Department of Molecular Virology, Immunology & Medical Genetics
910 Biomedical Research Tower
460 W 12th Ave
Columbus , OH 43210
Phone: (614) 688-3137
Fax: (614) 688-8675
Our laboratory studies the NF-kB family of transcription factors and the role they play in cell growth and differentiation. Aside from NF-kB’s more recognizable role in regulating immune response, strong evidence suggests that the NF-kB signaling pathway is also involved in tumor progression. However, exactly how NF-kB functions in cellular transformation has not been resolved. To further understand this disease property of NF-kB, my laboratory is using skeletal muscle as a model of cellular growth and differentiation. Skeletal muscle maturation involves growth arrest and fusion of progenitor myoblasts into terminally differentiated myofibers. Our findings have elucidated that NF-kB acts in this system as an inhibitor of differentiation, and we have further identified that this activity can occur through multiple mechanisms. More recently, our group has expanded studies using in vivo models of muscle regeneration, where results support the notion that NF-kB functions in skeletal muscle to limit it’s regenerative potential. We believe this function of NF-kB may be relevant in muscle diseases such as Duchenne muscular dystrophy and cancer cachexia. The long-term goal is to not only to better dissect the function and mechanisms by which NF-kB regulates muscle differentiation and turnover associated with muscle disorders, but to also translate this information into better understanding the role of NF-kB in developing tumors.
Education & Training:
University of California, San Diego, 1986 B.A. in Biochemistry and Cell Biology
California State University, Long Beach, 1988 M.S. in Biochemistry
University of California, Irvine 1996 Ph.D. Biological Sciences
University of North Carolina, Chapel Hill, 2000, Postdoctoral Fellow
For a complete list of publications please visit the National Institutes of Health PubMed web site at: http://www.ncbi.nlm.nih.gov/pubmed?term=Guttridge%20D
- Guttridge, D. C., Mayo, M. W., Madrid, L. V., Wang, C. Y., and Baldwin, A. B. Jr. (2000) NF-kB-Induced Loss of MyoD messenger RNA: Possible Role in Muscle Decay and Cachexia. Science, 289: 2363-2366.
- Ladner, K.J., Caligiuri, M. A., Guttridge, D. C. (2003). TNF Induces the Biphasic Activation of NF-kB in Skeletal Muscle Leading to Cytokine-Induced Protein Loss. J. Biol. Chem. 278: 2294-2303.
- Acharyya S., Ladner K. J., Nelsen L. L., Damrauer J., Reiser P. J., Swoap S., and Guttridge, D. C. (2004) Cancer Cachexia is Regulated by Selective Targeting of Skeletal Muscle Gene Products, J. Clin. Invest., 114: 370-378.
- Hertlein, E., Wang, J., Ladner, K. L., Bakkar, N., Guttridge, D.C. (2005) RelA/p65 Regulation of IkBb., Mol. Cell. Biol., 25: 4956-4968.
- Acharyya S., Butchbach M.E.R., Sahenk, Z., Wang, H., Saji, M., Carathers, M., Ringel, M.D., Skipworth, R.J.E., Fearon, K.C.H., Hollingsworth, M.A., Muscarella, P., Burghes, A.H.M., Rafael-Fortney, J.A., and Guttridge, D. C. (2005) Dystrophin Glycoprotein Complex Dysfunction: A Regulatory Link Between Muscular Dystrophy and Cancer Cachexia, Cancer Cell, 8: 421-432.
- Acharyya, S., Villalta, S. A., Bakkar, N., Bupha-Intr, T., Janssen, P. M., Carathers, M., Li, Z-W., Beg, A., Ghosh, S., Sahenk, Z., Weinstein, M., Gardner, K. L., Rafael-Fortney, J. A., Karin, M., Tidball, J. G., Baldwin, S. A., and Guttridge, D. C. (2007) IKK/NF-kB signaling interplay in macrophages and myofibers promotes muscle degeneration in Duchenne muscular dystrophy, J. Clin. Invest, 117: 889-901.
- Wang, H., Hertlein, E., Bakkar, N., Sun, H., Acharyya, S., Wang, J., Carathers, M., Davuluri, R. and Guttridge, D. C., (2007) NF-kB inhibits skeletal myogenesis through regulation of YY1 and transcriptional silencing of myofibrillar genes. Mol. Cell. Biol., 27: 4374-4387.
- Bakkar, N., Wang, J., Ladner, K., Wang, H., Dahlman, J., Carathers, M., Acharyya, S., Rudnicki, M. A., Hollenbach, A. D., and Guttridge, D. C., (2008) IKK/NF-kB regulates skeletal myogenesis via a signaling switch to inhibit differentiation and promote mitochondrial biogenesis, J. Cell. Biol.,180: 787-802.
- Wang, H., Garzon, R., Sun, H., Ladner, K. L., Singh, R., Cheng, A., Hall, B., Qualman, S. J., Chandler, D., Croce, C., and Guttridge, D.C., (2008) NF-kB-YY1-miR-29 Regulatory Circuitry in Skeletal Myogenesis and Rhabdomyosarcoma, Cancer Cell, 14:369-381.