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Monica Justice

Monica J. Justice

E-mail: mjustice@bcm.edu

Professor, Baylor College of Medicine

B.S., Fort Hays State University, KS, 1977
Ph.D., Kansas State University, 1987
Postdoc, NCI, Frederick Cancer Research and Development Center, MD, 1988-92

Mammalian developmental genetics and models of human disease

My research uses mouse genetics and genomics to assign functions to mammalian genes by exploiting the fact that genes and whole chromosome regions are conserved between the mouse and human. Overall, my research aims to merge mouse modeling with clinical genetics to understand the basis for many human diseases, and to use these mouse models to ameliorate disease states. Our current research questions are:

  1. How do perturbations of gene expression lead to the development of hematopoietic cancers? We developed a tumor bank from lymphoid leukemias and lymphomas that were caused by the insertion of murine leukemia retroviruses, which provide a molecular tag for the gene altered, to discover many new proto-oncogenes that cause lymphoid disease. Most are involved in the initiation of the leukemia or lymphoma, and act by altering a progenitor cell. We also use mouse strains with germline mutations to study hemato-vascular development and genes that predispose to hematopoietic cancers. We collaborate with clinicians at Texas Children's Hospital to better understand the genetics of initiation, development and relapse of childhood ALL.
  2. Can therapeutic targets to ameliorate disease be identified through genetic modifier screens in mice? We chose as our model a mouse mutant that eliminates function of methyl CpG binding protein 2 (Mecp2), the gene mutated in 80 percent of the cases of Rett Syndrome (RTT), which is a severe neurological disease with autistic features and developmental regression. In a forward genetic dominant screen, we randomly mutate a second genomic site in Mecp2-mutant mice to identify genes that suppress symptoms. In a preliminary screen, we have identified five lines carrying inherited suppressors that increase lifespan and decrease other RTT-related symptoms. The mutations are identified by a combination of traditional mapping and exome capture followed by new high-throughput sequencing methods to determine the molecular cause of the phenotype. As expected, the majority of the genes act at the level of chromatin remodeling, but one reveals a non-CNS "systems" component to disease pathology. Our ultimate goal is to identify pharmacologically targetable alternatives that may ameliorate symptoms.
  3. What are the functions of mammalian genes? In the past, we used random forward mutagenesis to isolate over 500 mutant lines of mice with a variety of phenotypes relevant to human disease: cardiovascular, skeletal, hematopoietic, neurological, urogenital, skin/coat, and metabolic defects. We use large-scale high throughput sequencing to identify the lesions. These studies reveal that the vast majority of mammalian genes do not have assigned functions. Although we supply mutations throughout the world, my lab studies mutations with developmental phenotypes that affect multiple organ systems, such as the hematopoietic system, bone patterning and cardiovascular development. Our ultimate goal is to establish mouse models of human disease, and to understand pathways of gene function during development.

Selected Publications

Kile BT, Hentges KE, Clark AT, 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 425:81-86.

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. Developmental Cell 6:423-435.

Lorenzetti D, Bishop CE, Justice MJ (2004) Deletion of the Parkin coregulated gene causes male sterility in the quaking(viable) mouse mutant. Proceedings of the National Academy of Sciences USA 101:8402-8407.

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.

Lossie AC, Nakamura H, Thomas SE, Justice MJ (2005) Mutation of l7Rn3 shows that Odz4 is required for mouse gastrulation. Genetics 169:285-299.

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

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.

Dettman EJ, Justice MJ (2008) The zinc finger SET domain gene Prdm14 is overexpressed in lymphoblastic lymphomas with retroviral insertions at Evi32. PLoS ONE 3:e3823.

Boles MK, Wilkinson BM, Wilming LG, Liu B, Probst FJ, Harrow J, Grafham D, Hentges KE, Woodward LP, Maxwell A, Mitchell K, Risley MD, Johnson R, Hirschi K, Lupski JR, Funato Y, Miki H, Marin-Garcia P, Matthews L, Coffey AJ, Parker A, Hubbard TJ, Rogers J, Bradley A, Adams DJ, Justice MJ (2009) Discovery of candidate disease genes in ENU-induced mouse mutants by large-scale sequencing, including a splice-site mutation in nucleoredoxin. PLoS Genetics 5:e1000759.

Boles MK, Wilkinson BM, Maxwell A, Lai L, Mills AA, Nishijima I, Salinger AP, Moskowitz I, Hirschi KK, Liu B, Bradley A, Justice MJ (2009) A mouse chromosome 4 balancer ENU-mutagenesis screen isolates eleven lethal lines. BMC Genetics 10:12.

Dettman EJ, Simko SJ, Ayanga B, Carofino BL, Margolin JF, Morse HC, 3rd, Justice MJ (2011) Prdm14 initiates lymphoblastic leukemia after expanding a population of cells resembling common lymphoid progenitors. Oncogene 30:2859-2873.

Contact Information

Monica J. Justice, Ph.D.
Department of Molecular and Human Genetics
Baylor College of Medicine
One Baylor Plaza R804
Houston, Texas 77030, U.S.A.

Tel: (713) 798-5440
Fax: (713) 798-5386
E-mail: mjustice@bcm.edu

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