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Personal History
Education
• Amherst College, Amherst, MA: BA (magna cum laude), Biology/Independent Study, 1970
• Harvard Medical School, Boston, MA: MD, (cum laude), Medicine, 1974
• Children’s Hospital Medical Center, Boston, MA: Resident, Pediatric Intern & Resident, 1974-76
• National Cancer Institute, Bethesda, MD: Clinical Associate, 1978
• Amherst College, Amherst, MA: ScD (honorary), Biomedicine, 2001
Employment History
• 1978-1979: Investigator, Pediatric Oncology Branch, National Cancer Institute
• 1979-1984: Assistant Professor, Oncology & Pediatrics, Johns Hopkins University School of Medicine
• 1984-1993: Associate Professor, Oncology & Pediatrics, JHUSM
• 1984-2000: Director, Pediatric Oncology Division, JHUSM
• 1994-2009: Professor, Oncology & Pediatrics, JHUSM (Adjunct Professor 2009-present)
• 2000-2009: Co-Director, Immunology & Hematopoiesis Division, JHUSM
• 2009-present: Associate Dean for Research, Director of the Center for Stem Cell Biology & Regenerative Medicine, and Professor of Pediatrics; University of Maryland School of Medicine
Honors
• National Merit Finalist; Westinghouse & Ford Foundation Science Awards (honorable mention); National Honor Society & American Legion Scholarships
• Amherst College: Oscar E. Schotte Award, Magna cum Laude, Phi Beta Kappa, Sigma XI
• Harvard Medical School: Soma Weiss Award, cum Laude
• Junior Clinical Faculty Fellow, American Cancer Society
• Scholar Award, Leukemia Society of America
• Dr. Frederick Stohlman Award, Leukemia Society of America
• American Society for Clinical Investigation (Young Turks)
• King Fahd Chair in Pediatric Oncology, JHUSM
• The Kantor Family Prize for Cancer Research Excellence
• National Inventor of the Year Award, Intellectual Property Owners Association
• Hope Award, Leukemia Society of America, MD Chapter (award for extraordinary achievement)
• Herman and Walter Samuelson Chair in Cancer Research, JHUSM
• Innovator of the Year, Leukemia & Lymphoma Society of Maryland
• NFCR Fellow Award, National Foundation for Cancer Research
• Member, Subcommittee D (Translational Studies), National Cancer Inst Initial Review Group
• Return of the Child Award, Leukemia & Lymphoma Society of America (LLS’s highest honor)
• Chair, Career Development Program, Clinical Scholar & Fellow Awards, Leukemia & Lymphoma Society
• Member, National Cancer Institute Board of Scientific Advisors (BSA)
• David G. Marsh Genetics of Asthma and Allergic Diseases Award Lecture
• Member, National Cancer Institute Clinical Trials Advisory Committee (CTAC)
• American Association of Blood Banks’ Karl Landsteiner Memorial Award & Lectureship
Ongoing Research Support:
NIH/NCI P01CA70970
Sharkis (PI)
6/30/98-1/31/13
Hematopoietic Stem Cells for Transplantation
Role: PPG Co-PI; Project 4 Leader
Note: This PPG remains at Johns Hopkins University (JHU). Upon Dr. Civin’s move to the University of Maryland School of Medicine (UMB) in Feb. 2009, Dr. Saul Sharkis (formally co-PI) became PI and Dr. Civin became co-PI of this PPG. Dr. Civin’s Project 4 and effort component of Core A moved to UMB, as a subcontract from JHU.
Summary: The major goals of this Program Project Grant (PPG) are to better understand the pathophysiology of normal hematopoietic stem cells (HSCs) and abnormal HSCs in human diseases. Dr. Civin leads Project 4 entitled MicroRNA targeting of normal and leukemia stem-progenitor cells. The goals of Project 4 are to (1) quantify microRNA and mRNA expression in acute myeloid leukemia (AML) and acute lymphoid leukemia (ALL) stem cells vs the bulk population of AML and ALL blast cells, respectively, to predict which microRNAs may control leukemia stem cells (LSCs), and (2) determine the cellular and molecular mechanisms by which selected microRNAs affect the biology of LSCs vs the bulk AML and ALL cells. Core A provides central leadership, administrative management, and mentoring.
2007-MSCRFII-0114 (Maryland Stem Cell Research Fund/TEDCO)
Civin (PI)
10/1/07-9/30/10
MicroRNA Regulation of Adult and Embryonic Human Hematopoietic Development
Summary: The goals of this project are to (1) expand our microRNA profiling to highly purified subsets of primary adult human hematopoietic stem-progenitor cells (HSPCs) and human embryonic stem cell (hESC)-derived embryonic hematopoietic cells, (2) to determine the stages of hematopoiesis at which mir-155 blocks normal hematopoiesis, and (3) study the functional effects and molecular mechanism of mir-155 on embryonic hematopoiesis generated from hESCs.
NIH/NIDDK R01DK080750
Civin (PI)
5/1/08-4/30/11
MicroRNAs regulating erythroid development
Summary: The goals of this project are to extensively profile microRNA expression during the early stages of human and mouse erythropoiesis. We will determine if selected erythroid-expressed microRNAs (“E-microRNAs”) functionally affect erythropoiesis. Using erythroid cell lines and primary cells, we will then identify proteins whose synthesis is inhibited by each E-microRNA that affects erythropoiesis. Identifying the molecular mechanisms of the erythropoietic effects of these E-microRNAs may lead to novel means to expand and control erythroid development
2009-MSCRFE-0070-00 (Maryland Stem Cell Research Fund/TEDCO)
Civin (PI)
6/1/09-5/31/11
The Hippo Pathway in Control of Hematopoietic Organ Size and Stemness
Summary: The goals of this project are to: (1) determine whether gain-of-function of YAP promotes hematopoietic expansion; (2) profile the expression levels of the Hippo pathway genes across the human hematopoietic system; and (3) examine whether loss-of-function of YAP reduces HSC self-renewal capacity and/or inhibits hematopoietic lineage differentiation.
LLS 2007 Translational Grant 6082-08 (Leukemia & Lymphoma Society)
Civin (PI)
10/1/07-09/30/10
CD22 Immunotoxins for Acute Lymphoblastic Leukemia
Summary: The goal of this project is to translationally develop CD22 immunotoxins for B-precursor ALL by (1) preclinically assessing the efficacy of the “HA22” CD22 immunotoxin against the ALL stem cell, and (2) preclinically exploring potential synergies of HA22 with other agents as promising approaches to human Phase II clinical trials ongoing at NCI.
No ## (Samuel Waxman Cancer Research Foundation)
Civin (PI)
7/1/07-6/30/10
MicroRNAs regulating acute leukemias
Summary: The goal of this project is to elucidate the effects of selected hematopoietic stem-progenitor cell (HSPC)-expressed microRNAs, especially mir-155, on human leukemia stem cells (LSCs) and to determine the molecular mechanisms of these cellular microRNA effects.
No ## (National Foundation for Cancer Research)
Civin (PI)
10/1/03-9/30/13
NFCR Fellow Award
This award supports general laboratory infrastructure and specific research that is not specifically funded by any other source.
2007-MSCRFII-0090 (Maryland Stem Cell Research Fund/TEDCO)
Zambidis (PI)
10/1/07-9/30/10
Human Embryonic Stem Cell Models of Normal and Leukemic HSC
Role: Investigator
Summary: Dr. Zambidis’ goals in this project are to expand the novel human embryonic stem cell (hESC)-based hematopoietic models and extend these models toward studying the detailed developmental origins of normal and leukemic human HSCs.
Note: This is a grant to JHU. Dr. Civin receives effort support as a subcontract from JHU to UMB.
NIH/NIGMS R01GM077291
Chandrasegaran (PI)
8/1/07-7/31/12
Developing ZFNs as Molecular Tools for Targeted Integration
Role: Investigator
Summary: Dr. Chandrasegaran’s goal in this project is to develop zinc-finger nucleases as reagents for site-specific modification of mammalian cells including human cells
Note: This is a grant to JHU. Dr. Civin receives effort support as a subcontract from JHU to UMB.
NIH/NIDDK R01DK082722
Roy (PI)
09/15/09-08/31/14
Anemia of Inflammation and of Chronic Diseases
Role: Investigator
Summary: Dr. Roy’s aims in this project are to: (1) determine whether hepcidin antimicrobial peptide or IL-6 is required for the anemia of inflammation and chronic diseases (AICD) or the anemia associated with aging; (2) determine whether genes required for hemoglobin synthesis and erythroid maturation are inhibited by inflammation and aging; and (3) validate IL-6-mediated inhibition of hemoglobin synthesis and erythroid maturation in vitro. Dr. Civin will advise in the analysis of erythroid populations in AICD mice and in the analysis of gene expression data in erythroid precursors.
Note: This is a grant to JHU. Dr. Civin receives effort support as a subcontract from JHU to UMB.
NIH/NHLBI RC2 HL101582
Cheng (PI)
09/30/09-9/29/11
Characterizing Blood Progenitor Cells Differentiated from Human iPS and ES Cells
Role: Investigator
Summary: Grand Opportunities (GO) grant, ARRA Stimulus: The subcontract to the Civin lab from this grant will focus first on comparing correlated mRNA and microRNA expression in human hematopoietic stem-progenitor cells and erythroid progeny derived from adult bone marrow vs from induced pluripotent stem (iPS) cells or human embryonic stem (hES) cells. These results will then be compared with different bioinformatic/statistical analyses of the same data and then also correlated with methylomics and functional results, in collaboration with the JHU team.
Note: This is a grant to JHU. Dr. Civin’s lab research support is provided via a subcontract from JHU to UMB.
Publications
SELECTED PEER-REVIEWED PUBLICATIONS (from >170 peer-reviewed articles):
Cui Y, Kelleher E, Straley E, Fuchs E, Gorski K, Levitsky H, Borrello I, Civin CI, Schoenberger S, Cheng L, Pardoll DM, and Whartenby KA. Immunotherapy of established tumor using bone marrow transplant with antigen-gene modified hematopoietic stem cells. Nat Med 2003;9:952-958.
Angelopoulou M, Novelli E, Grove JE, Rinder HM, Civin C, Cheng L, and Krause DS. Cotransplantation of human mesenchymal stem cells enhances human myelopoiesis and megakaryocytopoiesis in NOD/SCID mice. Exp Hematol 2003;31:413-420.
Dunlap S, Yu X, Cheng L, Civin CI, and Alani RM. High-efficient stable gene transduction in primary human melanocytes using a lentiviral expression system. J Invest Dermatol 2004;122:549-551.
Matsui W, Huff CA, Wang Q, Malehorn MT, Barber J, Tanhehco Y, Smith BD, Civin CI, and Jones RJ. Characterization of clonogenic myeloma cells. Blood 2004;103:2332-2336.
Georgantas RW, Tanavde V, Malehorn M, Heimfeld S, Chen C, Carr L, Murillo F, Riggins G, and Civin CI. Microarray and SAGE analyses identify known and novel transcripts over-expressed in hematopoietic stem cells. Cancer Res 2004;64:4434-4441.
Lewis JD, Amin S, Civin CI, Lietman PS. Ex vivo zidovudine (AZT) treatment of CD34+ bone marrow progenitors causes decreased steady state mitochonidrial DNA (mtDNA) and increased lactate production. Hum Exp Toxicol 2004;23:173-185.
Esni F, Ghosh B, Biankin AV, Lin JW, Albert MA, Yu X, MacDonald RJ, Civin CI, Real FX, Pack MS, Ball DW, Leach SD. Notch inhibits Ptf1 function and acinar cell differentiation in developing mouse and zebrafish pancreas. Develop 2004;131:4213-4224.
Topaloglu O, Civin CI, Bunz F. Digital HLA allelotyping. Cancer Biol 2004;3:899-902.
D'Costa J, Chaudhuri S, Civin CI, Friedman AD. CBFbeta-SMMHC slows proliferation of primary murine and human myeloid progenitors. Leukemia 2005;19:921-929.
Zambidis ET, Peault B, Park TS, Bunz F, Civin CI. Hematopoietic differentiation of human embryonic stem cells progresses through sequential hemato-endothelial, primitive, and definitive stages resembling human yolk sac development. Blood 2005;206:860-870.
Ravindranath Y, Chang M, Steuber CP, Becton D, Dahl G, Civin C, Camitta B, Carroll A, Raimondi SC, Weinstein HJ. Pediatric Oncology Group (POG) studies of acute myeloid leukemia (AML): a review of four consecutive childhood AML trials conducted between 1981 and 2000. Leukemia 2005;19:2101-2116.
Bala P, Georgantas RW 3rd, Sudhir D, Suresh M, Shanker K, Vrushabendra BM, Civin CI, Pandey A. TAGmapper: A web-based tool for mapping SAGE tags. Gene 2005;364:123-129.
Topaloglu O, Hurley PJ, Yildirim O, Civin CI, Bunz F. Improved methods for the generation of human gene knockout and knockin cell lines. Nucleic Acids Res 2005;33:e158.
Yu X, Alder JK, Chun JH, Friedman AD, Heimfeld S, Cheng L, Civin CI. HES1 inhibits cycling of hematopoietic progenitor cells via DNA binding. Stem Cells 2006;24:876-888.
Wang D, D’Costa J, Civin CI, Friedman AD. C-EBP{alpha} directs monocytic commitment of primary myeloid progenitors. Blood 2006;108:1223-1229.
Zhang L, D’Costa J, Kummalue T, Civin CI, Friedman AD. Identification of a region on the outer surface of the CBFβ-SMMHC myeloid oncoprotein assembly competence domain critical for multimerization. Oncogene 2006;25:7289-7296.
Georgantas RW, 3rd, Bohana-Kashtan O, Civin C. Ex vivo soluble Fas ligand treatment of donor cells to selectively reduce murine acute graft versus host disease. Transplantation 2006;82:471-478.
Georgantas RW, 3rd, Hildreth R, Morisot S, Alder J, Liu CG, Heimfeld S, Calin GA, Croce CM, Civin CI. CD34+ hematopoietic stem-progenitor cell microRNA expression and function. A circuit diagram of differentiation control. Proc. Natl. Acad. Sci. 2007;104:2750-2755.
Alder JK, Georgantas RW, Hildreth RL, Kaplan IM, Morisot S, Yu X, McDevitt M, Civin CI. Kruppel-like factor 4 is essential for inflammatory monocyte differentiation in vivo. J Immunology 2008; 180:5645-5652.
Yu X, Zou J, Ye Z, Hammond H, Chen G, Tokunaga A, Mali P, Li Y-M, Civin C, Gaiano N, Cheng L. Notch signaling activation in human embryonic stem cells is required for embryonic but not trophoblastic lineage commitment. Cell Stem Cell 2008; 1:461-471.