Cancer Institute

  • Joseph Maher

    maher_joseph.jpgProfessor, Department of Medicine
    Cancer Genetics Program
    MD, UT Southwestern Medical School, Dallas, TX
    Internal Medicine (internship/residency), UT Southwestern Medical School, Dallas
    Medical Genetics (fellowship), Johns Hopkins University School of Medicine, Baltimore, MD
    Postdoc - Molecular Biology & Genetics, Johns Hopkins University School of Medicine, Baltimore

    Contact information
    Guyton Research Bldg., room G658
    University of Mississippi Medical Center
    2500 N. State St.
    Jackson, MS 29216
    E-mail: jmaher@umc.edu 

    Research interests

    • Cell-fate determination in development, metabolism, and cancer cell biology
    • Fem1 genes in cell differentiation, transformation, and apoptosis regulation
    • Clinical cancer genetics

    Research synopsis

    Our laboratory is interested in the role of cell-fate determination in development, homeostasis, and cancer cell transformation; and the associated signaling, transcriptional, and post-transcriptional mechanisms that govern these processes. We focus the Fem1 genes (Fem1a, Fem1b, Fem1c), homologs of the fem-1 gene in the sex-determination pathway of the nematode C. elegans; this pathway in the nematode is a signal transduction/transcriptional regulatory pathway that controls diverse cell-fate decisions, including apoptosis, and has homology to the Hedgehog signaling pathway of flies and mammals.

    Fem1b is pro-apoptotic and has been found to be a Wnt and c-Myc target gene in neoplastic intestinal epithelium, and mediates proteasome inhibitor-induced apoptosis of malignant colon cancer cells. Currently we are exploring: the molecular basis of Fem1b regulation in colon cancer cells; the involvement of Fem1b in other epithelial cancers; the interaction of Fem1b with the Gli oncogenes; we are also exploring the utility of Fem1b expression as a biomarker of pathological Wnt signaling in neoplastic epithelium. Fem1a interacts with NF-κB, and we are investigating this interaction in skeletal muscle differentiation and rhabdomyosarcoma development.

    In addition, I have a clinical interest in patients with genetic disorders, including hereditary predisposition to cancer, which offers opportunities for patient-oriented research into cancer gene discovery and clinical utility.

    Selected publications

    • Subauste, M.C., Sansom, O.J., Porecha, N., Raich, N., Du, L., and Maher, J.F. Fem1b, a pro-apoptotic protein, mediates proteasome inhibitor-induced apoptosis of human colon cancer cells. Molecular Carcinogenesis 49: 105-113 (2010).
    • Subauste, M.C., Ventura-Holman, T., Du, L., Subauste, J.S., Chan, S.-L., Yu, V.C., & Maher, J.F. RACK1 down-regulates levels of the pro-apoptotic protein Fem1b in apoptosis-resistant colon cancer cells. Cancer Biology & Therapy 8: 2295-2302 (2009).
    • Lu, D, Ventura-Holman, T., Li, J., McMurray, R.W., Subauste, J.S. & Maher, J.F. Abnormal Glucose Homeostasis and Pancreatic Islet Function in Mice with Inactivation of the Fem1b Gene. Molecular & Cellular Biology 25: 6570-6577 (2005).
    • Ventura-Holman, T., Seldin, M.F., Li, W., and Maher, J.F. The Murine Fem1 Gene Family: Homologs of the Caenorhabditis elegans Sex-Determination Protein FEM-1. Genomics 54: 221-230 (1998).
    • Maher,J.F., and Nathans,D. Multivalent DNA-Binding Properties of the HMG-I Proteins. Proceedings of the National Academy of Science 93: 6716-6720 (1996).