Ohio State - Nationwide Children's Hospital - Research For Muscle Biology and Disease
 

 

Denis C. Guttridge, Ph.D.Denis Guttridge
Professor

The Ohio State University Medical Center
460 W. 12th Avenue
Biomedical Research Tower, 520
Columbus, OH 43210

Phone: (614) 688-4507
Fax: (614) 688-8675
Email: denis.guttridge@osumc.edu

Education & Training:
University of California, San Diego, 1986 B.A. in Biochemistry and Cell Biology
California State University, Long Beach, 1988 M.A. in Biochemistry
University of California, Irvine, 1996 Ph.D. in Biological Sciences
University of North Carolina, Chapel Hill, 2000 Postdoctoral Fellow

Research Interest:
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. To this point, our findings have elucidated that NF-kB acts in immature skeletal muscle cells as an inhibitor of differentiation, and we further identified that this activity occurs through multiple mechanisms. Our group has also 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 conditions including cachexia and rhabdomyosarcoma. The long-term goal is to not only better dissect the function and mechanisms by which NF-kB regulates muscle differentiation associated with muscle disorders, but to also determine whether NF-kB can be targeted therapeutically for the treatment of these diseases.

Selected Publications:

  • 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.
  • 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.
  • 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.
  • Wang, J., Naduparambil, K. J., Ladner, K. J., Beg, A. A., Perko, J. D., Tanner, S. M., Liyanarachchi, S., Fishel, R., and Guttridge, D. C., (2009) RelA/p65 functions to maintain cellular senescence by regulating genomic stability and DNA repair. EMBO Rep. 10: 1272-1278..
  • Acharyya, S., Sharma, S. M. Cheng, A.S., Ladner, K.J., He, W., Kline, W., Wang, H., Ostrowski, M., Huang, T. H., Guttridge, D.C. (2010) TNF inhibits Notch-1 in skeletal muscle cells by Ezh2 and DNA methylation mediated repression: Implications in Duchenne muscular dystrophy, PLoS One, 5(8):e12479.
  • Bakkar, N., Ladner, K., Canan, B. D., Liyanarachchi, S., Bal, N.C., Pant, M., Periasamy, M., Li, Q., Janssen, P.M.L, and Guttridge, D. C., (2012), IKKα and Alternative NF-κB Regulate PGC-1 beta to Promote Oxidative Muscle Metabolism, J. Cell Biol. 196:497-511.
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