DeFranco Lab

The DeFranco laboratory has spent over 30 years examining glucocorticoid receptor function focusing predominantly on the mechanisms of receptor transactivation, interaction with coactivators, subcellular and subnuclear trafficking, interactions with molecular chaperones and processing. Over the years they have utilized various experimental model systems to provide novel mechanistic insights into receptor action. Some of their studies utilized neuronal cell systems and in particular using cells of hippocampal origin we provided one of the first demonstrations of developmentally regulated receptor degradation that is likely to be influenced by a receptor co-chaperone (e.g. CHIP). In the past few years they have initiated collaborations with Dr. Paula Monaghan-Nichols, a developmental neurobiologist, Dr. Selma Witchel, a pediatric endocrinologist and Dr. Anthony Rudine, a neonatologist, to expand our analysis of glucocorticoid receptor function to an area of clinical relevance.  Clinical and preclinical studies of postnatal and antenatal glucocorticoid administration suggest that detrimental effects of these hormones on neural function in adults and juveniles may be caused by alterations in the proliferation and differentiation of embryonic neural stem cells. The DeFranco laboratory therefore utilizes state-of-the-art genomic approaches, unique transgenic models and primary neural stem/progenitor cell cultures to uncover molecular mechanisms responsible for the detrimental effects of glucocorticoids on the developing brain.
 
The DeFranco laboratory also studies androgen receptor and estrogen receptor function with a particular emphasis on examining coregulators that  impact androgen action in prostate and the regulation of estrogen receptor function by oxidative stress and TGFß signaling. For example, they have identified a novel class of androgen receptor coregulators that are members of the Group III LIM domain family that includes the focal adhesion protein paxillin. Hic-5 is one such group III LIM domain protein highly related to paxillin that they have characterized as an androgen receptor and vitamin D receptor coregulator. Interestingly Hic-5 expression is restricted to the stromal compartment of the prostate gland and represents a novel tissue-specific coregulator that influences stromal/epithelial communication mediated by androgens and vitamin D. Their most recent work has identified a novel paracrine communication network between prostate epithelial and stromal cells that impacts estrogen receptor beta function.
 

Donald B. DeFranco, PhD
Professor & Vice Chair for Medical Education, Associate Dean for Medical Student Research

Donald B. DeFranco, PhD

Liu TT, Grubisha MJ, Frahm KA, Wendell SG, Liu J, Ricke WA, Auchus RJ & DeFranco DB (2016). Opposing effects of cyclooxygenase-2 on estrogen receptor-ß response to 5a-reductase inhibition in prostate epithelial cells. J. Biol. Chem. 291:14747-14760.  PMCID:  PMC4938192

 
Frahm KA, Peffer ME, Zhang JY, Luthra S, Chakka AB, Couger MB, Chandran UR, Monaghan AP & DeFranco DB (2016). The dexamethasone transcriptome in hypothalamic embryonic neural stem cells. Molecular Endocrin. 30, 144-154. PMCID:  PMC4695633
 
Leach DA, Need EF, Toivanen R, Trotta AP, Palenthorpe HM, Tamblyn DJ, Kopsaftis T, England GM, Smith E, Drew PA, Pinnock CB, Lee P, Holst J, Risbridger GP, Chopra S, DeFranco DB, Taylor RA and Buchanan G.  Stromal androgen receptor regulates the composition of the microenvironment to influence prostate cancer outcome.  Oncotarget 6:16135-16150, 2015.

Solomon JD, Heitzer MD, Liu TT, Beumer JH, Parise RA, Normolle DP, Leach DA, Buchanan G and DeFranco DB.  VDR activity is differentially affected by Hic-5 in prostate cancer and stromal cells. Mol Cancer Res 12:1166-1180, 2014.

Peffer ME, Chandran UR, Luthra S, Volonte D, Galbiati F, Garabedian MJ, Monaghan AP and DeFranco DB.  Caveolin-1 regulates genomic action of the glucocorticoid receptor in neural stem cells.  Mol Cell Biol 34:2611-2623, 2014.

Indyk JA, Candido-Vitto C, Wolf IM, Venkataraman S, Munoz R, Saladino RA, Witchel SF and DeFranco DB.  Reduced glucocorticoid receptor protein expression in children with critical illness.  Horm Res Paediatr 79:169-178, 2013.

Samarasinghe RA, Di Maio R, Volonte D, Galbiati F, Lewis M, Romero G and DeFranco DB. Nongenomic glucocorticoid receptor action regulates gap junction intercellular communication and neural progenitor cell proliferation. Proc Natl Acad Sci USA 108:16657-16662, 2011.