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David L. Mitchell, Ph.D.

Present Title & Affiliation

Primary Appointment

Professor, Department of Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Smithville, TX

Research Interests

The overall objective of Dr. Mitchell's research is to understand the molecular and biological responses of cells to DNA damage resulting from solar ultraviolet (UV) radiation. From these studies, the aim is to better understand the molecular basis of sunlight-induced skin cancer, particularly melanoma. Several aspects of this problem are currently under study. One major effort is to investigate the etiology of melanoma using fish models and human cell lines.  The lab has used the Xiphophorus (platyfish/swordtail) fish model to examine the efficacy of UVA and UVB radiation on melanoma. The results of these studies showed that UVB is an absolute requirement for melanoma formation; UVA cannot by itself induce melanoma. Moreover, reversal of the two major photoproducts in DNA by photoenzymatic repair inhibits melanoma, indicating that the presence of these lesions immediately after sunlight exposure is essential for melanoma formation.  Based on these data, the lab is developing an "after-sun" treatment that uses DNA repair enzymes to eliminate the DNA damage that causes melanoma in humans.  To pursue these studies, the lab is also developing a new UV-inducible melanoma model in zebrafish in which the human BRAFV600E mutant gene has been transgenically incorporated.  By knocking down different fish repair enzymes in this new model, the type(s) of damage and the critical temporal window associated with melanoma initiation can be determined and the practicality of an after-sun treatment evaluated. Another focus in the Mitchell lab is on behavioral and hormonal regulation of the oncogenes currently known to affect melanoma in fish, and the identification of hormonal pathways (e.g., androgen and estrogen receptors) that may crosstalk with genetic and epigenetic pathways to allow melanoma promotion and progression.  The Mitchell lab is also interested in understanding how geographical and latitudinal differences in UVB affect aquatic organisms ranging from viruses and bacteria to fish.  The lab has been involved in several multi-investigator studies of the effects of environmental factors on the UV response across a broad trophic spectrum of planktonic organisms in fresh water lakes, streams and marine organisms, particularly in Antarctica. 

Office Address

The University of Texas MD Anderson Cancer Center
1808 Park Road 1C
P.O. Box 389
Smithvlle, TX 78957
Phone: (512) 237-9474

Education & Training

Degree-Granting Education

1988 The University of Texas at Austin, Austin, TX, PHD, Molecular Biology
1980 The University of Texas Health Science Center at Houston, Houston, TX, MS, Molecular Biology
1975 The University of Texas at Austin, Austin, TX, BS, Zoology

Postgraduate Training

1/1988-1/1990 Alexander Hollaender Postdoctoral Fellow, University of California, San Francisco, CA


Administrative Appointments/Responsibilities

Director, Community Outreach and Education Program, The University of Texas MD Anderson Cancer Center, Smithville, TX, 2011-present

Selected Publications

Peer-Reviewed Original Research Articles

1. 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, 6/15/2014. e-Pub 4/16/2014. PMCID: PMC4083823.
2. Meador JA, Baldwin AJ, Pakulski JD, Jeffrey WH, Mitchell DL, Douki T. The significance of the Dewar valence photoisomer as a UV radiation-induced DNA photoproduct in marine microbial communities. Environ Microbiol 16(6):1808-20, 6/2014. e-Pub 3/5/2014. PMID: 24517516.
3. Yang K, Boswell M, Walter DJ, Downs KP, Gaston-Pravia K, Garcia T, Shen Y, Mitchell DL, Walter RB. UVB-induced gene expression in the skin of Xiphophorus maculatus Jp 163 B. Comp Biochem Physiol C Toxicol Pharmacol 163:86-94, 6/2014. e-Pub 2/17/2014. PMCID: PMC4067948.
4. Mitchell DL, Fernandez AA, Garcia R, Paniker L, Lin K, Hanninen A, Zigelsky K, May M, Nuttall M, Lo HH, Person MD, Earley R. Acute exposure to ultraviolet-B radiation modulates sex steroid hormones and receptor expression in the skin and may contribute to the sex-bias of melanoma in a fish model. Pigment Cell Melanoma Res 27(3):408-17, 5/2014. e-Pub 2/3/2014. PMID: 24406016.
5. Sproul CD, Mitchell DL, Rao S, Ibrahim JG, Kaufmann WK, Cordeiro-Stone M. Cyclobutane Pyrimidine Dimer Density as a Predictive Biomarker of the Biological Effects of Ultraviolet Radiation in Normal Human Fibroblast. Photochem Photobiol. e-Pub 10/2013. PMID: 24148148.
6. Mitchell DL, Paniker L, Godar D. Nucleotide excision repair is reduced in oral epithelial tissues compared with skin. Photochem Photobiol 88(4):1027-32, Jul-Aug, 7/2012. e-Pub 6/2012. PMCID: PMC3437763.
7. Fernandez AA, Paniker L, Garcia R, Mitchell DL. Recent advances in sunlight-induced carcinogenesis using the Xiphophorus melanoma model. Comp Biochem Physiol C Toxicol Pharmacol 155(1):64-70, 1/2012. e-Pub 3/2011. PMCID: PMC3164944.
8. 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, 3/2011. e-Pub 10/2010. PMCID: PMC3045616.
9. Mitchell DL, Fernandez AA. Different types of DNA damage play different roles in the etiology of sunlight-induced melanoma. Pigment Cell Melanoma Res 24(1):119-24, 2/2011. e-Pub 10/2010. PMID: 20955242.
10. 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):19308-15, 6/2010. e-Pub 4/2010. PMCID: PMC2885209.
11. Mitchell DL, Fernandez AA, Nairn RS, Garcia R, Paniker L, Trono D, Thames HD, Gimenez-Conti I. Ultraviolet A does not induce melanomas in a Xiphophorus hybrid fish model. Proc Natl Acad Sci U S A 107(20):9329-34, 5/2010. e-Pub 5/2010. PMCID: PMC2889042.
12. Tucker AJ, Williamson CE, Rose KC, Oris JT, Connelly SJ, Olson MH, Mitchell DL. Ultraviolet radiation affects invasibility of lake ecosystems by warm-water fish. Ecology 91(3):882-90, 3/2010. PMID: 20426345.
13. Mitchell DL, Paniker L, Sanchez G, Bella Z, Garaczi E, Szell M, Hamid Q, Kemeny L, Koreck A. Molecular response of nasal mucosa to therapeutic exposure to broad-band ultraviolet radiation. J Cell Mol Med 12(5):1-10, 1/2010. e-Pub 7/2008. PMID: 18671762.
14. Zeng Z, Richardson J, Verduzco D, Mitchell DL, Patton EE. Zebrafish have a competent p53-dependent nucleotide excision repair pathway to resolve ultraviolet B-induced DNA damage in the skin. Zebrafish 6(4):405-15, 12/2009. PMCID: PMC2804931.
15. Lange SS, Mitchell DL, Vasquez KM. High mobility group protein B1 enhances DNA repair and chromatin modification after DNA damage. Proc Natl Acad Sci U S A 105(30):10320-5, 7/2008. PMCID: PMC2492475.
16. Nijhof JG, van Pelt C, Mulder AA, Mitchell DL, Mullenders LH, de Gruijl FR. Epidermal stem and progenitor cells in murine epidermis accumulate UV damage despite NER proficiency. Carcinogenesis 28(4):792-800, 4/2007. PMID: 17127714.
17. Britt AB, Chen JJ, Wykoff D, Mitchell DL. A UV-sensitive mutant of Arabidopsis defective in the repair of pyrimidine-pyrimidinone(6-4) dimers. Science 261(5128):1571-4, 9/1993. PMID: 8372351.
18. Karentz D, Cleaver JE, Mitchell DL. Cell survival characteristics and molecular responses of antarctic phytoplankton to UV radiation. J Phycol 27(3):326-41, 6/1991.
19. Mitchell DL, Clarkson JM. The development of a radioimmunoassay for the detection of photoproducts in mammalian cell DNA. Biochim Biophys Acta 655(1):54-60, 8/1981. PMID: 7260090.

Invited Articles

1. Mitchell DL, Fernandez A. The photobiology of melanocytes modulates the impact of UVA on sunlight-induced melanoma. Photochem Photobiol Sci 11(1):69-73, 1/2012. e-Pub 9/2011. PMID: 21887451.
2. Patton EE, Mitchell DL, Nairn RS. Genetic and environmental melanoma models in fish. Pigment Cell Melanoma Res 23(3):314-37, 6/2010. e-Pub 3/2010. PMCID: PMC2881310.
3. Mitchell DL, Brooks B. Antibodies and DNA photoproducts: applications, milestones and reference guide. Photochem Photobiol 86(1):2-17, 1/2010. e-Pub 12/2009. PMID: 20003175.
4. Mitchell DL, Karentz D. Molecular and biological responses of Antarctic phytoplankton to ultraviolet radiation. Antarctic J of the U.S. 25:174-5, 1990.
5. Mitchell DL, Nairn RS. The biology of the (6-4) photoproduct. Photochem Photobiol 49(6):805-19, 6/1989. PMID: 2672059.
Other Articles
1. Mitchell DL. Revisiting the photochemistry of solar UVA in human skin. Proc Nat Acad Sci USA 103(37):13567-8, 9/2006. PMCID: PMC1564261.

Book Chapters

1. Berton TR, Mitchell DL. Quantification of DNA photoproducts in mammalian cell DNA using radioimmunoassay. In: Methods Mol Biol. 920, 177-87, 2012. ISBN: 22941604.
2. Cleaver JE, Mitchell DL. Ultraviolet radiation carcinogenesis. In: Cancer Medicine. 18, 8th. Ed(s) WK Hong, RC Bast, W Hait, DW Kufe, RE Pollock, RR Weichselbaum, JF Holland, E Frei III. BC Decker, Inc. Hamilton-London, 262-269, 2009.
3. Mitchell DL, Ghosh R. Oxidative DNA damage and promoter function. In: Oxidative Damage to Nucleic Acids. Molecular Biology Intelligence Unit, Chapter 7. Ed(s) Evans MD, Cooke MS. Landes Bioscience: Leicester, UK, 2007.
4. Cleaver JE, Mitchell DL. Ultraviolet radiation carcinogenesis. In: Holland Frei Cancer Medicine. Chapter 17, 7. Ed(s) Kufe DW, Frei III E, Holland JV, Weichselbaum RR, Pollock RE, Bast Jr RC, Hong WK, Hait WN. BC Decker, Inc. Columbia, 2006.

Grant & Contract Support

Title: MD Anderson Science Park Summer Program in Cancer Research
Funding Source: NIH/NCI
Role: Principal Investigator-MDACC
Duration: 8/11/2014 - 7/31/2019

Last updated: 11/7/2014