Director, Darby Children’s Research Institute
Associate Director, Translational Sciences at
Hollings Cancer Center
Education & Training:
University of California, San Diego, 1986, B.S. in Cell Biology and Biochemistry
California State University, Long Beach, 1990, M.S. in Chemistry
University of California, Irvine, 1996, Ph.D. in Molecular Genetics
University of North Carolina, Chapel Hill, 2001, Postdoctoral Fellow
Research Interests:
The Guttridge laboratory is focused on the NF-kB signaling pathway and how this pathway regulates cellular differentiation and tumorigenesis. Using skeletal muscle as a model system of differentiation new insights for muscle related pathologies have led to research in four main areas:
Involuntary weight loss in cancer patients referred to as cachexia that results in muscle wasting
Duchenne muscular dystrophy which is caused by degeneration of skeletal and cardiac muscle
Rhabdomyosarcoma, which is a childhood cancer that often develops in skeletal muscle
Pancreatic cancer, which exhibits one of the highest incidences of cachexia and muscle loss
The laboratory is also interested in developing NF-kB inhibitors or compounds that inhibit downstream effectors of the NF-kB pathway as potential therapies against, cancer cachexia, muscular dystrophy, rhabdomyosarcoma, and pancreatic cancer.
Highlight Publications:
1. 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; PMID: 11009425
2. Acharyya S., ButchbachM.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; PMID: 16286249
3. 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; PMID: 17380205
4. 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; PMID: 18977326
5. 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; PMID: 18299349
6. 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) IKKa and Alternative NF-kB Regulate PGC-1b to Promote Oxidative Muscle Metabolism, J. Cell Biol.196:497-511; PMID: 22351927
7. He, W.,Berardi, E., Cardillo, V.M., Acharyya, S., Aulino, P., Thomas-Ahner, J., Wang, D.J., Bloomstom, M., Muscarella, P., Nau, P., Shah, N., Butchbach, M.E.R., Ladner, K., Adamo, K., Rudnicki, M.A., Keller, C., Coletti, D., Montanaro, F., and https://medicine.musc.edu/departments/pediatrics/about/about-charleston, (2013) NF-kB -mediated Pax7 dysregulation in the muscle microenvironment promotes cancer-related cancer cachexia, J. Clin. Invest., 123:4821–4835; PMID: 24084740
8. Balkhi, M.Y., Iwenofu, O.H., Bakkar, N., Ladner, K.L., Chandler, D, Houghton, P.J., London, C., Kraybill, W., Perrotti, D., Croce, C.M., Keller, C., and Guttridge, D.C., (2013), miR-29 acts as a decoy in sarcomas to protect the tumor suppressor A20 mRNA from degradation by HuR, Science Signaling, 6: ra63; PMID: 23901138
9. Gu, J.,Wang, D. J., Peterson, J. M., Shintaku, J., Liyanarachchi, S., Coppola, V., Frakes, A. E., Kaspar, B., K., Cornelison, D. D., and Guttridge, D. C., (2016), NF-kB – EphrinA5 – dependent communication between NG2+ interstitial cells and myoblasts promotes muscle growth in neonates, Dev. Cell, 36:215-224; PMID: 26777211
10. Shintaku J, Peterson J.M., Talbert E.E., Gu J.M., Ladner K.J., Williams D.R., Mousavi K., Wang R, Sartorelli V, Guttridge D.C., (2016), MyoD regulates skeletal muscle oxidative metabolism cooperatively with alternative NF-kB, Cell Rep. 17:514-526; PMID: 27705798
11. Peterson JM, Wang DJ, Shettigar V, Roof SR, Canan BD, Bakkar N, Shintaku J, Gu JM, Little SC, Ratnam NM, Londhe P, Lu L, Gaw CE, Petrosino JM, Liyanarachchi S, Wang H, Janssen PML, Davis JP, Ziolo MT, Sharma SM, Guttridge DC., (2018), NF-kB inhibition rescues cardiac function by remodeling calcium genes in a Duchenne muscular dystrophy model, Nat Commun., 9: 3431-3445; PMID: 30143619
12. Talbert, E.E., Cuitino, M.C., Ladner, K.J., Rajasekerea, P.V., Siebert, M., Shakya, R., Leone, G.W., Ostrowski, M.C., Paleo, B., Weisleder, N., Reiser, P.J., Webb, A., Timmers, C.D., Eiferman, D.S., Evan, D.C., Dillhof, M.E., Schmidt, C.R., and Guttridge, D.C. (2019), Modeling Human Cancer-induced Cachexia, Cell Rep., 28, 1612-1622; PMID: 3139073