian, Radhika; Carmody, Leigh C.; Yusuf, Rushdia Zareen; Sykes, David Brian; Paulk, Joshiawa; Vetere, Amedeo; Vallet, Sonia; Santo, Loredana; Cirstea, Diana D.; Hideshima, Teru; Dan?ík, Vlado; Majireck, Max M.; Hussain, Mahmud M.; Singh, Shambhavi; Quiroz, Ryan; Iaconelli, Jonathan; Karmacharya, Rakesh; Tolliday, Nicola J.; Clemons, Paul A.; Moore, Malcolm A.S.; Stern, Andrew M.; Shamji, Alykhan Farid; Ebert, Benjamin L.; Golub, Todd Robert; Raje, Noopur; Scadden, David Thomas; Schreiber, Stuart L. (Elsevier BV, 2015)Novel therapeutic approaches are urgently required for multiple myeloma (MM). We used a phenotypic screening approach using co-cultures of MM cells with bone marrow stromal cells to identify compounds that overcome stromal ... -
Non-genotoxic conditioning for hematopoietic stem cell transplantation using a hematopoietic-cell-specific internalizing immunotoxin
Palchaudhuri, Rahul; Saez, Borja; Hoggatt, Jonathan George; Schajnovitz, Amir; Sykes, David Brian; Tate, Tiffany A; Czechowicz, Agnieszka; Kfoury, Youmna Sami; Ruchika, FNU; Rossi, Derrick J; Verdine, Gregory L.; Mansour, Michael Karim; Scadden, David Thomas (Springer Nature, 2016)Hematopoietic stem cell transplantation (HSCT) offers curative therapy for patients with hemoglobinopathies, congenital immunodeficiencies, and other conditions, possibly including AIDS. Autologous HSCT using genetically ... -
Putative RNA-splicing gene LUC7L2 on 7q34 represents a candidate gene in pathogenesis of myeloid malignancies
Singh, H; Lane, A A; Correll, M; Przychodzen, B; Sykes, David Brian; Stone, Richard Maury; Ballen, K K; Amrein, Philip Crawford; Maciejewski, J; Attar, E C (Springer Nature, 2013) -
RECQL5 Suppresses Oncogenic JAK2-Induced Replication Stress and Genomic Instability
Chen, Edwin; Ahn, Jong Sook; Sykes, David Brian; Breyfogle, Lawrence J.; Godfrey, Anna L.; Nangalia, Jyoti; Ko, Amy; DeAngelo, Daniel J.; Green, Alexander Robert; Mullally, Ann (Elsevier BV, 2015)JAK2V617F is the most common oncogenic lesion in patients with myeloproliferative neoplasms (MPNs). Despite the ability of JAK2V617F to instigate DNA damage in vitro, MPNs are nevertheless characterized by genomic stability. ... -
SIRT1 Regulates Differentiation of Mesenchymal Stem Cells by Deacetylating β-Catenin
Simic, Petra; Zainabadi, Kayvan; Bell, Eric; Sykes, David Brian; Saez, Borja; Lotinun, Sutada; Baron, Roland; Scadden, David Thomas; Schipani, Ernestina; Guarente, Leonard (WILEY-VCH Verlag, 2013)Mesenchymal stem cells (MSCs) are multi-potent cells that can differentiate into osteoblasts, adipocytes, chondrocytes and myocytes. This potential declines with aging. We investigated whether the sirtuin SIRT1 had a ... -
The TEMPI Syndrome — A Novel Multisystem Disease
Sykes, David Brian; Schroyens, Wilfried; O'Connell, Casey (New England Journal of Medicine (NEJM/MMS), 2011) -
TH2 Cytokines and Allergic Challenge Induce Ym1 Expression in Macrophages by a STAT6-dependent Mechanism
Welch, John Crawford; Escoubet-Lozach, Laure; Sykes, David Brian; Liddiard, Kate; Greaves, David R.; Glass, Christopher K. (American Society for Biochemistry & Molecular Biology (ASBMB), 2002)The diverse functions of macrophages as participants in innate and acquired immune responses are regulated by the specific milieu of environmental factors, cytokines, and other signaling molecules that are encountered at ...