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Dr. Civin's Lab: Current Projects

Hematopoietic Stem Cells for Transplantation

The major goals of this project 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. Dr. Civin and his lab receive funding for Project 4 via a subcontract from JHU to UMB.

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/Mentor  

NFCR Fellow Award

To support general laboratory infrastructure and specific research that is not specifically funded by any other source.

Role: Principal Investigator  

MicroRNAs regulating acute leukemias

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 cellulars microRNA effects.

Role: Principal Investigator 

CD22 Immunotoxins for Acute Lymphoblastic Leukemia

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.

Role: Principal Investigator 

MicroRNA Regulation of Adult and Embryonic Human Hematopoietic Development

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) todetermine 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.

Role: Principal Investigator 

Human Embryonic Stem Cell Models of Normal and Leukemic HSC

The major goals of this project are to expand novel human embryonic stem cell (hESC)-based hematopoietic models, and now extend these models toward studying the detailed developmental origins of normal and leukemic human HSCs.

Role: Investigator 

NOTE: This is a grant to Johns Hopkins University (JHU). Since Dr. Civin’s move to UMB in Feb. 2009, Dr. Civin receives effort support as a subcontract from JHU to UMB. 

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 

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 

The Hippo Pathway in Control of Hematopoietic Organ Size and Stemness

The major 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.

Role: Principal Investigator