Donald B. DeFranco, Ph.D.

Professor of Pharmacology,
University of Pittsburgh School of Medicine
Vice Chair for Education,
Department of Pharmacology



Don DeFranco received his BA in biology from Temple University and his PhD in Molecular Biophysics and Biochemistry from Yale University. After serving as a postdoctoral fellow in the Department of Biochemistry at the University of California, San Francisco, he joined the faculty of the Biological Sciences Department at the University of Pittsburgh in 1985. He joined the Pharmacology Department at the University of Pittsburgh School of Medicine in 2000 and in addition to his appointment in the Pittsburgh Institute of Neurodegenerative Diseases, he holds a secondary appointment in the Department of Neuroscience and is an affiliate member of the Magee Women’s Research Institute and the University of Pittsburgh Cancer Institute. He is Editor-in-Chief of Molecular Endocrinology, and has extensive grant review experience including his most recent appointment on the National Institute of General Medical Sciences (NIGMS) Biomedical Research and Research Training Subcommittee.

A number of projects in Dr. DeFranco’s laboratory are focused on examining the molecular basis of neuronal cell death. One group uses various models of oxidative toxicity (e.g. neuronal cell lines, primary neurons) to study the impact of intracellular signaling molecules (e.g. mitogen activated protein kinases or MAPK family members) on neuronal cell survival. Recent work from the DeFranco laboratory established that some kinases previously considered to play a neuroprotective role (i.e. extracellular signal-regulated protein kinase or ERK) could contribute to cell death in response to oxidative stress. The mechanism involved in the different action of ERK and other signaling molecules is the subject of various ongoing projects that utilize biochemical, molecular and cell biological approaches in cell culture and intact animals. Recent results suggest that ERK activation in oxidatively stressed neurons may be driven by zinc-dependent inhibition of select protein phosphatases. Finally, Dr. DeFranco’s laboratory is also interested in the action of glucocorticoid hormones in the brain. For this project they have focused on molecular analysis of the glucocorticoid receptor protein in hippocampal neurons. Recent studies suggest that specific E3 ubiquitin ligases may regulate glucocorticoid receptor function in developing neurons through an impact on receptor processing and downregulation.

Links:

CNUP

Pharmacology and Chemical Biology


Recent Publications:

  • Jiang H, Nucifora F, Ross CA and DeFranco DB,  (2003). Cell death triggered by polyglutamine-expanded huntinigtin in a neuronal cell line is associated with degradation of CREB-binding protein, Human Mol Genet 12:1-12, 2003.
  • Elbi C, Romero G, Walker D, Sullivan W, Toft D, Hager GL, and DeFranco DB, Molecular chaperones function as nuclear mobility factors for steroid receptors, Proc Natl Acad Sci USA 101:2876-2881, 2004.
  • Levinthal DJ and DeFranco DB, Reversible oxidation of ERK-directed protein phosphatases drives oxidative toxicity in neurons, J Biol Chem 280:5875-5883, 2005.
  • Wang X and DeFranco DB, Alternative effects of the ubiquitin-proteasome pathway on glucocorticoid receptor downregulation and transactivation are mediated by the CHIP E3 ligase, Mol Endocrinol 19:1474-1482, 2005.
  • Heitzer MD and DeFranco DB, Hic-5/ARA55 a LIM domain-containing nuclear receptor coactivator expressed in prostate stromal cells, Cancer Res, 66:7326-7333, 2006.
  • Zhang Y, Aizenman E, DeFranco DB and Rosenberg PA, Intracellular zinc release, 12-lipoxygenase activation and MAPK dependent neuronal and oligodendroglial death. Molecular Medicine 13: 350-355, 2007.
  • Ho Y, Logue ES, Callaway CW, DeFranco DB. (2007) Different mechanisms regulating ERK activation in distinct brain regions following global ischemia and reperfusion. Neuroscience 145, 248-255.
  • Heitzer M, DeFranco DB. (2007) Hic-5/ARA55 a prostate stroma-specific AR coactivator. Steroids 72, 218-220.
  • Deklebab B, Witchel SF, DeFranco DB.  (2007) TNF-alpha and glucocorticoid receptor interaction in L6 muscle cells; a cooperative downregulation of myosin heavy chain. Steroids 72, 705-712.
  • Zhang Y, Aizenman E, DeFranco DB, Rosenberg PA.  (2007) Intracellular zinc release, 12-lipoxygenase activation and MAPK dependent neuronal and oligodendroglial death. Molecular Medicine 13, 350-355.
  • Heitzer MD, Wolf IM, Sanchez ER, Witchel SF, DeFranco DB. (2007) Glucocorticoid receptor physiology. Rev Endocr Metab Disort 8, 321-330.
  • Ho Y*, Samarasinghe R*, Knoch ME, Lewis M, Aizenman E, DeFranco DB.  (2008) Selective inhibition of MAPK phosphatases by zinc accounts for ERK1/2-dependent oxidative neuronal cell death.  Molecular Pharmacology 74, 1141-1151. (*co-first authors)
  • Gong H, Jarzynka MJ, Cole TJ, Wada T, Lee J-H, Zhai Y, Song W-C, DeFranco DB, Cheng S, Xie W. (2008) Glucocorticoids antagonize estrogens by glucocorticoid receptor-mediated activation of estrogen sulfotransferase. Cancer Res 68, 7386-7393.
  • Wolf IM, Heitzer MD, Grubisha M, DeFranco DB. (2008) Coactivators and nuclear receptor transactivation. J Cell Biochem. 104, 1580-1586.
  • Nguyen MM, DIncer Z, Wade JR, Alur M, Michalak, M, DeFranco DB,  Wang Z (2009) Cytoplasmic localization of the androgen receptor is independent of calreticulin. Mol. Cell. Endocrinol 10, 65-72.
  • Devinney MJ, Malaiyandi LM, Vergun O, DeFranco DB, Hastings TG, Dineley KE (2009) A comparison of Zn2+- and Ca2+-triggered depolarization of liver mitochondria reveals no evidence of Zn2+-induced permeability transition. Cell Calcium 45, 447-55.
  • Caltagarone J, Hamilton RL, Murdoch G, DeFranco DB, Jing Z, Bowser R. (2010) Analysis of paxillin and hic-5 expression and distribution in the hippocampus of control and Alzheimer’s disease subjects. J Neuropath Exp Neurol, 69, 356-371.
  • Sen A, O'Malley K, Wang Z, Raj GV, DeFranco DB, Hammes S (2010). Paxillin regulates androgen- and epidermal growth factor- induced MAPK signaling and cell proliferation in prostate cancer cells. J Biol Chem 285, 28787-28795.
  • Stankowski J, ZeigerxSL, Cohen EL, DeFranco DB, Cai J, McLaughlin, BA (2011). C-Terminus of HSC70 Interacting Protein Increases Following Stroke and Impairs Survival Against Acute Oxidative Stress. Antioxid Redox Signal. 14,1787-1801.
  • Samarasinghe RA, Di Maio R, Volonte D, Galbiati, F, Lewis M, Romero G, DeFranco DB (2011). Non-genomic glucocorticoid receptor action regulates gap junction intercellular communication and neural progenitor cell proliferation. Proc. Natl. Acad. Sci. USA, in press.