 ' | David G. Johnson, Ph.D. |
Primary Appointment
Dual/Joint/Adjunct Appointment
Cancer genetics, DNA damage response, apoptosis, cell cycle
My current research is focused on 2 main areas. The first involves the role of the E2F1 transcription factor in the response to DNA damage. In particular, we are interested in exploring a direct, nontranscriptional role for E2F1 in the repair of several types of DNA damage, including double-strand breaks and UV-induced photoproducts. We find that phosphorylation of E2F1 by ATM or ATR at serine 31 leads to the accumulation of E2F1 at sites of DNA damage. Our studies indicate that E2F1 stimulates efficient repair by recruiting the GCN5 histone acetyltransferase and other chromatin-modifying enzymes to sites of damage to facilitate access to the DNA repair machinery. We are now developing a knockin mouse model to further explore the physiological relevance of E2F1 in the DNA damage response.
The other area of research is examining how cells sense the deregulated expression of oncogenes and the role of the oncogenic stress response in suppressing tumorigenesis. We have found that overexpression of the oncogenic transcription factors Myc and E2F3 causes DNA breaks both in vitro and in vivo, and we are trying to understand how this damage arises. We have also found that the ATM kinase is involved in sensing oncogene-induced DNA damage and is important for activating p53 and inducing apoptosis in response to oncogenic stress. We are now examining the role of other components of the ATM network in sensing oncogene-induced DNA damage and suppressing the development of cancer.
In addition to these 2 main areas of research, we are also developing and characterizing humanized mouse models for the p53 R72P polymorphism. These models will be used to explore the role of this human single-nucleotide polymorphism (SNP) in modulating cancer susceptibility and the response to therapy.
Degree-Granting Education |
| 1991 | University of Texas Southwestern Medical Center, Dallas, TX, PHD, Microbiology |
| 1985 | University of Texas, Austin, TX, BA, with Honors, Microbiology |
Postgraduate Training |
| 1991-1994 | Research Fellowship, Genetics, Howard Hughes Medical Institute, Duke University Medical Center, Durham, NC, Dr. Joseph R. Nevins |
Academic Appointments
| 2007 | Commendation, Graduate School of Biolmedical Sciences |
| 2000-2003 | Faculty Scholar Award, UT MD Anderson Cancer Center |
| 1996-1998 | Junior Faculty Scholar, American Cancer Society |
| 1991-1994 | Postdoctoral Fellowship, American Cancer Society |
Peer-Reviewed Original Research Articles |
| 1. | 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, 8/2008. PMID: 18469863. |
| 2. | Hong SK, Paulson QX, Johnson DG. E2F1 and E2F3 activate ATM through distinct mechanisms to promote E1A-induced apoptosis. Cell Cycle 7(3):391-400, 2/2008. PMID: 18235226. |
| 3. | Russell JL, Weaks RL, Berton TR, Johnson DG. E2F1 suppresses skin carcinogenesis via the ARF-p53 pathway. Oncogene 25(6):867-76, 2/2006. PMID: 16205640. |
| 4. | 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, 1/2006. PMCID: PMC1345703. |
| 5. | 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, 1/2006. PMID: 16340309. |
| 6. | 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, 4/2005. PMID: 15735727. |
© 2009 The University of Texas M. D. Anderson Cancer Center
