Research Microbiologist — Division of Genetic and Molecular Toxicology
Barbara Parsons, Ph.D.
Dr. Barbara Parsons has nearly forty years of experience and expertise applying molecular biology techniques to a variety of research areas. Dr. Parsons studied biology at the State University of New York at Binghamton and received her B.S. degree in biology in 1980. From 1980-1982, she worked as a technician under the supervision of Dr. Richard J. Roberts at Cold Spring Harbor Laboratory, where she participated in sequencing the adenovirus-2 genome. As a participant in its Interdisciplinary Program in Genetics, Dr. Parsons conducted research on the telomere sequences of Orthopoxviruses and obtained her Ph.D. in microbiology and immunology from Duke University in 1988. She conducted research in plant molecular biology at the Beltsville Agricultural Research Center from 1988 to 1992. Specifically, she studied the plant hormone, ethylene, and its impact on gene expression and tomato fruit ripening. Dr. Parsons worked as a research associate at the University of Arkansas at Little Rock from 1992 to 1994. She joined NCTR as an Oak Ridge Institute for Science and Education (ORISE) postdoctoral fellow in 1994. Dr. Parsons has been a research microbiologist serving as a principal investigator in the NCTR Division of Genetic and Molecular Toxicology since 2002.
At NCTR, Dr. Parsons developed a highly-sensitive, allele-specific competitive blocker-PCR method (ACB-PCR). This method has been used to quantify specific hotspot-point mutations in oncogenes and tumor-suppressor genes at very low frequencies (3 mutants in a background of 300,000 wild-type alleles). Dr. Parsons and colleagues have developed a unique research program around the use of ACB-PCR. The goals of this program are to improve methods for assessing the carcinogenic potential of human exposures and developing knowledge that will advance the field of personalized medicine.
Methods for assessing the carcinogenic potential of new drug entities, food and drug contaminants, or other chemical exposures are absolutely necessary. Unfortunately, current methods are costly, time-consuming, and the application of rodent testing data to human-health protection is imprecise. Therefore, Dr. Parsons is collaborating with a group of scientists at NCTR, who are working to develop new approaches and novel biomarkers to improve carcinogenicity safety assessment. At the core of this work is the idea that hotspot cancer-driver mutations (CDMs) will be relevant and sensitive biomarkers of chemical carcinogenic effect and can be monitored as part of carcinogenic risk assessment.
Dr. Parsons’s group has developed proof-of-principle that following short-term exposures to model mutagenic carcinogens, ACB-PCR detect the induction of hotspot-point mutations (e.g., mutations in KRAS, HRAS, and TP53) in DNA isolated from tissues of exposed rodents. In fact, this work suggests that CDMs are highly-sensitive biomarkers of carcinogenic effect. The possibility that such mutations can also serve as reporters of chemicals considered to be non-genotoxic, cancer “promoters” (rather than genotoxic “initiators”) remains an important question to be investigated in the future.
Advancing the field of Personalized Medicine is another goal being addressed by Dr. Parsons and her lab at NCTR. Specifically, they have been developing the knowledge necessary to utilize hotspot CDMs as biomarkers of cancer susceptibility and therapeutic response in the clinical setting. Dr. Parsons and colleagues used ACB-PCR to quantify levels of KRAS and PIK3CA hotspot-point mutations in normal human tissues (breast, colon, lung, and thyroid), as well as in cancers that develop from those organs. This work demonstrated that these hotspot CDMs occur at remarkably high levels in some tissues (e.g., PIK3CA H1047R in breast tissue) and their organ-specific prevalence mirrors the reported prevalence of the same mutations detected in tumors by DNA sequencing.
ACB-PCR analyses of hotspot CDMs, in a limited number of genes (KRAS, HRAS, PIK3CA, and BRAF), showed that low-frequency mutant-tumor subpopulations are remarkably common. Based on their analyses of KRAS G12D and G12V in colon and lung adenocarcinomas, for example, Dr. Parsons and colleagues predicted that virtually all colon and lung tumors will carry a KRAS mutation at some level. This observation is consistent with the acquired resistance that develops predictably in the majority of colon- and lung-cancer patients treated with inhibitors of Epidermal Growth Factor Receptor (EGFR) (due to the pre-treatment existence of tumor subpopulations carrying KRAS or other CDMs). Combination treatments with multiple molecularly targeted anti-cancer drugs may be necessary to circumvent acquired resistance. This means models are needed to identify the most promising combination therapies for subsequent clinical evaluation. Given this need, Dr. Parsons’s group recently developed a 3D lung-tumor organoid model and showed that, under conditions of treatment an EGFR inhibitor (erlotinib), it could detect the outgrowth of mutant-tumor subpopulations known to cause resistance to treatment in the clinical setting. Thus, this model may be useful for identifying efficacious combination therapies that prevent the outgrowth of resistant-causing mutant subpopulations.
Most recently, Dr. Parson’s lab has begun developing error-corrected Next Generation Sequencing (NGS) methods to: 1) enable the analysis of a larger battery of hotspot CDMs. 2) compare the sensitivities of NGS, ddPCR, and ACB-PCR, and 3) identify which rodent CDMs have tissue-specific properties that mirror human CDMs. The intent of this work is to improve the translatability of carcinogenicity testing in rodents to human cancer-risk assessment.
Professional Societies/National and International Groups
American Association for Cancer Research
2006 – Present
Environmental Mutagenesis and Genomics Society
2013 – 2016
Chair, Awards and Honors Committee
2013 – 2014
1995 – Present
Society of Toxicology
2004 – Present
South Central Chapter of the Society of Toxicology
2012 – 2013
2000 – Present
Publication titles are linked to text abstracts on PubMed.
Variation in Organ‐Specific PIK3CA and KRAS Mutant Levels in Normal Human Tissues Correlates with Mutation Prevalence in Corresponding Carcinomas.
Parsons B., McKim K., and Myers M.
Environ Mol Mutagen. 2017, 58(7):466-476.
Breast Cancer Heterogeneity Examined by High-Sensitivity Quantification of PIK3CA, KRAS, HRAS, and BRAF Mutations in Normal Breast and Ductal Carcinomas.
Myers M., Banda M., McKim K., Wang Y., Powell M., and Parsons B.
Neoplasia. 2016, 18(4):253-63.
Quantification of Kras Mutant Fraction in the Lung DNA of Mice Exposed to Aerosolized Particulate Vanadium Pentoxide by Inhalation.
Banda M., McKim K., Haber L., MacGregor J., Gollapudi B., and Parsons B.
Mutat Res Genet Toxicol Environ Mutagen. 2015, 789-790:53-60.
Low-Frequency KRAS Mutations are Prevalent in Lung Adenocarcinomas.
Myers M., McKim K., Meng F., and Parsons B.
Personalized Medicine. 2015, 12:83-98.
A Subset of Papillary Thyroid Carcinomas Contain KRAS Mutant Subpopulations at Levels Above Normal Thyroid.
Myers M., McKim K., and Parsons B.
Mol Carcinog. 2014, 53(2):159-67.
Temporal Changes in K-Ras Mutant Fraction in Lung Tissue of Big Blue B6C3F₁ Mice Exposed to Ethylene Oxide.
Parsons B., Manjanatha M., Myers M., McKim K., Shelton S., Wang Y., Gollapudi B., Moore N., Haber L., and Moore M.
Toxicol Sci. 2013, 136(1):26-38.
Personalized Cancer Treatment and the Myth of KRAS Wild-Type Colon Tumors.
Parsons B. and Myers M.
Discov Med. 2013, 15(83):259-67.
KRAS Mutant Tumor Subpopulations Can Subvert Durable Responses to Personalized Cancer Treatments.
Parsons B. and Myers M.
Personalized Medicine. 2013, 10:191-199.
ACB-PCR Measurement of H-Ras Codon 61 CAA→CTA Mutation Provides an Early Indication of Aristolochic Acid I Carcinogenic Effect in Tumor Target Tissues.
Wang Y., Arlt V., Roufosse C., McKim K., Myers M., Phillips D., and Parsons B.
Environ Mol Mutagen. 2012, 53(7):495-504.
Hotspot Oncomutations: Implications for Personalized Cancer Treatment.
Myers M., Wang Y., McKim K., and Parsons B.
Expert Rev Mol Diagn. 2012, 12(6):603-20.
Oncomutations as Biomarkers of Cancer Risk.
Parsons B., Myers M., Meng F., Wang Y., and McKinzie P.
Environ Mol Mutagen. 2010, 51(8-9):836-50.
ACB-PCR Quantification of K-RAS Codon 12 GAT and GTT Mutant Fraction in Colon Tumor and Non-Tumor Tissue.
Parsons B., Marchant-Miros K., Delongchamp R., Verkler T., Patterson T., McKinzie P., and Kim L.
Cancer Invest. 2010, 28(4):364-75.
K-Ras Mutant Fraction in A/J Mouse Lung Increases as a Function of Benzo[A]Pyrene Dose.
Meng F., Knapp G., Green T., Ross J., and Parsons B.
Environ Mol Mutagen. 2010, 51(2):146-55.
K-RAS Mutation in the Screening, Prognosis and Treatment of Cancer.
Parsons B. and Meng F.
Biomark Med. 2009, 3(6):757-69.
Populations of P53 Codon 270 CGT to TGT Mutant Cells in SKH-1 Mouse Skin Tumors Induced by Simulated Solar Light.
Verkler T., Delongchamp R., Couch L., Miller B., Warbritton A., Mellick P., Howard P., and Parsons B.
Mol Carcinog. 2008, 47(11):822-34.
Many Different Tumor Types have Polyclonal Tumor Origin: Evidence and Implications.
Mutat Res. 2008, 659(3):232-47.
Simulated Solar Light-Induced P53 Mutagenesis in SKH-1 Mouse Skin: A Dose-Response Assessment.
Verkler T., Delongchamp R., Miller B., Webb P., Howard P., and Parsons B.
Mol Carcinog. 2008, 47(8):599-607.
ACB-PCR Measurement of K-Ras Codon 12 Mutant Fractions in Livers of Big Blue Rats Treated with N-Hydroxy-2-Acetylaminofluorene.
McKinzie P., Delongchamp R., Chen T., and Parsons B.
Mutagenesis. 2006, 21(6):391-7.
Levels of 4-Aminobiphenyl-Induced Somatic H-Ras Mutation in Mouse Liver DNA Correlate with Potential for Liver Tumor Development.
Parsons B., Beland F., Von Tungeln L., Delongchamp R., Fu P., and Heflich R.
Mol Carcinog. 2005, 42(4):193-201
Allele-Specific Competitive Blocker-PCR Detection of Rare Base Substitution.
Parsons B., McKinzie P., and Heflich R.
Methods Mol Biol. 2005, 291:235-45.
Prospects for Applying Genotypic Selection of Somatic Oncomutation to Chemical Risk Assessment.
McKinzie P., Delongchamp R., Heflich R., and Parsons B.
Mutat Res. 2001, 489(1):47-78.
Contact information for all lab members:
Kelly L. Harris, Ph.D.
ORISE Postdoctoral Fellow
Karen L. McKim, B.S.
Meagan B. Myers, Ph.D.
FDA Staff Fellow
- Contact Information
- Barbara Parsons
- (870) 543-7121
ExpertiseApproachDomainTechnology & DisciplineToxicology