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Genetics & Tumor Cell Biology



The Department of Genetics & Tumor Cell Biology studies the genetic and molecular basis of several human diseases; molecular mechanisms involved in early mouse development and organogenesis; and the roles of oncogenes, tumor suppressors, cell cycle regulators, and other governors of stress responses in cancer. Summaries describing the work of individual faculty members can be found under their names, as well as in the Molecular Oncology section of the annual report.

A central theme in the department is the use of mouse models to study gene function and to test gene and small molecule therapeutic strategies for cancer and metabolic diseases. Engineered animals are generated in the Transgenic/Gene Knock-out Facility. The department also maintains Cancer Center Core laboratories for Flow Cytometry and Cell Sorting, Cell Microinjection and Cytogenetics. Click on Shared Resources in Related Topics for more information.

Genetics
One of our laboratories is examining the role of specific recurrent chromosomal translocations in myeloid leukemias and solid tumors. Through detailed studies of the translocations, we have identified fusion genes encoding transcription factors that directly influence the growth of cancer cells. Other investigators study the consequences of gene defects associated with ataxia telangiectasia and lysosomal storage disorders. Using mouse models, one laboratory focuses on how mutations affecting DNA repair genes lead to cancer and neuronal degeneration in the brain. Another group studies the role of a 3-enzyme lysosomal complex involved in degradation of oligosaccharides and glycoproteins and the role of a specific ubiquitin ligase in muscle development. Two researchers investigate the functions of genes involved in pattern formation and organogenesis during early mouse development with particular focus to the pancreas, liver, lymphatic vasculature, and the visual system.

Tumor Cell Biology
Two laboratories are examining the roles of cyclin-dependent kinases, CDK inhibitors, and tumor suppressors in both mouse development and tumor formation.  Emphasis is placed on mouse models for particular tumor types – lymphomas, medulloblastomas, and vascular tumors – in which different oncogenes, tumor suppressors, and cell cycle regulators functionally interact to determine the rate and severity of tumor development. Others study how cell cycle regulators and transcription factors trigger checkpoint responses leading to either growth arrest or apoptosis in various biologic settings, including pediatric tumors such as neuroblastoma and lymphocytic leukemia.  One laboratory focuses on how cells resist formation of improperly folded proteins in the secretory compartment.  Another group studies the structures of ubiquitin and ubiquitin-like protein ligases that affect protein turnover and compartmentalization within cells.

The Department is chaired by Gerard Grosveld, PhD, and co-chaired by Charles J. Sherr, MD, PhD.

 

 


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