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The T-ALL Related Gene BCL11B Regulates the Initial Stages of Human T-Cell Differentiation
Leukemia (2017) 31, 2503–2514 © 2017 Macmillan Publishers Limited, part of Springer Nature. All rights reserved 0887-6924/17 www.nature.com/leu ORIGINAL ARTICLE The T-ALL related gene BCL11B regulates the initial stages of human T-cell differentiation VL Ha1, A Luong1,FLi2, D Casero3, J Malvar1,YMKim1,4, R Bhatia5, GM Crooks3,6,7,8 and C Parekh1,4 The initial stages of T-cell differentiation are characterized by a progressive commitment to the T-cell lineage, a process that involves the loss of alternative (myelo-erythroid, NK, B) lineage potentials. Aberrant differentiation during these stages can result in T-cell acute lymphoblastic leukemia (T-ALL). However, the mechanisms regulating the initial stages of human T-cell differentiation are obscure. Through loss of function studies, we showed BCL11B, a transcription factor recurrently mutated T-ALL, is essential for T-lineage commitment, particularly the repression of NK and myeloid potentials, and the induction of T-lineage genes, during the initial stages of human T-cell differentiation. In gain of function studies, BCL11B inhibited growth of and induced a T-lineage transcriptional program in T-ALL cells. We found previously unknown differentiation stage-specific DNA binding of BCL11B at multiple T-lineage genes; target genes showed BCL11B-dependent expression, suggesting a transcriptional activator role for BCL11B at these genes. Transcriptional analyses revealed differences in the regulatory actions of BCL11B between human and murine thymopoiesis. Our studies show BCL11B is a key regulator of the initial stages of human T-cell differentiation and delineate the BCL11B transcriptional program, enabling the dissection of the underpinnings of normal T-cell differentiation and providing a resource for understanding dysregulations in T-ALL. -
Collins Challenged Over NCI-Funded Research Linking Tea Party
Vol. 39 No. 10 March 8, 2013 © Copyright 2013 The Cancer Letter Inc. All rights reserved. Price $405 Per Year. To subscribe, call 800-513-7042 or visit www.cancerletter.com. PO Box 9905 Washington DC 20016 Telephone 202-362-1809 Capitol Hill Collins Challenged Over NCI-Funded Research Capitol Hill Linking Tea Party With Tobacco Companies Collins: "I am quite By Paul Goldberg troubled by this NIH Director Francis Collins told a House subcommittee that he was “troubled” by a paper in which a prominent tobacco control expert, who particular circumstance." is funded by NCI, claims to have found a relationship between tobacco . Page 4 companies and the Tea Party conservative movement. The paper in question appeared in Tobacco Control, a peer-reviewed journal published by British Medical Journal Group. Drawing on documents Sequestration dating back to the 1980s and obtained from tobacco companies, the authors NCI Director Harold point to several instances in which the Tea Party and its predecessor Varmus Seeks to Protect organizations appear to act as proxies for tobacco interests. The paper cites Competitive Awards an NCI grant that supports analysis of tobacco industry documents. Page 5 The paper’s senior author is Stanton Glantz, professor in the Department of Medicine at the University of California San Francisco, a member of the Varmus' Address to Helen Diller Family Comprehensive Cancer Center, and director of the Center for Tobacco Control Research and Education. The NCI Board of (Continued to page 2) Scientific Advisors Sequestration . Page 7 Federal Budget Cuts Enacted March 1; HHS Agencies Grapple with Consequences BSA Approves RFA By Matthew Bin Han Ong Reissuance for the The across-the-board 5.1 percent budget cuts that went into effect March Pediatric Brain 1 slash the NIH budget by $1.553 billion and the NCI budget by $219 million for the remaining fiscal year, officials say. -
Molecular Profile of Tumor-Specific CD8+ T Cell Hypofunction in a Transplantable Murine Cancer Model
Downloaded from http://www.jimmunol.org/ by guest on September 25, 2021 T + is online at: average * The Journal of Immunology , 34 of which you can access for free at: 2016; 197:1477-1488; Prepublished online 1 July from submission to initial decision 4 weeks from acceptance to publication 2016; doi: 10.4049/jimmunol.1600589 http://www.jimmunol.org/content/197/4/1477 Molecular Profile of Tumor-Specific CD8 Cell Hypofunction in a Transplantable Murine Cancer Model Katherine A. Waugh, Sonia M. Leach, Brandon L. Moore, Tullia C. Bruno, Jonathan D. Buhrman and Jill E. Slansky J Immunol cites 95 articles Submit online. Every submission reviewed by practicing scientists ? is published twice each month by Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts http://jimmunol.org/subscription Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html http://www.jimmunol.org/content/suppl/2016/07/01/jimmunol.160058 9.DCSupplemental This article http://www.jimmunol.org/content/197/4/1477.full#ref-list-1 Information about subscribing to The JI No Triage! Fast Publication! Rapid Reviews! 30 days* Why • • • Material References Permissions Email Alerts Subscription Supplementary The Journal of Immunology The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2016 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. This information is current as of September 25, 2021. The Journal of Immunology Molecular Profile of Tumor-Specific CD8+ T Cell Hypofunction in a Transplantable Murine Cancer Model Katherine A. -
The Histone Methyltransferase DOT1L Prevents Antigen-Independent
bioRxiv preprint doi: https://doi.org/10.1101/826255; this version posted November 18, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. The histone methyltransferase DOT1L prevents antigen-independent differentiation and safeguards epigenetic identity of CD8+ T cells Eliza Mari Kwesi-Maliepaard1*, Muhammad Assad Aslam2,3*, Mir Farshid Alemdehy2*, Teun van den Brand4, Chelsea McLean1, Hanneke Vlaming1, Tibor van Welsem1, Tessy Korthout1, Cesare Lancini1, Sjoerd Hendriks1, Tomasz Ahrends5, Dieke van Dinther6, Joke M.M. den Haan6, Jannie Borst5, Elzo de Wit4, Fred van Leeuwen1,7,#, and Heinz Jacobs2,# 1Division of Gene Regulation, Netherlands Cancer Institute, 1066CX Amsterdam, The Netherlands 2Division of Tumor Biology & Immunology, Netherlands Cancer Institute, 1066CX Amsterdam, The Netherlands 3Institute of Molecular Biology and Biotechnology, Bahauddin Zakariya University, 60800 Multan, Pakistan 4Division of Gene Regulation, Netherlands Cancer Institute, 1066CX Amsterdam, and Oncode Institute, The Netherlands 5Division of Tumor Biology & Immunology, Netherlands Cancer Institute, 1066CX Amsterdam, and Oncode Institute, The Netherlands 6Department of Molecular Cell Biology and Immunology, Amsterdam UMC, Location VUmc, 1081HV Amsterdam, The Netherlands 7Department of Medical Biology, Amsterdam UMC, location AMC, UvA, 1105 AZ Amsterdam, The Netherlands * These authors contributed equally to this work. # Equal contribution and corresponding authors [email protected]; [email protected] Lead contact: Fred van Leeuwen 1 bioRxiv preprint doi: https://doi.org/10.1101/826255; this version posted November 18, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. -
Amy Elizabeth Herr
Amy E. Herr, Ph.D. John D. & Catherine T. MacArthur Professor Bioengineering, University of California, Berkeley UNIVERSITY OF CALIFORNIA, Berkeley, CA 94720 BERKELEY [email protected] | herrlab.berkeley.edu EDUCATION 01/98 – 09/02 STANFORD UNIVERSITY Stanford, CA Doctor of Philosophy, Mechanical Engineering National Science Foundation Graduate Research Fellow “Isoelectric Focusing for Multi-Dimensional Separations in Microfluidic Devices” Advisors: Profs. Thomas W. Kenny & Juan G. Santiago 09/97 – 01/99 STANFORD UNIVERSITY Stanford, CA Master of Science, Mechanical Engineering National Science Foundation Graduate Research Fellow 09/93 – 06/97 CALIFORNIA INSTITUTE OF TECHNOLOGY (CALTECH) Pasadena, CA Bachelor of Science, Engineering & Applied Science with Honors APPOINTMENTS 07/19 – now JOHN D. & CATHERINE T. MACARTHUR PROFESSOR, UNIVERSITY OF CALIFORNIA, BERKELEY 07/14 – 07/19 LESTER JOHN & LYNNE DEWAR LLOYD DISTINGUISHED PROFESSOR (5-year appointment), UC BERKELEY 07/12 – 07/15 ASSOCIATE PROFESSOR, BIOENGINEERING, UNIVERSITY OF CALIFORNIA, BERKELEY 07/07 – 07/12 ASSISTANT PROFESSOR, BIOENGINEERING, UNIVERSITY OF CALIFORNIA, BERKELEY UC BERKELEY/UCSF GRADUATE GROUP IN BIOENGINEERING Directing a research group focused on design and study of microanalytical tools and methods that exploit scale-dependent physics & chemistry to address questions in the biosciences and biomedicine. Chan Zuckerberg Biohub Investigator (2017-21), National Advisory Council for Biomedical Imaging and Bioengineering (2020-23), Faculty Director of Bakar Faculty Fellows Program (2016-now), Co-Convener of Chancellor’s Advisory Committee on Life Sciences (2019-22), BioE Vice-chair for Engagement (2016- now), Director’s Council for Jacobs Institute of Design Innovation, Board Member of Chemical & Biological Microsystems Society (2013-19; Awards Chair 2016-18), Director of Bioengineering Immersion Experience (2012-22; NIH R25). -
Figure S17 Figure S16
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3D Genome Analysis Identifies Enhancer Hijacking Mechanism for High-Risk 2 Factors in Human T-Lineage Acute Lymphoblastic Leukemia
bioRxiv preprint doi: https://doi.org/10.1101/2020.03.11.988279; this version posted March 12, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. 1 3D Genome Analysis Identifies Enhancer Hijacking Mechanism for High-Risk 2 Factors in Human T-Lineage Acute Lymphoblastic Leukemia 3 Lu Yang1,2,3^, Fengling Chen4^, Haichuan Zhu1,2,3^§, Yang Chen4, Bingjie Dong1,2,3, 4 Minglei Shi4, Weitao Wang1,2,3, Qian Jiang6, Leping Zhang7, Xiaojun Huang2,6*, 5 Michael Q. Zhang4,5,8* and Hong Wu1,2,3,6* 6 7 1The MOE Key Laboratory of Cell Proliferation and Differentiation, School of Life 8 Sciences, 2Peking-Tsinghua Center for Life Sciences and 3Beijing Advanced 9 Innovation Center for Genomics, Peking University, Beijing 100871, China; 4MOE Key 10 Laboratory of Bioinformatics, Center for Synthetic and Systems Biology, 11 Bioinformatics Division, BNRist, Department of Automation, 5School of Medicine, 12 Tsinghua University, Beijing 100084, China; 6Peking University Institute of Hematology, 13 National Clinical Research Center for Hematologic Disease, 7Department of Pediatric 14 Hematology/Oncology, Peking University People’s Hospital, Beijing 100044, China; 15 8Department of Biological Sciences, Center for Systems Biology, The University of 16 Texas, Dallas 800 West Campbell Road, RL11, Richardson, TX 75080-3021, USA 17 18 ^ These authors contributed equally to this work. 19 §Current address: Institute of Biology and Medicine, College of Life and Health 20 Sciences, Wuhan University of Science and Technology, Hubei 430081, China. -
Patrick J. H. Bradley
(415) 734-2745 Patrick J. H. Bradley Gladstone Institutes, GIDB [email protected] 1650 Owens Street Pronouns: he/him/his Bioinformatics Fellow San Francisco, CA 94158 Current Position ······················································································· 2013— J. David Gladstone Institutes at UCSF Bioinformatics Fellow, Prof. Katherine S. Pollard Lab Academic History ····················································································· 2012—13 Lewis-Sigler Institute for Integrative Genomics, Princeton University Postdoctoral Fellow, Prof. Olga G. Troyanskaya Lab 2005—12 Dept. of Molecular Biology, Princeton University Ph.D. in Molecular Biology, Specialization in Quantitative and Computational Biology Thesis: Inferring Metabolic Regulation from High-Throughput Data Advisors: Prof. Joshua D. Rabinowitz, Prof. Olga G. Troyanskaya Committee: Prof. Ned S. Wingreen, Prof. David Botstein 2005 Dept. of Biology, Harvard College A.B. in Biology Peer-Reviewed Publications ·········································································· 1. Patrick H. Bradley, Katherine S. Pollard. “phylogenize: correcting for phylogeny reveals genes associated with microbial distributions.” Bioinformatics, 2019; btz722.∗;z 2. Patrick H. Bradley, Patrick A. Gibney, David Botstein, Olga G. Troyanskaya, Joshua D. Rabinowitz. “Minor isozymes tailor yeast metabolism to carbon availability.” mSystems, 2019; 4:e00170-18.∗;y 3. Patrick H. Bradley, Stephen Nayfach, Katherine S. Pollard. “Phylogeny-corrected identification -
Bcl11b and Combinatorial Resolution of Cell Fate in the T-Cell Gene
PAPER Bcl11b and combinatorial resolution of cell fate in the COLLOQUIUM T-cell gene regulatory network William J. R. Longabaugha,1,2, Weihua Zengb,1, Jingli A. Zhangc,3, Hiroyuki Hosokawac, Camden S. Jansenb, Long Lic,4,5, Maile Romero-Wolfc, Pentao Liud, Hao Yuan Kuehc,6, Ali Mortazavib,2, and Ellen V. Rothenbergc,2 aInstitute for Systems Biology, Seattle, WA 98109; bDepartment of Developmental and Cell Biology, University of California, Irvine, CA 92697; cDivision of Biology & Biological Engineering, California Institute of Technology, Pasadena, CA 91125; and dWellcome Trust Medical Research Council, Cambridge Stem Cell Institute, University of Cambridge, Cambridge CB2 1QR, United Kingdom Edited by Neil H. Shubin, The University of Chicago, Chicago, IL, and approved January 30, 2017 (received for review October 25, 2016) T-cell development from hematopoietic progenitors depends on The robust change in potential from DN2a to DN2b is also multiple transcription factors, mobilized and modulated by intra- accompanied by dynamic transcription factor expression changes thymic Notch signaling. Key aspects of T-cell specification network (8, 9) At least 20 regulatory genes have expression patterns that architecture have been illuminated through recent reports de- can be classed as “phase 1” (expressed in ETP and DN2a, then fining roles of transcription factors PU.1, GATA-3, and E2A, their down-regulated) or “phase 2” (turned on or significantly up- interactions with Notch signaling, and roles of Runx1, TCF-1, and regulated around commitment in DN2b) (5). To date, the most- Hes1, providing bases for a comprehensively updated model of the studied regulators of the phase 1 to phase 2 transition have been Notch signaling, GATA-3, TCF-1, and E2A, and PU.1 as a T-cell specification gene regulatory network presented herein. -
Genome-Wide Analyses Identify KLF4 As an Important Negative Regulator
Li et al. Molecular Cancer (2015) 14:26 DOI 10.1186/s12943-014-0285-x RESEARCH Open Access Genome-wide analyses identify KLF4 as an important negative regulator in T-cell acute lymphoblastic leukemia through directly inhibiting T-cell associated genes Wei Li1,2†, Zhiwu Jiang1,2†, Tianzhong Li1,2, Xinru Wei1,2,YiZheng1,2, Donghai Wu1,2, Lijian Yang3,4,ShaohuaChen3,4, Bing Xu5, Mei Zhong6,JueJiang7,YufengHu7,HexiuSu7, Minjie Zhang8,XiaojunHuang9,SuxiaGeng10, Jianyu Weng10,XinDu10,PentaoLiu11, Yangqiu Li3,4,HudanLiu7,YaoYao12* andPengLi1,2* Abstract Background: Kruppel-like factor 4 (KLF4) induces tumorigenesis or suppresses tumor growth in a tissue-dependent manner. However, the roles of KLF4 in hematological malignancies and the mechanisms of action are not fully understood. Methods: Inducible KLF4-overexpression Jurkat cell line combined with mouse models bearing cell-derived xenografts and primary T-cell acute lymphoblastic leukemia (T-ALL) cells from four patients were used to assess the functional role of KLF4 in T-ALL cells in vitro and in vivo. A genome-wide RNA-seq analysis was conducted to identify genes regulated by KLF4 in T-ALL cells. Chromatin immunoprecipitation (ChIP) PCR was used to determine direct binding sites of KLF4 in T-ALL cells. Results: Here we reveal that KLF4 induced apoptosis through the BCL2/BCLXL pathway in human T-ALL cell lines and primary T-ALL specimens. In consistence, mice engrafted with KLF4-overexpressing T-ALL cells exhibited prolonged survival. Interestingly, the KLF4-induced apoptosis in T-ALL cells was compromised in xenografts but the invasion capacity of KLF4-expressing T-ALL cells to hosts was dramatically dampened. -
Research Grants
RESEARCH GRANTS 1 HDF RESEARCH GRANTS We like the philosophy of the Hereditary Disease Foundation that monies raised go directly to support research and that scientists from around the world “are encouraged to collaborate and share their work. “ We’ve devoted ourselves to being supporters and research partners, and we have not been disappointed. The research is vibrant with possibilities. Sandy Fox Member, Board of Directors Hereditary Disease Foundation 1 HDF RESEARCH GRANTS Osama Al-Dalahmah, MD, DPhil Anna Pluciennik, PhD Columbia University, New York, NY Thomas Jefferson University, Philadelphia, PA Cheryl Arrowsmith, PhD Paul Ranum, PhD University of Toronto, Canada Children’s Hospital of Philadelphia, PA Anne Ast, PhD Piere Rodriguez-Aliaga, PhD Max Delbrück Center for Molecular Medicine Stanford University, Palo Alto, CA Berlin, Germany Jennie C. L. Roy, PhD Kristina Becanovic, PhD Massachusetts General Hospital Karolinska Institutet, Stockholm, Sweden Harvard Medical School, Boston, MA Abdellatif Benraiss, PhD David M. Sabatini, MD, PhD University of Rochester, Rochester, NY Whitehead Institute for Biomedical Research Massachusetts Institute of Technology, Cambridge, MA Veronica Ines Brito, PhD University of Barcelona Charlene Smith-Geater, PhD Instituto de Neurosciencias, Spain University of California, Irvine, CA Lauren Byrne, PhD Joan Steffan, PhD University College London (UCL), England University of California, Irvine, CA Amit Laxmikant Deshmukh, PhD Xiao Sun, PhD The Hospital for Sick Children, Toronto, Canada Southwestern Medical Center, Dallas, TX Steven Finkbeiner, MD, PhD Leslie Thompson, PhD Gladstone Institutes University of California, Irvine, CA University of California, San Francisco, CA Nicholas Todd, PhD Brent Fitzwalter, PhD Brigham and Women’s Hospital Broad Institute of MIT and Harvard, Cambridge, MA Harvard Medical School, Boston, MA Ali Khoshnan, PhD Ray Truant, PhD California Institute of Technology, Pasadena, CA McMaster University, Ontario, Canada Ryan Lim, PhD Jean Paul G. -
Engineered Type 1 Regulatory T Cells Designed for Clinical Use Kill Primary
ARTICLE Acute Myeloid Leukemia Engineered type 1 regulatory T cells designed Ferrata Storti Foundation for clinical use kill primary pediatric acute myeloid leukemia cells Brandon Cieniewicz,1* Molly Javier Uyeda,1,2* Ping (Pauline) Chen,1 Ece Canan Sayitoglu,1 Jeffrey Mao-Hwa Liu,1 Grazia Andolfi,3 Katharine Greenthal,1 Alice Bertaina,1,4 Silvia Gregori,3 Rosa Bacchetta,1,4 Norman James Lacayo,1 Alma-Martina Cepika1,4# and Maria Grazia Roncarolo1,2,4# Haematologica 2021 Volume 106(10):2588-2597 1Department of Pediatrics, Division of Stem Cell Transplantation and Regenerative Medicine, Stanford School of Medicine, Stanford, CA, USA; 2Stanford Institute for Stem Cell Biology and Regenerative Medicine, Stanford School of Medicine, Stanford, CA, USA; 3San Raffaele Telethon Institute for Gene Therapy, Milan, Italy and 4Center for Definitive and Curative Medicine, Stanford School of Medicine, Stanford, CA, USA *BC and MJU contributed equally as co-first authors #AMC and MGR contributed equally as co-senior authors ABSTRACT ype 1 regulatory (Tr1) T cells induced by enforced expression of interleukin-10 (LV-10) are being developed as a novel treatment for Tchemotherapy-resistant myeloid leukemias. In vivo, LV-10 cells do not cause graft-versus-host disease while mediating graft-versus-leukemia effect against adult acute myeloid leukemia (AML). Since pediatric AML (pAML) and adult AML are different on a genetic and epigenetic level, we investigate herein whether LV-10 cells also efficiently kill pAML cells. We show that the majority of primary pAML are killed by LV-10 cells, with different levels of sensitivity to killing. Transcriptionally, pAML sensitive to LV-10 killing expressed a myeloid maturation signature.