Professor, Departments of Molecular and Human Genetics and Molecular Physiology and Biophysics; Programs in Developmental Biology, Cell & Molecular Biology, and Translational Biology and Molecular Medicine
Member, Dan L. Duncan Cancer Center
Associate Member, Center for Stem Cells and Regenerative Medicine

B.S., Fort Hays State University, 1977
Ph.D., Kansas State University, 1987
Postdoc, National Cancer Institute, Frederick Cancer Research and Development Center, 1992

RESEARCH INTERESTS:

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.

SELECTED PUBLICATIONS:

1. Castillo A, Morse HC 3rd, Godfrey VL, Naeem R, Justice MJ (2007). Overexpression of Eg5 causes genomic instability and tumor formation in mice. Cancer Res. 67: 10138-10147.

2. Kile BT, Panopoulos AD, Stirzaker RA, Hacking DF, Tahtamouni LH, Willson TA, Mielke LA, Henley KJ, Zhang JG, Wicks IP, Stevenson WS, Nurden P, Watowich SS, Justice MJ (2007). Mutations in the cofilin partner Aip1/Wdr1 cause autoinflammatory disease and macrothrombocytopenia. Blood 110: 2371-2380.

3. Zheng L, Baek HJ, Karsenty G, Justice MJ (2007). Filamin B represses chondrocyte hypertrophy in a Runx2/Smad3-dependent manner. J. Cell Biol. 178: 121-128.

4. Hentges KE, Pollock DD, Liu B, Justice MJ (2007). Regional Variation in the Density of Essential Genes in Mice. PLoS Genet. 3: e72 [Epub ahead of print].

5. Hentges KE, Weiser KC, Schountz T, Woodward LS, Morse HC, Justice MJ (2005). Evi3, a zinc-finger protein related to EBFAZ, regulates EBF activity in B-cell leukemia. Oncogene 24: 1220-1230.

6. Bialek P, Kern B, Yang X, Schrock M, Sosic D, Hong N, Wu H, Yu K, Ornitz DM, Olson EN, Justice MJ, Karsenty G (2004). A twist code determines the onset of osteoblast differentiation. Dev. Cell 6: 423-435.

7. George A, Morse HC III, Justice MJ (2003). The homeobox gene Hex induces T-cell-derived lymphomas when overexpressed in hematopoietic precursor cells. Oncogene 22: 6764-6773.

8. Kile BT, Hentges KE, Clark A, Nakamura H, Salinger AP, Liu B, Box N, Stockton DW, Johnson RL, Behringer RR, Bradley A, Justice MJ (2003). Functional genetic analysis of mouse Chromosome 11. Nature 485: 81-86.

For more publications, see listing on Pub Med.

CONTACT INFORMATION:

Monica Justice, Ph.D.
Department of Molecular and Human Genetics
Baylor College of Medicine
One Baylor Plaza
Houston, TX 77030, U.S.A.
Mail Stop: BCM225

Phone: 713-798-5440
Fax: 713-798-1445
E-mail:
Web site: http://www.mouse-genome.bcm.tmc.edu/labs/JusticeLabHome.asp

Back to top