Now showing items 1-20 of 22

    • 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 ...
    • AZD2171, a Pan-VEGF Receptor Tyrosine Kinase Inhibitor, Normalizes Tumor Vasculature and Alleviates Edema in Glioblastoma Patients 

      Batchelor, Tracy Todd; Sorensen, A; di Tomaso, Emmanuelle; Zhang, Wei-Ting; Duda, Dan Gabriel; Cohen, Kenneth S.; Kozak, Kevin R.; Cahill, Daniel P.; Chen, Poe-Jou; Zhu, Mingwang; Ancukiewicz, Marek; Mrugala, Maciej M.; Plotkin, Scott Randall; Drappatz, Jan; Louis, David N.; Ivy, Percy; Scadden, David Thomas; Benner, Thomas; Loeffler, Jay Steven; Wen, Patrick Yung Chih; Jain, Rakesh K. (Elsevier BV, 2007)
      Using MRI techniques, we show here that normalization of tumor vessels in recurrent glioblastoma patients by daily administration of AZD2171—an oral tyrosine kinase inhibitor of VEGF receptors—has rapid onset, is prolonged ...
    • Bayesian approach to single-cell differential expression analysis 

      Kharchenko, Peter Vasili; Silberstein, Lev; Scadden, David Thomas (Springer Nature, 2014)
      Single-cell data provide a means to dissect the composition of complex tissues and specialized cellular environments. However, the analysis of such measurements is complicated by high levels of technical noise and intrinsic ...
    • Differential regulation of myeloid leukemias by the bone marrow microenvironment 

      Krause, Daniela S.; Fulzele, Keertik; Catic, Andre; Sun, Chia Chi; Dombkowski, David; Hurley, Michael P.; Lezeau, Sanon; Attar, Eyal; Wu, Joy Y.; Lin, Herbert Y.; Divieti-Pajevic, Paola; Hasserjian, Robert P.; Schipani, Ernestina; Van Etten, Richard A.; Scadden, David T. (2013)
      Like their normal hematopoietic stem cell counterparts, leukemia stem cells (LSC) in chronic myelogenous leukemia (CML) and acute myeloid leukemia (AML) are presumed to reside in specific niches in the bone marrow ...
    • Differential Stem and Progenitor Cell Trafficking by Prostaglandin E2 

      Hoggatt, Jonathan; Mohammad, Khalid S.; Singh, Pratibha; Hoggatt, Amber F.; Chitteti, Brahmananda Reddy; Speth, Jennifer M.; Hu, Peirong; Poteat, Bradley A.; Stilger, Kayla N.; Ferraro, Francesca; Silberstein, Lev; Wong, Frankie K.; Farag, Sherif S.; Czader, Magdalena; Milne, Ginger L.; Breyer, Richard M.; Serezani, Carlos H.; Scadden, David T.; Guise, Theresa; Srour, Edward F.; Pelus, Louis M. (2013)
      SUMMARY To maintain lifelong production of blood cells, hematopoietic stem cells (HSC) are tightly regulated by inherent programs and extrinsic regulatory signals received from their microenvironmental niche. Long-term ...
    • Direct measurement of local oxygen concentration in the bone marrow of live animals 

      Spencer, Joel A.; Ferraro, Francesca; Roussakis, Emmanuel; Klein, Alyssa; Wu, Juwell; Runnels, Judith M.; Zaher, Walid; Mortensen, Luke J.; Alt, Clemens; Turcotte, Raphaël; Yusuf, Rushdia; Côté, Daniel; Vinogradov, Sergei A.; Scadden, David T.; Lin, Charles P. (2014)
      Characterizing how the microenvironment, or niche, regulates stem cell activity is central to understanding stem cell biology and to developing strategies for therapeutic manipulation of stem cells1. Low oxygen tension ...
    • Distinct bone marrow blood vessels differentially regulate haematopoiesis 

      Itkin, Tomer; Gur-Cohen, Shiri; Spencer, Joel A.; Schajnovitz, Amir; Ramasamy, Saravana K.; Kusumbe, Anjali P.; Ledergor, Guy; Jung, Yookyung; Milo, Idan; Poulos, Michael G.; Kalinkovich, Alexander; Ludin, Aya; Kollet, Orit; Shakhar, Guy; Butler, Jason M.; Rafii, Shahin; Adams, Ralf H.; Scadden, David Thomas; Lin, Charles P.; Lapidot, Tsvee (Springer Nature, 2016)
      Bone marrow (BM) endothelial cells (BMECs) form a network of blood vessels (BVs) which regulate both leukocyte trafficking and hematopoietic stem and progenitor cell (HSPC) maintenance. However, it is not clear how BMECs ...
    • 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 ...
    • Guanine Nucleotide Exchange Factor Vav1 Regulates Perivascular Homing and Bone Marrow Retention of Hematopoietic Stem and Progenitor Cells 

      Sanchez-Aguilera, Abel; Lee, Yun-Jung; Lo Celso, Cristina; Ferraro, Francesca; Brumme, Kristina; Mondal, Subhanjan; Kim, Chaekyun; Dorrance, Adrienne; Luo, Hongbo; Scadden, David Thomas; Williams, David Allan (Proceedings of the National Academy of Sciences, 2011)
      Engraftment and maintenance of hematopoietic stem and progenitor cells (HSPC) depend on their ability to respond to extracellular signals from the bone marrow microenvironment, but the critical intracellular pathways ...
    • 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 ...
    • Inhibiting stromal cell heparan sulfate synthesis improves stem cell mobilization and enables engraftment without cytotoxic conditioning 

      Saez, Borja; Ferraro, F.; Yusuf, Rushdia Zareen; Cook, Colleen M.; Yu, Vionnie Wing Chi; Pardo-Saganta, A.; Sykes, Stephen M.; Palchaudhuri, Rahul; Schajnovitz, Amir; Lotinun, S; Lymperi, Stefania; Mendez-Ferrer, Simon; del Toro, Raquel; Day, Robyn Rouviere; Vasic, Radovan; Acharya, Sanket Shyamkant; Baron, Roland; Lin, Charles P.; Yamaguchi, Yu; Wagers, Amy Jo; Scadden, David Thomas (American Society of Hematology, 2014)
      The glycosyltransferase gene, Ext1, is essential for heparan sulfate production. Induced deletion of Ext1 selectively in Mx1-expressing bone marrow (BM) stromal cells, a known population of skeletal stem/progenitor cells, ...
    • MicroRNA miR-125a Controls Hematopoietic Stem Cell Number 

      Guo, Shangqin; Lu, Jun; Schlanger, Rita; Zhang, Hao; Wang, Judy Y.; Fox, Michelle Caroline; Purton, Louise E.; Fleming, Heather H.; Cobb, Bradley; Merkenschlager, Matthias; Golub, Todd R.; Scadden, David Thomas (National Academy of Sciences, 2010)
      MicroRNAs influence hematopoietic differentiation, but little is known about their effects on the stem cell state. Here, we report that the microRNA processing enzyme Dicer is essential for stem cell persistence in vivo ...
    • MicroRNA-Mediated Control of Cell Fate in Megakaryocyte-Erythrocyte Progenitors 

      Lu, Jun; Guo, Shangqin; Ebert, Benjamin L.; Zhang, Hao; Peng, Xiao; Bosco, Jocelyn; Pretz, Jennifer Lee; Schlanger, Rita; Wang, Judy Y.; Mak, Raymond Heungwing; Dombkowski, David M.; Preffer, Frederic Ira; Scadden, David Thomas; Golub, Todd Robert (Elsevier BV, 2008)
      Lineage specification is a critical issue in developmental and regenerative biology. We hypothesized that microRNAs (miRNAs) are important participants in that process and used the poorly-understood regulation of ...
    • Myocardial Infarction Activates CCR2+ Hematopoietic Stem and Progenitor Cells 

      Dutta, Partha; Sager, Hendrik B; Stengel, Kristy R.; Naxerova, Kamila; Courties, Gabriel P; Saez, Borja; Silberstein, Lev; Heidt, Timo; Sebas, Matthew; Sun, Yuan; Wojtkiewicz, Gregory; Feruglio, Paolo Fumene; King, Kevin Robert; Baker, Joshua N.; van der Laan, Anja M.; Borodovsky, Anna; Fitzgerald, Kevin; Hulsmans, Maarten; Hoyer, Friedrich Felix; Iwamoto, Yoshiko; Vinegoni, Claudio; Brown, Dennis; Di Carli, Marcelo; Libby, Peter; Hiebert, Scott W.; Scadden, David Thomas; Swirski, Filip K.; Weissleder, Ralph; Nahrendorf, Matthias (Elsevier BV, 2015)
      Following myocardial infarction (MI), myeloid cells derived from the hematopoietic system drive a sharp increase in systemic leukocyte levels that correlates closely with mortality. The origin of these myeloid cells, and ...
    • 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 ...
    • A Novel Role for CCL3 (MIP-1α) in Myeloma-induced Bone Disease via Osteocalcin Downregulation and Inhibition of Osteoblast Function 

      Vallet, Sonia; Pozzi, Samantha; Patel, Kishan; Vaghela, Nileshwari; Fulciniti, MariaTeresa; Veiby, Petter; Hideshima, Teru; Santo, Loredana; Cirstea, Diana; Scadden, David T; Anderson, Kenneth C; Raje, Noopur (2014)
      Upregulation of cytokines and chemokines is a frequent finding in multiple myeloma (MM). CCL3 (also known as MIP-1α) is a pro-inflammatory chemokine whose levels in the MM microenvironment correlate with osteolytic lesions ...
    • Role of the Osteoblast Lineage in the Bone Marrow Hematopoietic Niches 

      Wu, Joy Yee-Jia; Scadden, David Thomas; Kronenberg, Henry Morris (The American Society for Bone and Mineral Research, 2009)
    • Sex steroid blockade enhances thymopoiesis by modulating Notch signaling 

      Velardi, Enrico; Tsai, Jennifer J.; Holland, Amanda M.; Wertheimer, Tobias; Yu, Vionnie W.C.; Zakrzewski, Johannes L.; Tuckett, Andrea Z.; Singer, Natalie V.; West, Mallory L.; Smith, Odette M.; Young, Lauren F.; Kreines, Fabiana M.; Levy, Emily R.; Boyd, Richard L.; Scadden, David T.; Dudakov, Jarrod A.; van den Brink, Marcel R.M. (The Rockefeller University Press, 2014)
      Paradoxical to its importance for generating a diverse T cell repertoire, thymic function progressively declines throughout life. This process has been at least partially attributed to the effects of sex steroids, and their ...
    • 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 ...