Douglas C. Dean, Ph.D.

Education: Douglas C. Dean, Ph.D

B.S., Chemistry and Biology, Ouachita University, Arkadelphia, Arkansas; 1977
Ph.D., Physical Biochemistry, University of Kansas School of Medicine, Kansas City, KS; 1983
Postdoctoral Fellowship (Bert O’Malley), Department of Cell Biology, Baylor College of Medicine; 1983-1985
Postdoctoral Fellowship (Suzanne Bourgeois), Department of Regulatory Biology, Salk Institute for Biological Studies; 1985-1988 

Current Positions: 

Robert & Gretchen Rounsavall Endowed Professor of Ocular Molecular Oncology,  Departments of Medicine and Ophthalmology, University of Louisville
Member, James Graham Brown Cancer Center 

Contact Information: 

Clinical & Translational Research Building
University of Louisville
505 South Hancock Street
Louisville, KY 40202, USA
Phone 502-852-4882

Email: douglas.dean@louisville.edu

Research Description: 

We are interested in events surrounding formation of tumor initiating cells (TIC) and in regulating T-cell influx into tumors.  Lineage tracing in mouse models is being used to follow steps in transition of progenitor and differentiated cell populations to cancer cells.  We are particularly interested in the role of epithelial-to-mesenchymal transition in driving asymmetric cell division in this process. 

Literature Cited: 

  1. Weintraub SJ, Prater CA, Dean DC.  Retinoblastoma protein switches from E2F site positive to negative element.  Nature 1992 Jul 16;358(6383):259-61.  PMID: 1321348.
  2. Weintraub SJ, Chow KN, Luo RX, Zhang SH, He S, Dean DC.  Mechanism of active transcriptional repression by the retinoblastoma protein.  Nature 1995 Jun 29;375(6534):812-5. PMID: 7596417.
  3. Luo RX, Postigo AA, Dean DC.  Rb interacts with histone deacetylase to repress transcription.  Cell 1998 Feb 20;92(4):463-73.  PMID: 9491888. [ https://www.sciencedirect.com/science/article/pii/S009286740080940X?via%3Dihub ]
  4. Zhang HS, Postigo AA, Dean DC.  Active transcriptional repression by the Rb-E2F complex mediates G1 arrest triggered by p16INK4a, TGFbeta, and contact inhibition.  Cell 1999 Apr 2;97(1):53-61.  PMID: 10199402. [ https://www.sciencedirect.com/science/article/pii/S009286740080714X?via%3Dihub ]
  5. Harbour JW, Luo RX, Dei Santi A, Postigo AA, Dean DC.  Cdk phosphorylation triggers sequential intramolecular interactions that progressively block Rb functions as cells move through G1.  Cell 1999 Sep 17;98(6):859-69. PMID: 10499802. [ https://www.sciencedirect.com/science/article/pii/S0092867400815196?via%3Dihub ]
  6. Zhang HS, Gavin M, Dahiya A, Postigo AA, Ma D, Luo RX, Harbour JW, Dean DC.  Exit from G1 and S phase of the cell cycle is regulated by repressor complexes containing HDAC-Rb-hSWI/SNFand Rb-hSWI/SNF.  Cell 2000 Mar 31;101(1):79-89.  PMID: 10778858. [ https://www.sciencedirect.com/science/article/pii/S009286740080625X?via%3Dihub ]
  7. Harbour JW, Dean DC.  The Rb/E2F pathway: expanding roles and emerging paradigms.  Genes & Development 2000 Oct 1;14(19):2393-409.  PMID: 11018009. [ http://genesdev.cshlp.org/content/14/19/2393.long ]
  8. Dahiya A, Wong S, Gonzalo S, Gavin M, Dean DC.  Linking the Rb and polycomb pathways.  Molecular Cell 2001 Sep;8(3):557-69.  PMID: 11583618. [ https://www.sciencedirect.com/science/article/pii/S109727650100346X?via%3Dihub ]
  9. Harbour JW, Dean DC.  Chromatin remodeling and Rb activity.  Current Opinion in Cell Biology 2000 Dec;12(6):685-9.  Review.  PMID: 11063932.
  10. Harbour JW, Dean DC.  Rb function in cell cycle regulation and apoptosis.  Nature Cell Biology 2002 Apr;2(4):E65-7.  PMID: 10783254.
  11. Liu Y, Clem B, Zuba-Surma EK, El-Naggar S, Telang S, Jenson AB, Ratajczak MZ, Chesney J, Dean DC.  Mouse fibroblasts lacking RB1 function form spheres and undergo reprogramming to a cancer stem cell phenotype.  Cell Stem Cell 2009 Apr 3;4:336-47.  PMID: 19341623.  PMCID: PMC2743858.
  12. Liu Y, Sanches-Tillo E, Lu X, Clem B, Telang S, Jenson AB, Cuatrescasas M, Chesney J, Postigo A, Dean DC.  Rb1 family mutation is sufficient for sarcoma initiation.  Nature Communications 2013;4:2650.  doi: 10.1038/ncomms3650.  PMID: 24150016.
  13. Zhang P, Wang L, Rodriguez-Aguayo C, Yuan Y, Debeb BG, Chen D, Sun Y, You MJ, Liu Y, Dean DC, Woodward WA, Liang H, Yang X, Lopez-Berestein G, Sood AK, Hu Y, Ang KK, Chen J, Ma L.  miR-205 acts as a tumour radiosensitizer by targeting ZEB1 and Ubc13.  Nature Communications 2014 Dec 5;5:5671.  doi: 10.1038/ncomms6671.  PMID: 25476932.  PMCID: PMC4377070.
  14. Zhang P, Wei Y, Wang L, Debeb BG, Yuan Y, Zhang J, Yuan J, Wang M, Chen D, Sun Y, Woodward WA, Liu Y, Dean DC, Liang H, Hu Y, Ang KK, Hung MC, Chen J, Ma L.  ATM-mediated stabilization of ZEB1 promotes DNA damage response and radioresistance through CHK1.  Nature Cell Biology 2014 Sep;16(9):864-75.  doi: 10.1038/ncb3013.  Epub 2014 Aug 3.  PMID: 25086746.  PMCID: PMC4150825.
  15. Liu Y, Lu X, Huang L, Wang W, Jiang G, Dean KC, Clem B, Telang S, Jenson AB, Cuatrecasas M, Chesney J, Darling DS, Postigo A, Dean DC.  Different thresholds of ZEB1 are required for Ras-mediated tumor initiation and metastasis.  Nature Communications 2014;5:5660.  PMID: 25434817.
  16. Schreck C, Istvánffy R, Ziegenhain C, Sippenauer T, Ruf F, Henkel L, Gärtner F, Vieth B, Florian MC, Mende N, Taubenberger A, Prendergast Á, Wagner A, Pagel C, Grziwok S, Götze KS, Guck J, Dean DC, Massberg S, Essers M, Waskow C, Geiger H, Schiemann M, Peschel C, Enard W, Oostendorp RA.  Niche WNT5A regulates the actin cytoskeleton during regeneration of hematopoietic stem cells.  Journal of Experimental Medicine 2017 Jan;214(1):165-81.  doi: 10.1084/jem.20151414.  Epub 2016 Dec 20.  PMID: 27998927.
  17. Cortés M, Sanchez-Moral L, de Barrios O, Fernández-Aceñero MJ, Martínez-Campanario MC, Esteve-Codina A, Darling DS, Győrffy B, Lawrence T, Dean DC, Postigo A.  Tumor-associated macrophages (TAMs) depend on ZEB1 for their cancer-promoting roles.  EMBO Journal 2018 Nov 15;36(22):3336-55.  PMID: 29038174. ).
  18. Liu Y, Siles L, Lu X, Dean KC, Cuatrecasas M, Postigo A, Dean DC. Mitotic polarization of transcription factors during asymmetric division establishes fate of forming cancer cells.Nat Commun. 2018 Jun 21;9(1):2424. doi: 10.1038/s41467-018-04663-1.  PMID:29930325
  19. Wang W, Ashwini Kini A, Wang, K, Liu T, Chen Y, Vukmanic E, Emery D, Liu Y, Lu X, Lei Jin L, Lee SJ, Scott PS, Liu X, Dean K, Lu Q, Fortuny E, James R, Kaplan HJ, Du J, and Dean DC.  2019. Metabolic Deregulation of the Blood-Outer Retinal Barrier in Retinitis Pigmentosa.  Cell Reports 2019 Jul 30;28(5):1323-1334.e4. doi10.1016/j.celrep.2019.06.093. PMID:31365873
  20. Guo Y, Lu X, Chen Y, Rendon B, Mitchell RA, Cuatrecasas M, Cortés M, Postigo A, Liu Y, Dean DC.Zeb1 induces immune checkpoints to form an immunosuppressive envelope around invading cancer cells.  Science Advances. 2021 May 21;7(21):eabd7455. doi: 10.1126/sciadv.abd7455. Print 2021 May.PMID: 34020945