W. Douglas Cress, PhD

Depending on the biological context manipulation of the activity of individual members of the E2F family may promote proliferation, may induce growth arrest or may drive programmed cell death.  Our laboratory is focused on understanding the structure, function and regulation of the E2F family expecting that this information will provide a greater understanding of cancer biology and will inform improved cancer therapeutic approaches. 

One area of focus in our lab is to understand a variety of negative feedback loops that retrain E2F1’s death-inducing activity and thus limit chemotherapeutic efficacy of many drugs.  A second area of focus is the identification, development and characterization of novel small molecules that target various steps of the E2F pathway.  And finally, we seek to understand the mechanism that regulate the expression and biological activity of E2F4 a pro-survival member of the E2F family who’s depletion can significantly increase the efficacy of number of stand chemotherapeutic drugs.  

• Chen L, Chen DT, Kurtyka C, Rawal B, Fulp WJ, Haura EB, Cress WD. Tripartite motif containing 28 (Trim28) can regulate cell proliferation by bridging HDAC1/E2F interactions. J Biol Chem. 2012 Nov;287(48):40106-40118. Pubmedid: 23060449. Pmcid: PMC3504725.
• Chen DT, Hsu YL, Fulp WJ, Coppola D, Haura EB, Yeatman TJ, Cress WD. Prognostic and predictive value of a malignancy-risk gene signature in early-stage non-small cell lung cancer. J Natl Cancer Inst. 2011 Dec;103(24):1859-1870. Pubmedid: 22157961. Pmcid: PMC3243673.
• Haviland R, Eschrich S, Bloom G, Ma Y, Minton S, Jove R, Cress WD. Necdin, a Negative Growth Regulator, Is a Novel STAT3 Target Gene Down-Regulated in Human Cancer. PLoS One. 2011 Oct;6(10):e24923. Pubmedid: 22046235.
• Cress WD. E2F1: A new role in the DNA damage response. Cell Cycle. 2011 Jun;10(11):1718. Pubmedid: 21543892.
• Freeman SN, Cress WD. RhoBTB2 (DBC2) comes of age as a multifunctional tumor suppressor. Cancer Biol Ther. 2010 Dec;10(11):1123-1125. Pubmedid: 20980811.
• Ma Y, Chen L, Wright GM, Pillai SR, Chellappan SP, Cress WD. CDKN1C negatively regulates RNA polymerase II C-terminal domain phosphorylation in an E2F1-dependent manner. J Biol Chem. 2010 Mar;285(13):9813-9822. Pubmedid: 20106982. Pmcid: PMC2843230.
• Sosa-García B, Gunduz V, Vázquez-Rivera V, Cress WD, Wright G, Bian H, Hinds PW, Santiago-Cardona PG. A role for the retinoblastoma protein as a regulator of mouse osteoblast cell adhesion: implications for osteogenesis and osteosarcoma formation. PLoS One. 2010;5(11):e13954. Pubmedid: 21085651. Pmcid: PMC2978706.
• Brazelle W, Kreahling JM, Gemmer J, Ma Y, Cress WD, Haura E, Altiok S. Histone deacetylase inhibitors downregulate checkpoint kinase 1 expression to induce cell death in non-small cell lung cancer cells. PLoS One. 2010;5(12):e14335. Pubmedid: 21179472. Pmcid: PMC3001870.
• Corsino P, Horenstein N, Ostrov D, Rowe T, Law M, Barrett A, Aslanidi G, Cress WD, Law B. A novel class of cyclin-dependent kinase inhibitors identified by molecular docking act through a unique mechanism. J Biol Chem. 2009 Oct;284(43):29945-29955. Pubmedid: 19710018. Pmcid: PMC2785623.
• He L, Yang H, Ma Y, Pledger WJ, Cress WD, Cheng JQ. Identification of Aurora-A as a direct target of E2F3 during G2/M cell cycle progression. J Biol Chem. 2008 Nov;283(45):31012-31020. Pubmedid: 18776222. Pmcid: PMC2576560.
• Ma Y, Kurtyka CA, Boyapalle S, Sung SS, Lawrence H, Guida W, Cress WD. A small-molecule E2F inhibitor blocks growth in a melanoma culture model. Cancer Res. 2008 Aug;68(15):6292-6299. Pubmedid: 18676853. Pmcid: PMC3615411.
• Niu G, Briggs J, Deng J, Ma Y, Lee H, Kortylewski M, Kujawski M, Kay H, Cress WD, Jove R, Yu H. Signal transducer and activator of transcription 3 is required for hypoxia-inducible factor-1alpha RNA expression in both tumor cells and tumor-associated myeloid cells. Mol Cancer Res. 2008 Jul;6(7):1099-1105. Pubmedid: 18644974. Pmcid: PMC2775817.
• Freeman SN, Ma Y, Cress WD. Rhobtb2 (DBC2) is a mitotic E2F1 target gene with a novel role in apoptosis. J Biol Chem. 2008 Jan;283(4):2353-2362. Pubmedid: 18039672.
• Wang C, Rauscher FJ 3rd, Cress W, Chen J. Regulation of E2F1 function by the nuclear co-repressor KAP-1. J Biol Chem. 2007 Oct;282(41):29902-9. Pubmedid: 17704056.
• Ma Y, Cress W. Transcriptional upregulation of p57 (Kip2) by the cyclin-dependent kinase inhibitor BMS-387032 is E2F dependent and serves as a negative feedback loop limiting cytotoxicity. Oncogene. 2007 May;26(24):3532-3540. Pubmedid: 17173074.
• Wang C, Chen L, Hou X, Li Z, Kabra N, Ma Y, Nemoto S, Finkel T, Gu W, Cress WD, Chen J. Interactions between E2F1 and SirT1 regulate apoptotic response to DNA damage. Nat Cell Biol. 2006 Sep;8(9):1025-1031. Pubmedid: 16892051.
• Rodriguez JM, Glozak MA, Ma Y, Cress WD. Bok, Bcl-2 related ovarian killer, is cell cycle regulated and sensitizes to stress-induced apoptosis. J Biol Chem. 2006 Aug;281(32):22729-22735. Pubmedid: 16772296.
• Niu G, Wright KL, Ma Y, Wright GM, Huang M, Irby R, Briggs J, Karras J, Cress WD, Pardoll D, Jove R, Chen J, Yu H. Role of Stat3 in regulating p53 expression and function. Mol Cell Biol. 2005 Sep;25(17):7432-7440. Pubmedid: 16107692.
• Freeman S, Bepler G, Haura E, Sutphen R, Cress W. Re: Prognostic significance of a short sequence insertion in the MCL-1 promoter in chronic lymphocytic leukemia. J Natl Cancer Inst. 2005 Jul;97(14):1088-9. Pubmedid: 16030308.
• Wang C, Hou X, Mohapatra S, Ma Y, Cress WD, Pledger WJ, Chen J. Activation of p27Kip1 Expression by E2F1. A negative feedback mechanism. J Biol Chem. 2005 Apr;280(13):12339-12343. Pubmedid: 15713665.
• Bepler G, Zheng Z, Gautam A, Sharma S, Cantor A, Cress W, Kim Y, Rosell R, McBride C, Robinson L, Sommers E, Haura E. Ribonucleotide reductase M1 gene promoter activity, polymorphisms, population frequencies, and clinical relevance. Lung Cancer. 2005 Feb;47(2):183-192. Pubmedid: 15639717.
• Ma Y, Freeman SN, Cress WD. E2F4 deficiency promotes drug-induced apoptosis. Cancer Biol Ther. 2004 Dec;3(12):1262-1269. Pubmedid: 15611646.
• Haura EB, Cress WD, Chellappan S, Zheng Z, Bepler G. Antiapoptotic signaling pathways in non-small-cell lung cancer: biology and therapeutic strategies. Clin Lung Cancer. 2004 Sep;6(2):113-122. Pubmedid: 15476597.
• Hauser P, Ma L, Agrawal D, Haura E, Cress WD, Pledger WJ. Efficient down-regulation of cyclin A-associated activity and expression in suspended primary keratinocytes requires p21(Cip1). Mol Cancer Res. 2004 Feb;2(2):96-104. Pubmedid: 14985466.
• Savell J, Ma Y, Morrow KS, Jove R, Olashaw N, Moseley PL, Cress WD, Wharton W. AG490 inhibits G1-S traverse in BALB/c-3T3 cells following either mitogenic stimulation or exogenous expression of E2F-1. Mol Cancer Ther. 2004 Feb;3(2):205-213. Pubmedid: 14985461.
• Wang J, Gamsby J, Highfill S, Mora L, Bloom G, Yeatman T, Pan T, Ramne A, Chodosh L, Cress W, Chen J, Kerr W. Deregulated expression of LRBA facilitates cancer cell growth. Oncogene. 2004;23(23):4089-4097. Pubmedid: 15064745.
• Ma Y, Yuan J, Huang M, Jove R, Cress WD. Regulation of the cyclin D3 promoter by E2F1. J Biol Chem. 2003 May;278(19):16770-16776. Pubmedid: 12611887.
• Ma Y, Cress WD, Haura EB. Flavopiridol-induced apoptosis is mediated through up-regulation of E2F1 and repression of Mcl-1. Mol Cancer Ther. 2003 Jan;2(1):73-81. Pubmedid: 12533675.
• Wen YD, Cress WD, Roy AL, Seto E. Histone deacetylase 3 binds to and regulates the multifunctional transcription factor TFII-I. J Biol Chem. 2003;278(3):1841-1847. Pubmedid: 12393887.
• Ma Y, Croxton R, Moorer R, Cress W. Identification of novel E2F1-regulated genes by microarray. Arch Biochem Biophys. 2002;399(2):212-224. Pubmedid: 11888208.
• He Y, Cress W. E2F-3B is a physiological target of cyclin A. J Biol Chem. 2002;277(26):23493-23499. Pubmedid: 11980909.
• Croxton R, Ma Y, Song L, Haura E, Cress W. Direct repression of the Mcl-1 promoter by E2F1. Oncogene. 2002;21(9):1359-1369. Pubmedid: 11857079.
• Croxton R, Ma Y, Cress W. Differences in DNA binding properties between E2F1 and E2F4 specify repressionof the Mcl-1 promoter. Oncogene. 2002;21(10):1563-1570. Pubmedid: 11896585.
• Cuenca A, Cress W, Good R, Marikar Y, Engelman R. Calorie restriction influences cell cycle protein expression and DNA synthesis during liver regeneration. Exp Biol Med (Maywood). 2001;226(11):1061-1067. Pubmedid: 11743143.
• Wharton W, Savell J, Cress WD, Seto E, Pledger WJ. Inhibition of mitogenesis in Balb/c-3T3 cells by Trichostatin A. Multiple alterations in the induction and activation of cyclin-cyclin-dependent kinase complexes. J Biol Chem. 2000 Oct;275(43):33981-33987. Pubmedid: 10945992.
• Zhang X, Wharton W, Donovan M, Coppola D, Croxton R, Cress WD, Pledger WJ. Density-dependent growth inhibition of fibroblasts ectopically expressing p27(kip1). Mol Biol Cell. 2000 Jun;11(6):2117-2130. Pubmedid: 10848633.
• Cress, Jr. W, Seto E. Histone deacetylases, transcriptional control, and cancer. J Cell Physiol. 2000;184(1):1-16. Pubmedid: 10825229.
• He Y, Armanious M, Thomas MJ, Cress, Jr. W. Identification of E2F-3B, an alternative form of E2F-3 lacking a conserved N-terminal region. Oncogene. 2000;19(30):3422-3433. Pubmedid: 10918599.
• Hu X, Cress, Jr. W, Zhong Q, Zuckerman K. Transforming growth factor beta inhibits the phosphorylation of pRB at multiple serine/threonine sites and differentially regulates the formation of pRB family-E2F complexes in human myeloid leukemia cells. Biochem Biophys Res Commun. 2000;276(3):930-939. Pubmedid: 11027571.
• Dong F, Cress WD, Agrawal D, Pledger WJ. The role of cyclin D3-dependent kinase in the phosphorylation of pRb2/p130 in mouse BALB/c 3T3 fibroblasts. J Biol Chem. 1998 Mar;273(11):6190-6195. Pubmedid: 9497341.
• Flores A, Kassatly R, Cress, Jr. W. E2F-3 accumulation is regulated by polypeptide stability. Oncogene. 1998;16(10):1289-1298. Pubmedid: 9546430.
• Tao Y, Kassatly R, Cress, Jr. W, Horowitz J. Subunit composition determines E2F DNA-binding site specificity. Mol Cell Biol. 1997;17(12):6994-7007. Pubmedid: 9372931.
• Cress, Jr. W, Nevins J. A role for bent DNA structure in E2F-mediated transcription activation. Mol Cell Biol. 1996;16:2119-2127. Pubmedid: 8628278.
• Cress, Jr. W, Nevins J. Interacting domains of E2F1, DP1 and the adenovirus E4 protein. J Virol. 1994;68:4212-4219.
• Cress, Jr. W, Johnson J, Nevins J. Genetic analysis of the E2F1 gene distinguishes regulation by Rb, p107 and adenovirus E4. Mol Cell Biol. 1993;13:6314-6325.
• Johnson D, Schwarz J, Cress, Jr. W, Nevins J. Expression of transcription factor E2F1 can induce quiescent cells to enter S phase. Nature. 1993;365:349-352.
• Cress, Jr. W, Nevins J. Use of the E2F transcription factor by DNA tumor virus regulatory proteins. In: P. J. Farnham, ed. Current topics in microbiology and immunology. 208 ed. Germany. Springer Verlag Berlin Heidelberg; 1996.