John Cowell

Professor

John Cowell

Professor

Academic Appointment(s)

Medical College of Georgia
Department of Pathology

Medical College of Georgia
Department of Georgia Cancer Center

Medical College of Georgia
Department of Neuroscience and Regenerative Medicine

Medical College of Georgia
Department of Biochemistry and Molecular Biology

The Graduate School

Bio

Leadership Roles: Associate Director, basic sciences
Main Area of Research Focus of interest -
Genetic development of AML and Role of WASF3 in metastasis

  • (706) 721-4381
  • CN 2133

Education

  • DS, Genetics, General University of Sheffield The, 1993

  • Ph.D., Genetics, General University of Sheffield The, 1979

  • BS, Genetics, General University of Sheffield The, 1974

Courses Taught Most Recent Academic Year

  • CLSC 7990

    Clin Molecular Methds Intern

Scholarship

Selected Recent Publications

  • ) Inactivation of Lgi1 in murine neuronal precursor cells leads to dysregulation of axon guidance pathways, 2019
    Journal Article, Professional Journal
  • Critical individual roles of the BCR and FGFR1 kinase domains in BCR-FGFR1-driven stem cell leukemia/lymphoma syndrome, 2019
    Journal Article, Professional Journal
  • Distinct Signaling Programs associated with Progression of FGFR1 driven leukemia in a Mouse Model of Stem Cell Leukemia Lymphoma Syndrome, 2019
    Journal Article, Professional Journal
  • Epigenetic silencing of miR-150 by DNMT1 contributes to FGFR1 fusion kinase driven leukemogenesis, 2019
    Journal Article, Professional Journal
  • Loss of the BCR-FGFR1 GEF domain suppresses RhoA activation and enhances B-lymphomagenesis in mice, 2019
    Journal Article, Professional Journal

Research Interests

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.