Associate Director for Basic Science
Leader of Molecular Oncology and Biomarkers Program
GRU Cancer Center
Professor of Pathology
Georgia Regents University
1410 Laney Walker Blvd., CN-2133
Augusta, GA 30912
John Kenneth Cowell, Ph.D. is the Associate Center Director for Basic Science and Leader of the Molecular Oncology Program at the GHSU Cancer Center. Dr. Cowell earned his Ph.D. (1979) and a D.Sc. (1993) from The University of Sheffield, United Kingdom. Dr. Cowell is a Professor in the Department of Pathology in the Medical College of Georgia at GHSU.
Dr. Cowell studies the molecular genetics of cancer using a variety of genomics and cell and molecular biology approaches. His research focus is on breast cancers and leukemias, and cancers in children.
Dr. Cowell has been characterizing the molecular changes in human cancers such as Wilms tumor, glioblastoma, medulloblastoma and leukemias using gene expression arrays, comparative genome hybridization, and Next Generation Sequencing. He is currently investigating the role of the WASF3 gene in the promotion of cancer metastasis using in vivo models in mice and zebrafish. Inactivation of the WASF3 gene leads to suppression of metastasis in a wide variety of cancer cell types, and its overexpression promotes invasion and metastasis. Using different model cell systems, WASF3 has been shown to function as a mediator of signaling from receptor kinases to the actin cytoskeleton and involves the RAS, PI3K, NFkB and AKT pathways. The requirement for WASF3 to promote metastasis offers an opportunity to develop small molecules to inhibit its function. The zebrafish model that defines metastasis in 3-day experiments provides a high throughput system to screen for these molecules.
The Cowell laboratory also analyzes the molecular etiology of Stem Cell Leukemia/Lymphoma (SCLL) syndrome, which is characterized by chromosome 8p11 translocations activating the FGFR1 kinase. Animal models have been developed by adoptive transfer of hematopoietic stem cells in syngeneic animals and of human CD34+ cord blood cells into NOD/SCID/IL2Rγ- (NSG) mice. SCLL models in mice develop a myeloproliferative disease (MPD) as well as T-lymphoma or B-lymphoma and acute myelogenous leukemia (AML), as in the human disease. In the NSG mice the disease is largely AML. This model provides an opportunity to determine the genetic events that cause the transition from MPD to AML. Understanding this transition process and structure has broad implications for the treatment and clinical management of SCLL disease. Through a detailed molecular characterization of the development of SCLL, specific genes have been identified such as Notch1, SRC, PI3K, BCL2, FLT3 and FGFR1, and targeting these proteins can effectively suppress leukemogenesis. The animal models also provide the opportunity to evaluate the efficacy of novel drugs in treating SCLL and AML.