Robert Wood Johnson Medical School
Department of Biochemistry & Molecular Biology
675 Hoes Lane
Piscataway, NJ 08854
Mammalian genetics. human diseases, developmental biology, obesity cancer
Our starting point was the mouse mutant, pygmy and we identified Hmga2 as the gene responsible for the mutation and demonstrated that the gene is expressed exclusively in the mesenchyme prior to its differentiation. Therefore, modulation of Hmga2 expression impacts both mesenchymal cell proliferation and differentiation and has led to the basis of the two main projects in our laboratory.
Our studies in obesity have demonstrated that the pygmy mice are intransigent to various obesity inducing stimuli. Taking advantage of the various genotypes at the Hmga2 locus under normal and obese conditions, we have identified by microarray analysis a number of genes which are expressed exclusively in the adipocyte and their expression is enhanced or repressed during obesity. Currently, we are deciphering the function and molecular pathways of these genes in adipogenesis with a focus on their potential for novel insights into the etiology and pathology of obesity.
The second major project arose from our studies which demonstrated that HMGA2 is at the translocation site of a number of human mesenchymal tumors. Recently, we have shown that HMGA2 is localized to the invasive front of epithelial tumors and ectopic expression of HMGA2 will induce epithelial cells to adopt a mesenchymal phenotype and become invasive. This has led to our hypothesis that there will be a number of genes, which are normally expressed in the mesenchyme, that will be required to induce epithelial cells to become metastatic. Currently, we are identifying the downstream target genes that are activated or repressed by HMGA2 in epithelial cells.