Mailing address:
University of Colorado School of Pharmacy
Mail Stop C238
12850 E. Montview Blvd. V20-2103
Aurora, CO 80045
Office Location:
Pharmacy and Pharmaceutical Sciences Building (V20)
Second Floor
Room 2103
Lab Location:
Pharmacy and Pharmaceutical Sciences Building (V20)
Second Floor
Room 2420E
Contact:
Affiliation:
- Member - University of Colorado Cancer Center
Training and Education:
- BS, Chemistry, University of Missouri-Columbia
- PhD, University of Missouri-Columbia
- Postdoctoral Fellow, Division of Hematology/Oncology, University of Alabama at Birmingham.
Research Interests:
My laboratory studies the signal transduction pathways and molecular mechanisms that regulate apoptotic cell death in response to various extracellular stimuli. Our current research efforts are focused on understanding the dynamic regulation of the glutathione antioxidant defense system during cell death and how alterations in glutathione biosynthetic capacity dictate cellular sensitivity to cell death. Mammalian cells possess a number of antioxidant defense mechanisms to counteract the deleterious effects of oxidative stress.
Glutathione (GSH) is the most abundant non-protein thiol antioxidant within the cell and plays a central role in maintaining cellular redox homeostasis and regulating apoptotic cell death. Glutamate cysteine ligase (GCL) is the rate-limiting enzyme in the synthesis of GSH and is composed of a catalytic (GCLC) and a regulatory (GCLM) subunit. We recently demonstrated that GCLC is a target for caspase-mediated cleavage during apoptotic cell death.
We have also identified additional transcriptional and post-translational control mechanisms that regulate GCLC and GCLM expression during apoptotic cell death. These findings provide the basis for our studies examining the molecular mechanisms and functional significance of changes in cellular GSH biosynthetic capacity in various models of apoptosis.
Teaching:
Graduate Program:
- Fundamentals of Pharmaceutical Sciences
- Principals of Toxicology I and III
- Drug Metabolism and Pharmacogenetics
- Methods in Molecular Toxicology
- Ethical Issues in Toxicology and Pharmaceutical Sciences
Professional Program:
- Science Foundations II
- P3 Seminar
Representative Publications:
- Franklin, C.C., Srikanth, S., and A.S. Kraft (1998) Conditional expression of MAP kinase phosphatase-1, MKP-1, is cytoprotective against UV-induced apoptosis. Proc. Natl. Acad. Sci. USA, 95:3014-3019.
- Siitonen, T., Alaruikka, P., Mantymaa, P., Savolainen, E.-R., Kavanagh, T.J., Krejsa, C.M., Franklin, C.C., Kinnula, V., and P. Koistinen (1999) Protection of acute myeloblastic leukemia cells against apoptotic cell death by high glutathione and gamma-glutamylcysteine synthetase levels during etoposide-induced oxidative stress. Annals of Oncology, 10:1361-1367.
- Franklin, C.C., Krejsa, C.M., Pierce, R.H., White, C.C., Fausto, N., and T.J. Kavanagh (2002) Caspase-3-dependent cleavage of the glutamate-L-cysteine ligase catalytic subunit during apoptotic cell death. Am. J. Pathol., 160:1887-1894.
- Pierce, R.H., Franklin, C.C., Campbell, J.S., Tonge, R.P., Chen, W., Fausto, N., Nelson, S.D., and S.A. Bruschi (2002) Cell culture model for acetaminophen-induced cell death in vivo. Biochem. Pharm., 64:413-424.
- Franklin, C.C., Rosenfeld-Franklin, M.E., White, C.C., Kavanagh, T.J., and N. Fausto (2003) TGFb1-induced suppression of glutathione biosynthesis in hepatocytes: caspase-dependent post-translational and caspase-independent transcriptional regulatory mechanisms. FASEB J., 17:1535-1537.
- Krzywanski, D.M., Dickinson, D.A., Iles, K.E., Wigley, A.F., Franklin, C.C., Liu, R.-M., Kavanagh, T.J., and H.J. Forman (2004) Variable regulation of glutamate cysteine ligase subunit proteins affects glutathione biosynthesis in response to oxidative stress. Arch. Biochem. Biophys., 423(1):116-25.
- Botta, D., Franklin, C.C., White, C.C., Krejsa, C.M., Dabrowski, M.J., Pierce, R.H., Fausto, N., and T.J. Kavanagh (2004) Glutamate-cysteine ligase attenuates TNF-induced mitochondrial injury and apoptosis. Free Radic. Biol. Med., 37(5):632-42.
- Tran, P.O., Parker, S.M., Leroy, E., Franklin, C.C., Kavanaugh, T.J., Zhang, T., Zhou, H., Vliet, P., Oseid, E., Harmon, J.S., and R.P. Robertson (2004) Adenoviral overexpression of the glutamylcysteine ligase catalytic subunit protects pancreatic islets against oxidative stress. J. Biol. Chem., 279(52):53988-53993.
- Stringer, K.A., Tobias, M., O’Neill, H.C., and C.C. Franklin (2007) Cigarette Smoke Extract-Induced Suppression of Caspase-3-like Activity Impairs Human Neutrophil Phagocytosis. Am. J. of Physiol.: Lung Cell. Mol. Physiol. 292(6):L1572-9