W. Douglas Cress
Researcher

W. Douglas Cress

Academic Rank: Associate Member

Overview

The E2F pathway can drive cell death. Understanding the E2F pathway in human cancer may lead to better lung cancer chemotherapy

Discipline

    • Molecular Oncology
    • Thoracic Oncology
    • Melanoma Research Center of Excellence
    • Cancer Biology and Evolution Program
    • Center for Infection Research in Cancer
    • Lung Cancer Center of Excellence

Education & Training

    • Michigan State University, East Lansing, Michigan, PhD - Biochemistry
    • Duke University Medical Center, Durham, North Carolina, Postdoctoral Fellow
Research

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.  

Publications

  • Cress WD, Yu P, Wu J. Expression and alternative splicing of the cyclin-dependent kinase inhibitor-3 gene in human cancer. Int J Biochem Cell B. 2017 May. Pubmedid: 28504190.
  • Cress WD. A stitch in time and CDK9. Cell Cycle. 2017 May;16(9):823-824. Pubmedid: 28301263. Pmcid: PMC5444345.
  • Schabath MB, Cress D, Munoz-Antonia T. Racial and Ethnic Differences in the Epidemiology and Genomics of Lung Cancer. Cancer Control. 2016 Oct;23(4):338-346. Pubmedid: 27842323. Pmcid: PMC5340153.
  • Schabath MB, Welsh EA, Fulp WJ, Chen L, Teer JK, Thompson ZJ, Engel BE, Xie M, Berglund AE, Creelan BC, Antonia SJ, Gray JE, Eschrich SA, Chen DT, Cress WD, Haura EB, Beg AA. Differential association of STK11 and TP53 with KRAS mutation-associated gene expression, proliferation and immune surveillance in lung adenocarcinoma. Oncogene. 2016 Jun;35(24):3209-3216. Pubmedid: 26477306. Pmcid: PMC4837098.
  • Chen L, Engel BE, Welsh EA, Yoder SJ, Brantley SG, Chen DT, Beg AA, Cao C, Kaye FJ, Haura EB, Schabath MB, Cress WD. A Sensitive NanoString-Based Assay to Score STK11 (LKB1) Pathway Disruption in Lung Adenocarcinoma. J Thorac Oncol. 2016 Jun;11(6):838-849. Pubmedid: 26917230. Pmcid: PMC4877210.
  • Chen Z, Li JL, Lin S, Cao C, Gimbrone NT, Yang R, Fu DA, Carper MB, Haura EB, Schabath MB, Lu J, Amelio AL, Cress WD, Kaye FJ, Wu L. cAMP/CREB-regulated LINC00473 marks LKB1-inactivated lung cancer and mediates tumor growth. J Clin Invest. 2016 Jun;126(6):2267-2279. Pubmedid: 27140397. Pmcid: PMC4887185.
  • Jhuraney A, Woods NT, Wright G, Rix L, Kinose F, Kroeger JL, Remily-Wood E, Cress WD, Koomen JM, Brantley SG, Gray JE, Haura EB, Rix U, Monteiro AN. PAXIP1 Potentiates the Combination of WEE1 Inhibitor AZD1775 and Platinum Agents in Lung Cancer. Mol Cancer Ther. 2016 Jul;15(7):1669-1681. Pubmedid: 27196765. Pmcid: PMC4936941.
  • Chen DT, Huang PY, Lin HY, Haura EB, Antonia SJ, Cress WD, Gray JE. Strategies for power calculations in predictive biomarker studies in survival data. Oncotarget. 2016 Dec;7(49):80373-80381. Pubmedid: 27661007. Pmcid: PMC5348326.
  • Chen L, Kurtyka CA, Welsh EA, Rivera JI, Engel BE, Muñoz-Antonia T, Yoder SJ, Eschrich SA, Creelan BC, Chiappori AA, Gray JE, Ramirez JL, Rosell R, Schabath MB, Haura EB, Chen DT, Cress WD. Early2 factor (E2F) deregulation is a prognostic and predictive biomarker in lung adenocarcinoma. Oncotarget. 2016 Dec;7(50):82254-82265. Pubmedid: 27756884. Pmcid: PMC5347689.
  • Challa S, Guo J, Ding X, Xu CX, Li Y, Kim D, Smith MA, Cress WD, Coppola D, Haura EB, Cheng JQ. IKBKE Is a Substrate of EGFR and a Therapeutic Target in Non-Small Cell Lung Cancer with Activating Mutations of EGFR. Cancer Res. 2016 Aug;76(15):4418-4429. Pubmedid: 27287717. Pmcid: PMC4970891.
  • Baldelli E, Bellezza G, Haura EB, Crinó L, Cress WD, Deng J, Ludovini V, Sidoni A, Schabath MB, Puma F, Vannucci J, Siggillino A, Liotta LA, Petricoin EF, Pierobon M. Functional signaling pathway analysis of lung adenocarcinomas identifies novel therapeutic targets for KRAS mutant tumors. Oncotarget. 2015 Oct;6(32):32368-32379. Pubmedid: 26468985. Pmcid: PMC4741699.
  • Baldelli E, Haura EB, Crinò L, Cress WD, Ludovini V, Schabath MB, Liotta LA, Petricoin EF, Pierobon M. Impact of upfront cellular enrichment by laser capture microdissection on protein and phosphoprotein drug target signaling activation measurements in human lung cancer: Implications for personalized medicine. Proteom Clin Appl. 2015 Oct;9(9-10):928-937. Pubmedid: 25676683. Pmcid: PMC4547918.
  • Sosa-García B, Vázquez-Rivera V, González-Flores JN, Engel BE, Cress WD, Santiago-Cardona PG. The Retinoblastoma Tumor Suppressor Transcriptionally Represses Pak1 in Osteoblasts. PLoS One. 2015 Nov;10(11):e0142406. Pubmedid: 26555075. Pmcid: PMC4640669.
  • Cao C, Gao R, Zhang M, Amelio AL, Fallahi M, Chen Z, Gu Y, Hu C, Welsh EA, Engel BE, Haura EB, Cress WD, Wu L, Zajac-Kaye M, Kaye FJ. Role of LKB1-CRTC1 on glycosylated COX-2 and response to COX-2 inhibition in lung cancer. J Natl Cancer Inst. 2015 Jan;107(1):358. Pubmedid: 25465874. Pmcid: PMC4271078.
  • Fan C, Chen L, Huang Q, Shen T, Welsh EA, Teer JK, Cai J, Cress WD, Wu J. Overexpression of major CDKN3 transcripts is associated with poor survival in lung adenocarcinoma. Brit J Cancer. 2015 Dec;113(12):1735-1743. Pubmedid: 26554648. Pmcid: PMC4701993.
  • Kurtyka CA, Chen L, Cress WD. E2F inhibition synergizes with paclitaxel in lung cancer cell lines. PLoS One. 2014 May;9(5):e96357. Pubmedid: 24831239. Pmcid: PMC4022639.
  • Donatelli SS, Zhou JM, Gilvary DL, Eksioglu EA, Chen X, Cress WD, Haura EB, Schabath MB, Coppola D, Wei S, Djeu JY. TGF-β-inducible microRNA-183 silences tumor-associated natural killer cells. Proc Natl Acad Sci U S A. 2014 Mar;111(11):4203-4208. Pubmedid: 24586048. Pmcid: PMC3964044.
  • Chen L, Muñoz-Antonia T, Cress WD. Trim28 contributes to EMT via regulation of E-cadherin and N-cadherin in lung cancer cell lines. PLoS One. 2014 Jul;9(7):e101040. Pubmedid: 24983967. Pmcid: PMC4077753.
  • Cress WD, Chiappori A, Santiago P, Muñoz-Antonia T. Lung cancer mutations and use of targeted agents in Hispanics. Rev Recent Clin Trials. 2014 Dec;9(4):225-232. Pubmedid: 25626064. Pmcid: PMC4441412.
  • 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.
  • 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. 2012 Mar;6(10):e24923. Pubmedid: 22046235. Pmcid: PMC3203112.
  • Cress WD. E2F1: A new role in the DNA damage response. Cell Cycle. 2011 Jun;10(11):1718. Pubmedid: 21543892. Pmcid: PMC3685611.
  • 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.
  • 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 Nov;5(11):e13954. Pubmedid: 21085651. Pmcid: PMC2978706.
  • 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.
  • 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.
  • 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 Dec;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.
  • 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. Pmcid: PMC2268526.
  • 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.
  • 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. Pmcid: PMC2134790.
  • 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):1088-1089. Pubmedid: 16030308.
  • 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.
  • 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.
  • 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.
  • Ma Y, Freeman SN, Cress WD. E2F4 deficiency promotes drug-induced apoptosis. Cancer Biol Ther. 2004 Dec;3(12):1262-1269. Pubmedid: 15611646.
  • 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.
  • Croxton R, Ma Y, Cress W. Differences in DNA binding properties between E2F1 and E2F4 specify repression of the Mcl-1 promoter. Oncogene. 2002 Feb;21(10):1563-1570. Pubmedid: 11896585.
  • Croxton R, Ma Y, Song L, Haura E, Cress W. Direct repression of the Mcl-1 promoter by E2F1. Oncogene. 2002 Feb;21(9):1359-1369. Pubmedid: 11857079.
  • 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.
  • 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.
  • 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 Bioph Res Co. 2000 Oct;276(3):930-939. Pubmedid: 11027571.
  • 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.
  • 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.
  • Cress, Jr. W, Seto E. Histone deacetylases, transcriptional control, and cancer. J Cell Physiol. 2000;184(1):1-16. Pubmedid: 10825229.
  • 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 Mar;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.
  • 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, 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.
  • 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.