Medical College of Georgia
Department of Pathology
Medical College of Georgia
Department of Georgia Cancer Center
The Graduate School
Medical College of Georgia
Department of Neuroscience and Regenerative Medicine
Medical College of Georgia
Department of Biochemistry and Molecular Biology
Administration
Department of The Graduate School
Leadership Roles: Associate Director, basic sciences
Main Area of Research Focus of interest -
Genetic development of AML and Role of WASF3 in metastasis
Research projects in the Cowell Laboratory are aimed at improving our understanding of the molecular genetic basis of cancer. A broad range of cell and molecular biology, proteomics, genomics, protein chemistry and animal modeling techniques are used to dissect the genetic contribution to various aspects of cancer predisposition, development and progression in a variety of tissue types. Current specific areas are outlined below.
WAVE3 plays a central role in the promotion of invasion and metastasis through regulation of the actin cytoskeleton reorganization. Inactivation of WASF3 function, therefore, by whatever means, leads to loss of invasion regardless of the genetic background of the cells involved, making its suppression of broad potential application to suppressing metastasis. Highly stable, stapled peptides that target protein interactions between WASF3 and NCKAP1/CYFIP1 which suppression of invasion in vitro have been developed, and in vivo, the same peptides lead to suppression of metastasis using breast cancer cells as the model. Ongoing studies are designed to optimize thestapled peptides through medicinal chemistry approaches to improve their effectiveness and stability and to develop formulations for effective delivery in vivo.
A chimeric FGFR1 kinase is associated with a myeloproliferative disorder that progresses to AML through constitutive activation of the kinase domain. Using syngeneic mouse models of this disease the various fusion kinases lead to diseases identical to that seen in the comparable human diseases. Further, using CD34+ hemato-progenitor cells from cord blood, human cell models of FGFR1-driven AML have been developed in immunocompromised mice. These models have been used to investigate the use of FGFR1 inhibitor drugs as a means of treating this disease. Using genomics approaches, genetic changes seen in the various models support the idea of targeting different genetic abnormalities in the treatment of FGFR1 disease.
