David G. Johnson, Ph.D.
Department of Epigenetics and Molecular Carcinogenesis, Division of Basic Sciences
Present Title & Affiliation
Primary Appointment
Professor, Department of Epigenetics and Molecular Carcinogenesis, Division of Science Park, The University of Texas MD Anderson Cancer Center, Houston, TX
Dual/Joint/Adjunct Appointment
Adjunct Professor, Department of College of Pharmacy, Division of Pharmacology and Toxicology, University of Texas at Austin, Austin, TX
Research Interests
Cancer genetics, DNA damage response, apoptosis, cell cycle My current research is focused on two transcription factors that respond to DNA damage and play important roles in regulating tumor development. The first project focuses on E2F1, a regulator of genes important for cell cycle progression and apoptosis. We have discovered that E2F1 localizes to sites of both DNA double-strand breaks and UV-induced DNA damage and that this involves the phosphorylation of E2F1 by the ATM or ATR kinases. Moreover, our studies demonstrate that E2F1 recruits chromatin-modifying enzymes to sites of damage to facilitate access to the DNA repair machinery. These findings indicate that E2F1 stimulates DNA repair through a non-transcriptional mechanism that functions in the context of chromatin. The physiological relevance of E2F1 in the DNA damage response is now being explored using a novel knock-in mouse model we developed that blocks E2F1 phosphorylation by ATM/ATR.
The other project involves the study of a single nucleotide polymorphism (SNP) in the human p53 gene that results in either arginine (R) or proline (P) at position 72 of the p53 protein. This SNP affects the apoptotic activity of p53 but the mechanistic basis and physiologic relevance of this phenotypic difference remain unclear. We have developed mouse models that mimic this human SNP and have demonstrated that the humanized p53 variants are functional and display the expected difference in apoptotic capacity in mouse tissues. These models are being used to explore the roles of this human SNP in modulating cancer susceptibility and the response to DNA damaging agents, including chemotherapeutic drugs.
Education & Training
Degree-Granting Education
| 1991 | University of Texas Southwestern Medical Center, Dallas, TX, USA, PHD, Microbiology |
| 1985 | University of Texas, Austin, TX, USA, BA, Microbiology |
Postgraduate Training
| 1991-1994 | Research Fellowship, Molecular Genetics, Howard Hughes Medical Institute, Duke University Medical Center, Durham, NC |
Experience & Service
Academic Appointments
Associate Professor, Department of Epigenetics and Molecular Carcinogenesis, Division of Basic Science Research, University of Texas M.D. Anderson Cancer Center, Smithville, TX, 2000 - 2006
Assistant Professor, Department of Epigenetics and Molecular Carcinogenesis, Division of Basic Science Research, University of Texas M.D. Anderson Cancer Center, Smithville, TX, 1994 - 2000
Honors & Awards
| 2021 | Oldham Faculty Award, Graduate School of Biomedical Sciences |
| 2019 | President's Recognition of Faculty Excellence Award in Education & Mentorship Advancement, The University of Texas MD Anderson Cancer Center |
| 2017 | Commendation, Graduate School of Biomedical Sciences |
| 2012 | Commendation, Graduate School of Biomedical Sciences |
| 2011 | Faculty Educator of the Month: May, The University of Texas MD Anderson Cancer Center |
| 2007 | Commendation, Graduate School of Biomedical Sciences |
| 2000 | Faculty Scholar Award, UT MD Anderson Cancer Center |
| 1996 | Junior Faculty Scholar, American Cancer Society |
| 1991 | Postdoctoral Fellowship, American Cancer Society |
Selected Publications
Peer-Reviewed Articles
- Manickavinayaham S, Vélez-Cruz R, Biswas AK, Bedford E, Klein BJ, Kutateladze TG, Liu B, Bedford MT, Johnson DG. E2F1 acetylation directs p300/CBP-mediated histone acetylation at DNA double-strand breaks to facilitate repair. Nat Commun 10(1):4951, 2019. e-Pub 2019. PMID: 31666529.
- Ortiz GJ, Li Y, Post SM, Pant V, Xiong S, Larsson CA, El-Naggar AK, Johnson DG, Lozano G. Contrasting effects of an Mdm2 functional polymorphism on tumor phenotypes. Oncogene 37(3):332-340, 2018. e-Pub 2017. PMID: 28925402.
- Domínguez ER, Orona J, Lin K, Pérez CJ, Benavides F, Kusewitt DF, Johnson DG. The p53 R72P polymorphism does not affect the physiological response to ionizing radiation in a mouse model. Cell Cycle 16(12):1153-1163, 2017. e-Pub 2017. PMID: 28594296.
- Vélez-Cruz R, Manickavinayaham S, Biswas AK, Clary RW, Premkumar T, Cole F, Johnson DG. RB localizes to DNA double-strand breaks and promotes DNA end resection and homologous recombination through the recruitment of BRG1. Genes Dev 30(22):2500-2512, 2016. PMID: 27940962.
- Hossain MB, Shifat R, Johnson DG, Bedford MT, Gabrusiewicz KR, Cortes-Santiago N, Luo X, Lu Z, Ezhilarasan R, Sulman EP, Jiang H, Li SS, Lang FF, Tyler J, Hung MC, Fueyo J, Gomez-Manzano C. TIE2-mediated tyrosine phosphorylation of H4 regulates DNA damage response by recruiting ABL1. Sci Adv 2(4):e1501290, 2016. e-Pub 2016. PMID: 27757426.
- Sarkar J, Dominguez E, Li G, Kusewitt DF, Johnson DG. Modeling gene-environment interactions in oral cavity and esophageal cancers demonstrates a role for the p53 R72P polymorphism in modulating susceptibility. Mol Carcinog 53(8):648-58, 2014. e-Pub 2013. PMID: 23475592.
- Biswas AK, Mitchell DL, Johnson DG. E2F1 Responds to Ultraviolet Radiation by Directly Stimulating DNA Repair and Suppressing Carcinogenesis. Cancer Res 74(12):3369-77, 2014. e-Pub 2014. PMID: 24741006.
- Perez CJ, Rundhaug JE, Johnson DG, Oberyszyn TM, Tober KL, Kusewitt DF. Slug Expression in Mouse Skin and Skin Tumors Is Not Regulated by p53. J Invest Dermatol 134(2):566-8, 2014. e-Pub 2013. PMID: 24008423.
- Guan X, Liu Z, Wang L, Johnson DG, Wei Q. Identification of prohibition and prohibiton as novel factors binding to the p53 induced gene 3 (PIG3) promoter (TGYCC)15 motif. Biochem Biophys Res Commun 443(4):1239-1244, 2014. e-Pub 2014. PMID: 24388982.
- Lu M, Liu Z, Yu H, Wang LE, Li G, Sturgis EM, Johnson DG, Wei Q. Combined effects of E2F1 and E2F2 polymorphisms on risk and early onset of squamous cell carcinoma of the head and neck. Mol Carcinog 51 Suppl 1:E132-41, 2012. e-Pub 2012. PMID: 22344756.
- Yu H, Huang YJ, Liu Z, Wang LE, Li G, Sturgis EM, Johnson DG, Wei Q. Effects of MDM2 promoter polymorphisms and p53 codon 72 polymorphism on risk and age at onset of squamous cell carcinoma of the head and neck. Mol Carcinog 50(9):697-706, 2011. e-Pub 2011. PMID: 21656578.
- Chen J, Zhu F, Weaks RL, Biswas AK, Guo R, Li Y, Johnson DG. E2F1 promotes the recruitment of DNA repair factors to sites of DNA double-strand breaks. Cell Cycle 10(8):1287-94, 2011. PMID: 21512314.
- Guo R, Chen J, Mitchell DL, Johnson DG. GCN5 and E2F1 stimulate nucleotide excision repair by promoting H3K9 acetylation at sites of damage. Nucleic Acids Res 39(4):1390-7, 2011. e-Pub 2010. PMID: 20972224.
- Valdez CD, Davis JN, Odeh HM, Layfield TL, Cousineau CS, Berton TR, Johnson DG, Wojno KJ, Day ML. Repression of Androgen Receptor Transcription through the E2F1/DNMT1 Axis. PLoS One 6(9):e25187, 2011. e-Pub 2011. PMID: 21966451.
- Jiang H, Martin V, Gomez-Manzano C, Johnson DG, Alonso M, White E, Xu J, McDonnell TJ, Shinojima N, Fueyo J. The RB-E2F1 Pathway Regulates Autophagy. Cancer Res 70(20):7882-93, 2010. e-Pub 2010. PMID: 20807803.
- Jiang Y, Wang X, Bao S, Guo R, Johnson DG, Shen X, Li L. INO80 chromatin remodeling complex promotes the removal of UV lesions by the nucleotide excision repair pathway. Proc Natl Acad Sci U S A 107(40):17274-17279, 2010. e-Pub 2010. PMID: 20855601.
- Post SM, Quintás-Cardama A, Pant V, Iwakuma T, Hamir A, Jackson JG, Maccio DR, Bond GL, Johnson DG, Levine AJ, Lozano G. A high-frequency regulatory polymorphism in the p53 pathway accelerates tumor development. Cancer Cell 18(3):220-230, 2010. PMID: 20832750.
- Zhu F, Dollé ME, Berton TR, Kuiper RV, Capps C, Espejo A, McArthur MJ, Bedford MT, van Steeg H, de Vries A, Johnson DG. Mouse Models for the p53 R72P Polymorphism Mimic Human Phenotypes. Cancer Res 70(14):5851-5859, 2010. e-Pub 2010. PMID: 20587514.
- Guo R, Chen J, Zhu F, Biswas AK, Berton TR, Mitchell DL, Johnson DG. E2F1 localizes to sites of UV-induced DNA damage to enhance nucleotide excision repair. J Biol Chem 285(25):19308-19315, 2010. e-Pub 2010. PMID: 20413589.
- Pusapati RV, Weaks RL, Rounbehler RJ, McArthur MJ, Johnson DG. E2F2 suppresses Myc-induced proliferation and tumorigenesis. Mol Carcinog 49(2):152-6, 2010. PMID: 19798698.
- Rojas P, Benavides F, Blando J, Perez C, Cardenas K, Richie E, Knudsen ES, Johnson DG, Senderowicz AM, Rodriguez-Puebla ML, Conti CJ. Enhanced skin carcinogenesis and lack of thymus hyperplasia in transgenic mice expressing human cyclin D1b (CCND1b). Mol Carcinog 48(6):508-16, 2009. PMID: 18942117.
- Paulson QX, Pusapati RV, Hong S, Weaks RL, Conti CJ, Johnson DG. Transgenic expression of E2F3a causes DNA damage leading to ATM-dependent apoptosis. Oncogene 27(36):4954-61, 2008. e-Pub 2008. PMID: 18469863.
- Hong S, Paulson QX, Johnson DG. E2F1 and E2F3 activate ATM through distinct mechanisms to promote E1A-induced apoptosis. Cell Cycle 7(3):391-400, 2008. e-Pub 2007. PMID: 18235226.
- Akli S, Van Pelt CS, Bui T, Multani AS, Chang S, Johnson D, Tucker S, Keyomarsi K. Overexpression of the low molecular weight cyclin E in transgenic mice induces metastatic mammary carcinomas through the disruption of the ARF-p53 pathway. Cancer Res 67(15):7212-22, 2007. PMID: 17671189.
- Olson MV, Johnson DG, Jiang H, Xu J, Alonso MM, Aldape KD, Fuller GN, Bekele BN, Yung WK, Gomez-Manzano C, Fueyo J. Transgenic E2F1 expression in the mouse brain induces a human-like bimodal pattern of tumors. Cancer Res 67(9):4005-9, 2007. PMID: 17483310.
- Russell JL, Weaks RL, Berton TR, Johnson DG. E2F1 suppresses skin carcinogenesis via the ARF-p53 pathway. Oncogene 25(6):867-76, 2006. PMID: 16205640.
- Paulson QX, McArthur MJ, Johnson DG. E2F3a stimulates proliferation, p53-independent apoptosis and carcinogenesis in a transgenic mouse model. Cell Cycle 5(2):184-90, 2006. e-Pub 2006. PMID: 16340309.
- Pusapati RV, Rounbehler RJ, Hong S, Powers JT, Yan M, Kiguchi K, McArthur MJ, Wong PK, Johnson DG. ATM promotes apoptosis and suppresses tumorigenesis in response to Myc. Proc Natl Acad Sci U S A 103(5):1446-51, 2006. PMID: 16432227.
- Alonso MM, Fueyo J, Shay JW, Aldape KD, Jiang H, Lee OH, Johnson DG, Xu J, Kondo Y, Kanzawa T, Kyo S, Bekele BN, Zhou X, Nigro J, McDonald JM, Yung WK, Gomez-Manzano C. Expression of transcription factor E2F1 and telomerase in glioblastomas: mechanistic linkage and prognostic significance. J Natl Cancer Inst 97(21):1589-600, 2005. PMID: 16264179.
- Berton TR, Mitchell DL, Guo R, Johnson DG. Regulation of epidermal apoptosis and DNA repair by E2F1 in response to ultraviolet B radiation. Oncogene 24(15):2449-60, 2005. PMID: 15735727.
- Rundhaug JE, Hawkins KA, Pavone A, Gaddis S, Kil H, Klein RD, Berton TR, McCauley E, Johnson DG, Lubet RA, Fischer SM, Aldaz CM. SAGE profiling of UV-induced mouse skin squamous cell carcinomas, comparison with acute UV irradiation effects. Mol Carcinog 42(1):40-52, 2005. PMID: 15547921.
- Miliani de Marval PL, Macias E, Rounbehler R, Sicinski P, Kiyokawa H, Johnson DG, Conti CJ, Rodriguez-Puebla ML. Lack of cyclin-dependent kinase 4 inhibits c-myc tumorigenic activities in epithelial tissues. Mol Cell Biol 24(17):7538-47, 2004. PMID: 15314163.
- Powers JT, Hong S, Mayhew CN, Rogers PM, Knudsen ES, Johnson DG. E2F1 uses the ATM signaling pathway to induce p53 and Chk2 phosphorylation and apoptosis. Mol Cancer Res 2(4):203-14, 2004. PMID: 15140942.
- Berton TR, Matsumoto T, Page A, Conti CJ, Deng CX, Jorcano JL, Johnson DG. Tumor formation in mice with conditional inactivation of Brca1 in epithelial tissues. Oncogene 22(35):5415-26, 2003. PMID: 12934101.
- Wikonkal NM, Remenyik E, Knezevic D, Zhang W, Liu M, Zhao H, Berton TR, Johnson DG, Brash DE. Inactivating E2f1 reverts apoptosis resistance and cancer sensitivity in Trp53-deficient mice. Nat Cell Biol 5(7):655-60, 2003. PMID: 12833065.
- Rounbehler RJ, Rogers PM, Conti CJ, Johnson DG. Inactivation of E2f1 enhances tumorigenesis in a Myc transgenic model. Cancer Res 62(11):3276-81, 2002. PMID: 12036945.
- Russell JL, Powers JT, Rounbehler RJ, Rogers PM, Conti CJ, Johnson DG. ARF differentially modulates apoptosis induced by E2F1 and Myc. Mol Cell Biol 22(5):1360-8, 2002. PMID: 11839803.
- Rounbehler RJ, Schneider-Broussard R, Conti CJ, Johnson DG. Myc lacks E2F1's ability to suppress skin carcinogenesis. Oncogene 20(38):5341-9, 2001. PMID: 11536046.
- Wang D, Russell J, Xu H, Johnson DG. Deregulated expression of DP1 induces epidermal proliferation and enhances skin carcinogenesis. Mol Carcinog 31(2):90-100, 2001. PMID: 11429786.
- Wang A, Johnson DG, MacLeod MC. Molecular cloning and characterization of a novel mouse epidermal differentiation gene and its promoter. Genomics 73(3):284-90, 2001. PMID: 11350120.
- Zhang SY, Liu SC, Johnson DG, Klein-Szanto AJ. E2F-1 gene transfer enhances invasiveness of human head and neck carcinoma cell lines. Cancer Res 60(21):5972-6, 2000. PMID: 11085515.
- Wang D, Russell JL, Johnson DG. E2F4 and E2F1 have similar proliferative properties but different apoptotic and oncogenic properties in vivo. Mol Cell Biol 20(10):3417-24, 2000. PMID: 10779331.
- Wang A, Schneider-Broussard R, Kumar AP, MacLeod MC, Johnson DG. Regulation of BRCA1 expression by the Rb-E2F pathway. J Biol Chem 275(6):4532-6, 2000. PMID: 10660629.
- Wang A, Pierce A, Judson-Kremer K, Gaddis S, Aldaz CM, Johnson DG, MacLeod MC. Rapid analysis of gene expression (RAGE) facilitates universal expression profiling. Nucleic Acids Res 27(23):4609-18, 1999. PMID: 10556317.
- Pierce AM, Schneider-Broussard R, Gimenez-Conti IB, Russell JL, Conti CJ, Johnson DG. E2F1 has both oncogenic and tumor-suppressive properties in a transgenic model. Mol Cell Biol 19(9):6408-14, 1999. PMID: 10454586.
- Rodriguez-Puebla ML, LaCava M, Gimenez-Conti IB, Johnson DG, Conti CJ. Deregulated expression of cell-cycle proteins during premalignant progression in SENCAR mouse skin. Oncogene 17(17):2251-8, 1998. PMID: 9811455.
- Pierce AM, Gimenez-Conti IB, Schneider-Broussard R, Martinez LA, Conti CJ, Johnson DG. Increased E2F1 activity induces skin tumors in mice heterozygous and nullizygous for p53. Proc Natl Acad Sci U S A 95(15):8858-63, 1998. PMID: 9671769.
- Pierce AM, Schneider-Broussard R, Philhower JL, Johnson DG. Differential activities of E2F family members: unique functions in regulating transcription. Mol Carcinog 22(3):190-8, 1998. PMID: 9688145.
- Pierce AM, Fisher SM, Conti CJ, Johnson DG. Deregulated expression of E2F1 induces hyperplasia and cooperates with ras in skin tumor development. Oncogene 16(10):1267-76, 1998. PMID: 9546428.
- Rodriguez-Puebla ML, Robles AI, Johnson DG, LaCava M, Conti CJ. Synchronized proliferation induced by 12-O-tetradecanoylphorbol-13-acetate treatment of mouse skin: an in vivo model for cell cycle regulation. Cell Growth Differ 9(1):31-9, 1998. PMID: 9438386.
- Johnson DG, Coleman A, Powell KL, MacLeod MC. High-affinity binding of the cell cycle-regulated transcription factors E2F1 and E2F4 to benzo[a]pyrene diol epoxide-DNA adducts. Mol Carcinog 20(2):216-23, 1997. PMID: 9364211.
- Butler AP, Johnson DG, Kumar AP, Narayan S, Wilson SH, MacLeod MC. Disruption of transcription in vitro and gene expression in vivo by DNA adducts derived from a benzo[a]pyrene diol epoxide located in heterologous sequences. Carcinogenesis 18(2):239-44, 1997. PMID: 9054613.
- Johnson DG. Regulation of E2F-1 gene expression by p130 (Rb2) and D-type cyclin kinase activity. Oncogene 11(9):1685-92, 1995. PMID: 7478595.
- Johnson DG, Cress WD, Jakoi L, Nevins JR. Oncogenic capacity of the E2F1 gene. Proc Natl Acad Sci U S A 91(26):12823-7, 1994. PMID: 7809128.
- Johnson DG, Ohtani K, Nevins JR. Autoregulatory control of E2F1 expression in response to positive and negative regulators of cell cycle progression. Genes Dev 8(13):1514-25, 1994. PMID: 7958836.
- Cress WD, Johnson DG, Nevins JR. A genetic analysis of the E2F1 gene distinguishes regulation by Rb, p107, and adenovirus E4. Mol Cell Biol 13(10):6314-25, 1993. PMID: 8413230.
- Johnson DG, Schwarz JK, Cress WD, Nevins JR. Expression of transcription factor E2F1 induces quiescent cells to enter S phase. Nature 365(6444):349-52, 1993. PMID: 8377827.
- Cooper C, Johnson D, Roman C, Avitahl N, Tucker P, Calame K. The C/EBP family of transcriptional activators is functionally important for Ig VH promoter activity in vivo and in vitro. J Immunol 149(10):3225-31, 1992. PMID: 1431100.
- Johnson DG, Carayannopoulos L, Capra JD, Tucker PW, Hanke JH. The ubiquitous octamer-binding protein(s) is sufficient for transcription of immunoglobulin genes. Mol Cell Biol 10(3):982-90, 1990. PMID: 2304473.
Invited Articles
- Manickavinayaham S, Dennehey BK, Johnson DG. Direct regulation of DNA repair by E2F and RB in mammals and plants: Core function or convergent evolution?. Cancers (Basel) 13(5):934, 2021. e-Pub 2021. PMID: 33668093.
- Manickavinayaham S, Velez-Cruz R, Biswas AK, Chen J, Guo R, Johnson DG. The E2F1 transcription factor and RB tumor suppressor moonlight as DNA repair factors. Cell Cycle 19(18):2260-2269, 2020. e-Pub 2020. PMID: 32787501.
- Vélez-Cruz R, Johnson DG. The Retinoblastoma (RB) Tumor Suppressor: Pushing Back against Genome Instability on Multiple Fronts. Int J Mol Sci 18(8), 2017. e-Pub 2017. PMID: 28812991.
- Johnson DG, Dent SY. Chromatin: Receiver and Quarterback for Cellular Signals. Cell 152(4):685-9, 2013. e-Pub 2013. PMID: 23375745.
- Vélez-Cruz R, Johnson DG. E2F1 and p53 Transcription Factors as Accessory Factors for Nucleotide Excision Repair. Int J Mol Sci 10(13):13554-68, 2012. e-Pub 2012. PMID: 23202967.
- Biswas AK, Johnson DG. Transcriptional and Nontranscriptional Functions of E2F1 in Response to DNA Damage. Cancer Res 72(1):13-7, 2012. e-Pub 2011. PMID: 22180494.
- Johnson DG, Degregori J. Putting the oncogenic and tumor suppressive activities of E2F into context. Curr Mol Med 6(7):731-8, 2006. PMID: 17100599.
- DeGregori J, Johnson DG. Distinct and overlapping roles for E2F family members in transcription, proliferation, and apoptosis. Curr Mol Med 6(7):739-48, 2006. PMID: 17100600.
- Hong S, Pusapati RV, Powers JT, Johnson DG. Oncogenes and the DNA damage response: Myc and E2F1 engage the ATM signaling pathway to activate p53 and induce apoptosis. Cell Cycle 5(8):801-3, 2006. e-Pub 2006. PMID: 16582589.
- Johnson DG, Rogers PM. E2F murine models of human carcinogenesis. Recent Res Dev Mol Cell Biol 3(2):455-70, 2002.
- Johnson DG. The paradox of E2F1: oncogene and tumor suppressor gene. Mol Carcinog 27(3):151-7, 2000. PMID: 10708476.
- Johnson DG, Walker CL. Cyclins and cell cycle checkpoints. Annu Rev Pharmacol Toxicol 39:295-312, 1999. PMID: 10331086.
- Johnson DG, Schneider-Broussard R. Role of E2F in cell cycle control and cancer. Front Biosci 3:d447-8, 1998. PMID: 9556498.
- Johnson DG, Richie ER, Conti CJ. The cell cycle and cancer. Cancer Bull 47:480-5, 1995.
Book Chapters
- Alson M, Fueyo J, Johnson DG, Gomez-Manzano C. The oncogenic role of E2F1 in brain tumors. In: Control of Cellular Physiology by Transcription Factors E2F. Research Signpost, 2008.