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Christopher C. Franklin, Ph.D.

Assistant Professor of Molecular Toxicology, Department of Pharmaceutical Sciences

Mailing address:
4200 E. 9th Ave, C238
Denver, CO 80262

Telephone:
Voice:     303-315-2447
Lab:        303-315-2448
Fax:        303-315-0274
E-Mail:   Christopher.Franklin@uchsc.edu

Affiliation:
Member - University of Colorado Cancer Center

Training and Education:
B.S., Chemistry, University of Missouri-Columbia
Ph.D., 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

Recent Publications

Last updated: 2/27/08