Curt I Civin
 

Curt I Civin M.D.

Academic Title: Professor
Primary Appointment: Pediatrics
Additional Title(s): Director of the Center for Stem Cell Biology & Regenerative Medicine; Associate Dean for Research
ccivin@som.umaryland.edu
Location: BRB, 14-021; HSF II, S103D (lab)
Phone: (410) 706-1198

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

Active Research Grants:

P01CA70970
Sharkis (PI)
6/30/98-1/31/13
NIH/NCI
Hematopoietic Stem Cells for Transplantation

The major goals of this Program Project are to better understand the pathophysiology of normal hematopoietic stem cells (HSCs) and abnormal HSCs in human diseases. Dr. Civin is budgeted to receive effort support and leads Project 4 entitled “MicroRNA targeting of normal and leukemia stem-progenitor cells”. The specific aims of Core A are to provide central leadership, administrative management, and mentoring. 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.
Role: Co- Principal Investigator


T32CA60441
Small (PI)
9/30/93-5/31/13
NIH/NCI
Lab Research Training in Pediatric Oncology-Hematology

The major goals of this project are to provide postdoctoral lab research training for MDs and PhDs on topics highly related to childhood cancer and blood diseases (10 slots/yr). C. Civin receives no salary support.
Role: Investigator


No number
Civin (PI)
10/1/03-9/30/13
National Foundation for Cancer Research
NFCR Fellow Award

This grant provides funds to support general laboratory infrastructure and specific research that is not specifically funded by any other source.
Role: Principal Investigator

No number
Civin (PI)
7/1/07-6/30/09
Samuel Waxman Cancer Research Foundation
MicroRNAs regulating acute leukemias

The major goals of this project are 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.
Role: Principal Investigator


LLS 2007 Translational Grant 6082-08
Civin (PI)
10/1/07-09/30/10
Leukemia & Lymphoma Society
CD22 Immunotoxins for Acute Lymphoblastic Leukemia

The major goals of this project are 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, (2) preclinically exploring potential synergies of HA22 with standard chemotherapeutic agents, and (3) advancing the most promising approaches to our human Phase II clinical trials. LLS Translational Grants may be competitively renewed for years 4-5 of funding, if there is a clinical trial ongoing (as there is in this case).
Role: Principal Investigator


2007-MSCRFII-0114
Civin (PI)
10/1/07-9/30/10
Maryland Stem Cell Research Fund
MicroRNA Regulation of Adult and Embryonic Human Hematopoietic Development

The major goals of this project are (1) to 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) to study the functional effects and molecular mechanism of mir-155 on embryonic hematopoiesis generated from hESCs. This project involves profiling normal primary and hESC-derived HSPC subsets. The ultimate goal of this Maryland Stem Cell Research Fund project is to extend our understanding of the developmental origin of hematopoiesis, and is not focused on erythropoiesis.
Role: Principal Investigator


2007-MSCRFII-0090
Zambidis (PI)
10/1/07-9/30/10
Maryland Stem Cell Research Fund
Human Embryonic Stem Cell Models of Normal and Leukemic HSC

The major goals of this project are to expand the novel human embryonic stem cell (hESC)-based hematopoietic model originally developed by this PI, and now extend toward studying the detailed developmental origins of normal and leukemic human HSCs.
Role: Investigator


2007-MSCRFE-0089
Chandrasegaran (PI)
10/1/07-9/30/09
Maryland Stem Cell Research Fund
Targeted Engineering of the Human Genome in Stem Cells

The major goal of this project is to develop zinc-finger nuclease technologies to genetically modify human adult or embryonic stem cells.
Role: Investigator


R01GM077291
Chandrasegaran (PI)
8/1/07-7/31/12
NIH/NIGMS
Developing ZFNs as Molecular Tools for Targeted Integration

The major goal of this project is to develop zinc-finger nucleases as reagents for site-specific modification of mammalian cells including human cells.
Role: Investigator 


R01DK080750
Civin (PI)
4/1/08-3/31/11
NIH/NIDDK
MicroRNAs regulating erythroid development

In this project, we seek 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 for research and potential clinical applications.
Role: Principal Investigator

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.




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