| Monica Justice, Ph.D.
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| Professor, Department of Molecular and Human Genetics
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Professor, Department of Molecular Physiology and Biophysics; Programs in Cell & Molecular Biology, Developmental Biology, and Translational Biology and Molecular Medicine
Member, Dan L. Duncan Cancer Center
Associate
Member, Center for Stem Cells and Regenerative Medicine
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B.S., Fort Hays State University, 1977
Ph.D., Kansas State University, 1987
Postdoc, National Cancer Institute, Frederick Cancer Research and Development Center, 1992
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My lab uses molecular genetic approaches to study hematopoiesis and hematopoietic cancers using powerful genetic systems in the mouse. Hematopoiesis is a complex process that involves progressive differentiation steps towards lineage commitment from a self-renewing stem cell. In mammals, differentiation of hematopoietic cells takes place in multiple sites and times during development: the fetal yolk sac and mesodermal aortic/gonadal region, the fetal liver, and the bone marrow.
In particular, we are interested in how perturbations of gene expression in somatic cells can lead to the development of hematopoietic cancers. To this end, we have developed a large tumor bank from leukemias and lymphomas that were caused by the insertion of murine leukemia retroviruses, which provide a molecular tag for the gene altered. We have used high-throughput techniques to identify genomic sequences flanking the retroviral insertions in the tumors. Using this resource, we have discovered many new proto-oncogenes that can cause lymphoid disease. The genetic profile of insertion sites identifies pathways that lead to the development of lymphoid disease, while they define important events in lymphoid cell differentiation. Our retrovirus-tagged lymphoid tumor bank represents the largest bank of mouse lymphoid (T- and B-cell) tumors available. One unique feature of the bank is that we saved single cell suspensions from the tumors to reconstitute primary tumor cells. Studies of the proto-oncogene in its normal milieu give insight into how altering the gene causes the development of leukemia. Of primary interest, we find that the majority of genes that we discover are involved in the initiation of the leukemia or lymphoma, and act by altering a progenitor cell. Collaborations are established to show that the gene is involved in human cancer. Our studies may lead to the development of therapeutic targets for cancer stem cells.
We also use mouse strains with germline mutations to study early hemato-vascular development and genes that predispose to hematopoietic cancers. The chemical N-ethyl-N-nitrosourea (ENU) is a powerful mouse mutagen for forward genetic phenotype-driven screens. Large-scale screens for developmental phenotypes must take into account the ease of recovering and maintaining mutations that are detrimental to the organism. We use engineered mouse balancer chromosomes in ENU mutagenesis screens designed to isolate recessive mutations with developmental defects. The phenotypes are relevant to human disease, causing cardiovascular, skeletal, hematopoietic, neurological, urogenital, skin/coat, and metabolic defects. My lab focuses on mutations with defects in hematopoiesis, many with defects in autoimmunity or inflammation. With every phenotyping tool in our hands, as well as molecular biology and biochemistry capabilities, our lab is uniquely equipped to study the wide range of developmental defects in the mutants. Our ultimate goal is to establish mouse models of human disease, and to understand pathways of gene function during development.
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