Staff Fellow — Genetic and Molecular Toxicology

Meagan Myers, Ph.D.
(870) 543-7121
NCTRResearch@fda.hhs.gov  

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About  |  Publications  |  Lab Members

Background

Dr. Meagan Myers received her B.S. degree in biology with a concentration on molecular biotechnology from the University of Arkansas at Little Rock in 2000. For her doctoral research, she developed a method for the quantification of mtDNA copy number to assess mtDNA depletion after in vivo exposure to potential mitochondrial toxicants. She received her Ph.D. in interdisciplinary toxicology from the University of Arkansas for Medical Sciences. In 2006, she joined NCTR as a staff fellow in the Division of Genetic and Molecular Toxicology where she is a key researcher in the “Oncomutations as Biomarkers of Cancer Risk” program. Dr. Myers has served on the NCTR Institutional Animal Care and Use Committee since 2011. She has received numerous NCTR and FDA honors and awards for her work, including:

• NCTR “Directors Award”
• NCTR “Outstanding Service Award”
• FDA “Group Recognition Award”
• FDA “Outstanding Service Award”

Research Interests

Dr. Myers’ research focuses on developing somatic hotspot-point mutations as quantitative biomarkers of cancer risk. Utilizing the highly-sensitive, Allele-specific Competitive Blocker PCR method, she has quantified levels of hotspot cancer-driver mutations, such as those found in KRAS, in various human tissues and tumors. Her research interests include defining normal and pathological levels of cancer-relevant mutations, with the ultimate goal of understanding how low-frequency mutant subpopulations in tumors may contribute to acquired resistance to cancer therapies. 

Detection of cancer-driver mutant subpopulations and their potential impact on molecularly-targeted therapy
Tumor mutations are being used as predictive biomarkers of therapeutic response to select the most effective treatments for individual cancer patients. Currently, this is being done without sufficient characterization of relevant oncogene mutations as quantitative biomarkers. Sensitive and quantitative analyses of prevalent cancer-driver mutations is necessary to understand the role of mutant-tumor subpopulations in patient response and to develop effective strategies to ensure such mutations do not lead to acquired drug resistance and/or relapse. Dr. Myers work has led to several significant findings, including:

• low-frequency cancer-driver point mutations are prevalent in the DNA of normal tissues
• many tumors carry subpopulations of these cancer-driver mutations that would go undetected by standard mutation detection techniques (e.g. DNA sequencing)
• these mutations co-occur frequently in normal and tumor samples.

Oncomutational profile of triple-negative breast cancer
It is recognized that breast cancer is a heterogeneous disease, with respect to clinical features, prognosis, and response to cancer therapies. Yet, relatively little is known regarding the frequency and potential role of subclonal cancer-driver mutations in the different subtypes of breast cancer, including triple-negative breast cancer. Dr. Myers is the principal investigator of an FDA Office of Women’s Health (OWH)-funded project that aims to quantify cancer-driver mutations in breast-cancer subtypes to help direct personalized-medicine approaches to treat breast cancer, including triple-negative breast cancer. This project has received additional OWH funding to expand the racial diversity of the study to include additional ductal carcinomas from African-American women.

Mutation Detection applications of Droplet Digital PCR
Genetic testing plays a major role in the diagnosis, treatment, and management of cancer. The value of cancer-driver mutations in precision medicine, as both prognostic and predictive biomarkers, is evident for multiple cancer types. Given the intratumor heterogeneity present in many tumor types, however, accurately detecting and quantifying these specific cancer-driver mutations is challenging. Droplet Digital PCR (ddPCR), which quantifies target nucleic acids in a water-in-oil emulsion using microfluidics, has been marketed as an ultra-sensitive platform to accurately quantify low-frequency cancer-driver mutations in human-tumor DNA and DNA from liquid biopsies. The purported sensitivity and ease of use could make ddPCR a viable candidate for application as an in vitro diagnostic in the clinical setting, however, pre-analytical and analytical questions regarding the use of ddPCR have been raised. To address some of these concerns, Dr. Myers received protocol approval to assess the utility and analytical performance of ddPCR for detecting somatic-cancer variants through concordance to other methods such as next-generation sequencing and ACB-PCR.

Professional Societies/National and International Groups

Environmental Mutagenesis and Genomics Society
Councilor
2016 – Present

Women in the Environmental Mutagenesis and Genomics Society
Chair
2014 – Present

Young Scientist Award Committee
Member
2015 – Present

Education, Student and New Investigator Affairs Committee
Member
2009 – Present

South Central Chapter of the Society of Toxicology
Councilor
2010 – 2012

Annual Meeting Organization Committee
Member
2012

Select Publications

Publication titles are linked to text abstracts on PubMed.

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, 18:253-263.
 

Targeted Therapies with Companion Diagnostics in the Management of Breast Cancer: Current Perspectives.
Myers M.
Pharmgenomics Pers Med. 2016, 9:7-16.
 

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 Level Above Normal Thyroid.
Myers M., McKim K., and Parsons B.
Mol Carcinog. 2014, 53:159-167.
 

ACB-PCR Quantification of Somatic Oncomutation.
Myers M., McKinzie P., Wang Y., Meng F., and Parsons B.
Methods in Molecular Biology. 2014, 1105:345-363.
 

Mutagenesis and Genetic Toxicology.
Moore MM, Myers MB, Heflich RH.
Principles of Toxicology: Environmental and Industrial Applications. 2014; 3: 235-258.
 

Temporal Changes in K-ras Mutant Fraction in Lung Tissue of Big Blue B6C3F(1) 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, 136:26-38.
 

Personalized Cancer Treatment and the Myth of KRAS Wild-Type Colon Tumors.
Parsons B. and Myers M.
Discovery Medicine. 2013, 15:259-267.
 

Assessment of K-Ras Mutant Frequency and Micronucleus Incidence in the Mouse Duodenum Following 90-Days of Exposure to Cr(VI) in Drinking Water.
O'Brien T., Ding H., Suh M., Thompson C., Parsons B., Harris M., Winkelman W., Wolf J., Hixon J., Schwartz A., Myers M., Haws L., and Proctor D..
Mutat Res. 2013; 754:15-21.
 

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, 53:495-504.
 

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.
 

P53 Codon 271 CGT to CAT Mutant Fraction Does Not Increase in Nasal Respiratory and Olfactory Epithelia of Rats Exposed to Inhaled Naphthalene.
Meng F., Wang Y., Myers M., Wong B., Gross E., Clewell H., Dodd D., and Parsons B.
Mutat Res. 2011, 721:199-205.
 

Oncomutations as Biomarkers of Cancer Risk.
Parsons B., Myers M., Meng F., Wang Y., and McKinzie P.
Environ Mol Mutagen. 2010, 51:836-850.
 

Using Phix174 DNA as an Exogenous Reference for Measuring Mitochondrial DNA Copy Number.
Myers M., Mittelstaedt R., and Heflich R.
Biotechniques. 2009, 47:867-869.
 

Accumulation of Point Mutations in Mitochondrial DNA of Aging Mice.
Khaidakov M., Heflich R., Manjanatha M., Myers M., and Aidoo A.
Mutat Res. 2003, 526:1-7.
 

Lab Members

Contact information for all lab members:
(870) 543-7121
NCTRResearch@fda.hhs.gov  

Malathi Banda, Ph.D.
ORISE Postdoctoral Fellow

Kelly Harris, Ph.D.
ORISE Postdoctoral Fellow

Karen L. McKim, B.S.
Chemist

Barbara L. Parsons, Ph.D.
Research Microbiologist