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Dan Noonan Research Interests | Publications | PubMed My laboratory conducts a multi-faceted research program directed at understanding the mechanism(s) by which steroids and other lipophilic hormones and xenobiotics mediate both normal and carcinogenic pathways. Steroid/nuclear receptors, upon interaction with their cognate ligand, bind DNA. Both the rate and pattern of gene expression mediated by DNA bound receptor appears to be dictated by a complex of coregulatory proteins, which bind the receptor and interact with basal transcription complexes. Our studies have recently identified several novel coregulators of steroid/nuclear receptor family members. These coregulatory proteins appear to directly impact the ability of cells to respond to hormonal stimulation at both the gene expression and cell proliferation level. We have further demonstrated that mutation of at least one of these proteins (tuberin) directly impacts the pathologies of both tuberous sclerosis (TSC, for more information see: http://www.tsalliance.org/), an often fatal disease marked by abnormal cellular proliferation and migration, and lymphangioleiomyomatosis (LAM, for more info see: http://lam.uc.edu/), a rare but fatal female-specific lung cancer. Our current studies attempt to resolve the mechanism(s) by which these steroid receptor coregulatory proteins impact gene expression and cellular proliferation. To this end, our research utilizes 'state of the art' molecular, cellular and structural analyses aimed at delineating the intracellular signaling pathways these coregulatory proteins help to define, their role in the pathogenesis of these diseases and potential therapeutic targets for disease intervention.
1. Spencer, M. L., Theodosiou, M. & Noonan, D. J. (2004). NPDC-1, a novel regulator of neuronal proliferation, is degraded by the ubiquitin/proteasome system through a PEST degradation motif. J Biol Chem. 279, 37069-37078. 2. Finlay G.A., B. York, R.H. Karas, B.L. Fanburg, H. Zhang, D.J. Kwiatkowski, and D.J. Noonan. (2004) Estrogen-induced smooth muscle cell growth is regulated by tuberin and associated with altered activation of platelet-derived growth factor receptor-beta and ERK-1/2. J. Biol. Chem. 279, 23114-23122. 3. York, B., Lou, D., Panettieri, R.A., Krymskaya, V.P., Vanaman, T.C. & Noonan, D.J. (2005) Crosstalk between tuberin, calmodulin and estrogen signaling pathways. FASEB J. 19, 1202-1204. 4. Goncharova, E.A., Goncharova, D.A., Lim, P.N., Noonan, D.J. & Krymskaya, V.P. (2005) Modulation of LAM cell migration and invasiveness by tumor suppressor TSC2. Amer. J. of Resp. Cell and Molec. Med. Epub ahead of print] PMID: 16388022 5. Goncharova, E.A., Goncharova, D.A., Spaits, M., Noonan, D.J., Tolovskaya, E., Eszterhas, A. & Krymskaya, V.P. (2006) Abnormal smooth muscle cell growth in lymphangioleiomyomatosis (LAM): role for tumor suppressor TSC2. Amer. J. of Resp. Cell and Molec. Med. Jan 19; [Epub ahead of print] PMID: 16424383 6. York, R.B., Lou, D., & Noonan, D.J. (2006) Tuberin’s nuclear localization can be regulated by phosphorylation at its carboxyl terminus. Mol. Can. Res. (in press). 7. Theodosiou, M. Monaghan, J.R., Spencer, M.L., Voss, S. R. Voss, & Noonan, D.J. (2006) Isolation and characterization of axolotl NPDC-1 and its effects on retinoic acid receptor signaling. Comp. Physiol. Biochem. (submitted). |
