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.