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Dianne R. Soprano, PhDDianne R. Soprano, PhD

 

Interim Chairperson, Department of Biochemistry
Professor, Biochemistry
Professor, Fels Institute for Cancer Research and Molecular Biology
Associate Dean, Graduate and MD/PhD Program

Telephone:  215-707-3266

Fax:  215-707-7536

Email: dsoprano@temple.edu

 

Dean's Staff

Department of Biochemistry

Fels Institute for Cancer Research and Molecular Biology

Graduate and MD/PhD Program

 

Educational Background:

 

PhD,  Rutgers University, 1975-1980

 

Postdoctoral Fellow, Columbia University College of Physicians and Surgeons, 1980-1982

 

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Research Interests:

 

Research in Dr. Soprano's laboratory focuses on the mechanism of action of retinoic acid (RA) at the molecular level. RA exerts its action by the transcriptional regulation of specific genes via a family of nuclear receptors called retinoic acid receptors, RARs, and retinoid X receptors, RXRs. Three distinct but highly homologous RAR isotypes have been described termed RARα, RARβ and RARγ. In addition, several isoforms of each RAR isotype, which vary in both the length and amino acid sequence of the N-terminal A domain, have been identified. Specifically, we are interested in the structure, function and regulation of RARs particularly during development and in tumors.

 

First, the mRNA and protein levels of pre-B cell leukemia transcription factors (PBXs) are elevated by RA in mouse limb buds and in P19 embryonal carcinoma cells. Abrogation of the RA-dependent increase in PBX expression in P19 cells results in a failure of these cells to differentiate to either endodermal or neuronal cells demonstrating the importance of PBX in the cascade of RA-dependent changes in gene expression during differentiation. Microarray analysis has resulted in the identification of a number of genes whose expression is regulated by RA treatment in wild type cells but not in cells that fail to increase PBX expression. Currently we are addressing the role of these genes during RA-dependent differentiation of P19 cells to endodermal and neuronal cells.

 

These studies are aimed at the elucidation of the sequence of events involved in RA-mediating differentiation of pluripotent embryonal carcinoma cells to endodermal and neuronal cells. Second, little is known about the functional importance of the unique A/B domains associated with each of the isoforms of the three RAR isotypes. Yeast 2-hybrid screening has resulted in the identification of several unique cDNAs that encode proteins including Acinus and HACE1 that interact with the amino terminal A/B domain of RARs. Acinus has been suggested to be a splicing factor and HACE1 has E3 ubiquitin ligase activity. The role of these proteins in the regulation of RA-dependent gene expression is being explored with the goal of further understanding the functional importance of the A/B domains of RARs. Third, RA can inhibit the growth of many tumor cells including the CAOV3 ovarian tumor cell line. In addition, several synthetic retinoids induce apoptosis in ovarian tumor cells. Studies are currently underway examining the steps in the apoptotic pathway induced by several synthetic retinoids and the mechanism of regulation of the protein levels of the tumor suppressor gene, Rb2, during RA-induced growth inhibition of these cells. Elucidation of the mechanism of action underlying RA-dependent inhibition of tumor cell growth may lead to the development of unique retinoid treatments for cancer chemotherapy and chemoprevention. 

 

 

Model of RAR Genomic Action

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LABORATORY PERSONNEL:

 

Dorret Garner   -   Research Assistant

Z.P. Zhang -  Research Assistant

Thais Acquafreda – Postdoctoral Fellow

Brandy Pickens -  Graduate Student

Bryan Teets -  Graduate  Student

Fang Wang – Graduate Student

Erin Payne – Graduate Student

Evelyn Sirisani – Graduate Student

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PUBMED PUBLICATIONS :


Recent Medically Related Publications, Obtained from PubMed (Click on PubMed ID to view abstract)

25205379. Wang F, Soprano KJ, Soprano DR, Role of Acinus in Regulating Retinoic Acid-responsive Gene Pre-mRNA Splicing. J Cell Physiol :()2014 Sep 9

25079509. Wang F, Wendling KS, Soprano KJ, Soprano DR, Role of the SAP Motif and the C-terminal RS- and RD/E-rich Region in the Sub-Nuclear Localization of Acinus Isoforms. J Cell Biochem :()2014 Jul 30

23018522. Pickens BS, Teets BW, Soprano KJ, Soprano DR, Role of COUP-TFI during retinoic acid-induced differentiation of P19 cells to endodermal cells. J Cell Physiol 228:4(791-800)2013 Apr

21678401. Teets BW, Soprano KJ, Soprano DR, Role of SF-1 and DAX-1 during differentiation of P19 cells by retinoic acid. J Cell Physiol 227:4(1501-11)2012 Apr

20857408. Purev E, Soprano DR, Soprano KJ, PP2A interaction with Rb2/p130 mediates translocation of Rb2/p130 into the nucleus in all-trans retinoic acid-treated ovarian carcinoma cells. J Cell Physiol 226:4(1027-34)2011 Apr

19502054. Sun W, Carroll PJ, Soprano DR, Canney DJ, Identification of a chromone-based retinoid containing a polyolefinic side chain via facile synthetic routes. Bioorg Med Chem Lett 19:15(4339-42)2009 Aug 1

19350571. Zhao J, Zhang Z, Vucetic Z, Soprano KJ, Soprano DR, HACE1: A novel repressor of RAR transcriptional activity. J Cell Biochem 107:3(482-93)2009 Jun 1

18615582. Radu M, Soprano DR, Soprano KJ, S10 phosphorylation of p27 mediates atRA induced growth arrest in ovarian carcinoma cell lines. J Cell Physiol 217:2(558-68)2008 Nov

18446820. Fields AL, Soprano DR, Soprano KJ, Characterization of alterations of Rb2/p130 tumor suppressor in all-trans-retinoic acid resistant SK-OV3 ovarian carcinoma cells. J Cell Physiol 217:1(77-85)2008 Oct

18250153. Vucetic Z, Zhang Z, Zhao J, Wang F, Soprano KJ, Soprano DR, Acinus-S' represses retinoic acid receptor (RAR)-regulated gene expression through interaction with the B domains of RARs. Mol Cell Biol 28:8(2549-58)2008 Apr

17909034. Ravikumar S, Perez-Liz G, Del Vale L, Soprano DR, Soprano KJ, Insulin receptor substrate-1 is an important mediator of ovarian cancer cell growth suppression by all-trans retinoic acid. Cancer Res 67:19(9266-75)2007 Oct 1

17902161. Fields AL, Soprano DR, Soprano KJ, Retinoids in biological control and cancer. J Cell Biochem 102:4(886-98)2007 Nov 1

17474084. Jiang T, Soprano DR, Soprano KJ, GADD45A is a mediator of CD437 induced apoptosis in ovarian carcinoma cells. J Cell Physiol 212:3(771-9)2007 Sep

17368312. Soprano DR, Teets BW, Soprano KJ, Role of retinoic acid in the differentiation of embryonal carcinoma and embryonic stem cells. Vitam Horm 75:(69-95)2007

17073551. Buletic Z, Soprano KJ, Soprano DR, Retinoid targets for the treatment of cancer. Crit Rev Eukaryot Gene Expr 16:3(193-210)2006

16936753. Soprano KJ, Purev E, Vuocolo S, Soprano DR, Rb2/p130 and protein phosphatase 2A: key mediators of ovarian carcinoma cell growth suppression by all-trans retinoic acid. Oncogene 25:38(5315-25)2006 Aug 28

16206244. Purev E, Giordano A, Soprano DR, Soprano KJ, Interaction of PP2A catalytic subunit with Rb2/p130 is required for all-trans retinoic acid suppression of ovarian carcinoma cell growth. J Cell Physiol 206:2(495-502)2006 Feb

16052510. Ramírez CJ, Haberbusch JM, Soprano DR, Soprano KJ, Retinoic acid induced repression of AP-1 activity is mediated by protein phosphatase 2A in ovarian carcinoma cells. J Cell Biochem 96:1(170-82)2005 Sep 1

15354417. Purev E, Soprano DR, Soprano KJ, Effect of all-trans retinoic acid on telomerase activity in ovarian cancer cells. J Exp Clin Cancer Res 23:2(309-16)2004 Jun

15189119. Soprano DR, Qin P, Soprano KJ, Retinoic acid receptors and cancers. Annu Rev Nutr 24:(201-21)2004

15131049. D'Andrilli G, Masciullo V, Bagella L, Tonini T, Minimo C, Zannoni GF, Giuntoli RL 2nd, Carlson JA Jr, Soprano DR, Soprano KJ, Scambia G, Giordano A, Frequent loss of pRb2/p130 in human ovarian carcinoma. Clin Cancer Res 10:9(3098-103)2004 May 1

15095411. Qin P, Haberbusch JM, Soprano KJ, Soprano DR, Retinoic acid regulates the expression of PBX1, PBX2, and PBX3 in P19 cells both transcriptionally and post-translationally. J Cell Biochem 92:1(147-63)2004 May 1

15095280. Holmes WF, Soprano DR, Soprano KJ, Synthetic retinoids as inducers of apoptosis in ovarian carcinoma cell lines. J Cell Physiol 199:3(317-29)2004 Jun

15040006. Vuocolo S, Soprano DR, Soprano KJ, p27/Kip1 mediates retinoic acid-induced suppression of ovarian carcinoma cell growth. J Cell Physiol 199:2(237-43)2004 May

14742427. Qin P, Haberbusch JM, Zhang Z, Soprano KJ, Soprano DR, Pre-B cell leukemia transcription factor (PBX) proteins are important mediators for retinoic acid-dependent endodermal and neuronal differentiation of mouse embryonal carcinoma P19 cells. J Biol Chem 279:16(16263-71)2004 Apr 16

14508518. Holmes WF, Soprano DR, Soprano KJ, Early events in the induction of apoptosis in ovarian carcinoma cells by CD437: activation of the p38 MAP kinase signal pathway. Oncogene 22:41(6377-86)2003 Sep 25

12915404. Vuocolo S, Purev E, Zhang D, Bartek J, Hansen K, Soprano DR, Soprano KJ, Protein phosphatase 2A associates with Rb2/p130 and mediates retinoic acid-induced growth suppression of ovarian carcinoma cells. J Biol Chem 278:43(41881-9)2003 Oct 24

12704790. Holmes WF, Soprano DR, Soprano KJ, Comparison of the mechanism of induction of apoptosis in ovarian carcinoma cells by the conformationally restricted synthetic retinoids CD437 and 4-HPR. J Cell Biochem 89:2(262-78)2003 May 15

12514309. Soprano DR, Soprano KJ, Pharmacological doses of some synthetic retinoids can modulate both the aryl hydrocarbon receptor and retinoid receptor pathways. J Nutr 133:1(277S-281S)2003 Jan

12504905. Zhang ZP, Hutcheson JM, Poynton HC, Gabriel JL, Soprano KJ, Soprano DR, Arginine of retinoic acid receptor beta which coordinates with the carboxyl group of retinoic acid functions independent of the amino acid residues responsible for retinoic acid receptor subtype ligand specificity. Arch Biochem Biophys 409:2(375-84)2003 Jan 15

12468629. Soprano KJ, Soprano DR, Retinoic acid receptors and cancer. J Nutr 132:12(3809S-3813S)2002 Dec

12397630. Qin P, Cimildoro R, Kochhar DM, Soprano KJ, Soprano DR, PBX, MEIS, and IGF-I are potential mediators of retinoic acid-induced proximodistal limb reduction defects. Teratology 66:5(224-34)2002 Nov

12237293. Holmes WF, Soprano DR, Soprano KJ, Elucidation of molecular events mediating induction of apoptosis by synthetic retinoids using a CD437-resistant ovarian carcinoma cell line. J Biol Chem 277:47(45408-19)2002 Nov 22

11857450. Le Q, Soprano DR, Soprano KJ, Profiling of retinoid mediated gene expression in synchronized human SCC cells using Atlas human cDNA expression arrays. J Cell Physiol 190:3(345-55)2002 Mar

11809858. Gambone CJ, Hutcheson JM, Gabriel JL, Beard RL, Chandraratna RA, Soprano KJ, Soprano DR, Unique property of some synthetic retinoids: activation of the aryl hydrocarbon receptor pathway. Mol Pharmacol 61:2(334-42)2002 Feb

11753676. Zhang D, Vuocolo S, Masciullo V, Sava T, Giordano A, Soprano DR, Soprano KJ, Cell cycle genes as targets of retinoid induced ovarian tumor cell growth suppression. Oncogene 20:55(7935-44)2001 Nov 29

11606393. Kumar A, Soprano DR, Parekh HK, Cross-resistance to the synthetic retinoid CD437 in a paclitaxel-resistant human ovarian carcinoma cell line is independent of the overexpression of retinoic acid receptor-gamma. Cancer Res 61:20(7552-5)2001 Oct 15

11446831. Soprano DR, Gambone CJ, Sheikh SN, Gabriel JL, Chandraratna RA, Soprano KJ, Kochhar DM, The synthetic retinoid AGN 193109 but not retinoic acid elevates CYP1A1 levels in mouse embryos and Hepa-1c1c7 cells. Toxicol Appl Pharmacol 174:2(153-9)2001 Jul 15

10942515. Zhang D, Holmes WF, Wu S, Soprano DR, Soprano KJ, Retinoids and ovarian cancer. J Cell Physiol 185:1(1-20)2000 Oct

10933889. Zhang ZP, Shukri M, Gambone CJ, Gabriel JL, Soprano KJ, Soprano DR, Role of Ser(289) in RARgamma and its homologous amino acid residue of RARalpha and RARbeta in the binding of retinoic acid. Arch Biochem Biophys 380:2(339-46)2000 Aug 15

10771516. Soprano DR, Scanlon E, Shukri M, Zhang ZP, Soprano KJ, Murine RARbeta4 displays reduced transactivation activity, lower affinity for retinoic acid, and no anti-AP1 activity. J Cell Biochem 77:4(604-14)2000 Apr

10723137. Le Q, Dawson MI, Soprano DR, Soprano KJ, Modulation of retinoic acid receptor function alters the growth inhibitory response of oral SCC cells to retinoids. Oncogene 19:11(1457-65)2000 Mar 9

9879990. Wu S, Zhang D, Zhang ZP, Soprano DR, Soprano KJ, Critical role of both retinoid nuclear receptors and retinoid-X-receptors in mediating growth inhibition of ovarian cancer cells by all-trans retinoic acid. Oncogene 17:22(2839-49)1998 Dec 3

9852056. Zhang ZP, Gambone CJ, Gabriel JL, Wolfgang CL, Soprano KJ, Soprano DR, Arg278, but not Lys229 or Lys236, plays an important role in the binding of retinoic acid by retinoic acid receptor gamma. J Biol Chem 273:51(34016-21)1998 Dec 18

9708807. Katsetos CD, Stadnicka I, Boyd JC, Ehya H, Zheng S, Soprano CM, Cooper HS, Patchefsky AS, Soprano DR, Soprano KJ, Cellular distribution of retinoic acid receptor-alpha protein in serous adenocarcinomas of ovarian, tubal, and peritoneal origin: comparison with estrogen receptor status. Am J Pathol 153:2(469-80)1998 Aug

9518263. Wu S, Zhang D, Donigan A, Dawson MI, Soprano DR, Soprano KJ, Effects of conformationally restricted synthetic retinoids on ovarian tumor cell growth. J Cell Biochem 68:3(378-88)1998 Mar 1

9417874. Wu S, Zhang ZP, Zhang D, Soprano DR, Soprano KJ, Reduction of both RAR and RXR levels is required to maximally alter sensitivity of CA-OV3 ovarian tumor cells to growth suppression by all-trans-retinoic acid. Exp Cell Res 237:1(118-26)1997 Nov 25

9168803. Wu S, Donigan A, Platsoucas CD, Jung W, Soprano DR, Soprano KJ, All-trans-retinoic acid blocks cell cycle progression of human ovarian adenocarcinoma cells at late G1. Exp Cell Res 232:2(277-86)1997 May 1

9111026. Scafonas A, Wolfgang CL, Gabriel JL, Soprano KJ, Soprano DR, Differential role of homologous positively charged amino acid residues for ligand binding in retinoic acid receptor alpha compared with retinoic acid receptor beta. J Biol Chem 272:17(11244-9)1997 Apr 25

8995359. Wolfgang CL, Zhang Z, Gabriel JL, Pieringer RA, Soprano KJ, Soprano DR, Identification of sulfhydryl-modified cysteine residues in the ligand binding pocket of retinoic acid receptor beta. J Biol Chem 272:2(746-53)1997 Jan 10

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