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  1. Science & Research (NCTR)

Page McKinzie Ph.D.

Research Microbiologist — Genetic and Molecular Toxicology

Page McKinzie
Page McKinzie, Ph.D.

(870) 543-7391
NCTRResearch@fda.hhs.gov  

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About  |  Publications  |  Lab Member


Background

Dr. Page McKinzie received her B.A. degree in chemistry with a minor in biology from Huntingdon College in Alabama. She continued her studies at the University of Alabama at Birmingham (UAB) and earned her Ph.D. in cellular and molecular biology. Her graduate work encompassed both studies on oxygen free radical production in whole animals and on developing liposomal drug-delivery systems for the treatment of oxygen free radical-induced injury.  Following graduate training, Dr. McKinzie continued to work on developing drug-delivery systems in the Gene Therapy Program at the UAB, with a focus on developing attenuated adenoviral vectors to deliver gene therapeutics to human papillomavirus (HPV)-infected cells in the effort to treat HPV-related human cervical cancers. 

Dr. McKinzie began her career at NCTR developing a specialized polymerase chain reaction (PCR) method for detecting and quantifying cancer-related mutations at the sensitivity of 1 mutant out of 100,000 normal copies of the gene. This method, called allele-specific competitive blocker PCR (ACB-PCR) has proven useful over the years for collecting data on cancer-gene mutations. However, with the advent of next generation sequencing (NGS), the quantification of these mutations can be expanded to cover many mutations simultaneously. This will increase the throughput of cancer-gene mutation data from various biological sources. 

Dr. McKinzie is now actively conducting research using NGS methods to provide a new avenue for quantifying these mutations at high sensitivity. She is also working on discovering rodent gene mutations that are relevant and appropriate for human extrapolation. These research activities incorporate innovative ways to prepare samples for analysis and equally innovative ways to analyze the data (bioinformatics) to be accurate and informative. These efforts will provide the information necessary to confidently extrapolate from in vivo, in vitro, and ex vivo test systems to true cancer risk assessment for humans.

Research Interests

Gene mutations that are involved in cancer development occur in a small number of cells before they are numerous enough to be observed as a tumor. The early detection in human health care and the ability to use rodent models for human-cancer risk assessment both rely on the ability to quantify these few mutant cells from otherwise normal appearing samples. Additionally, sensitive quantification is also needed for accurately determining the composition of tumors, which are inherently heterogeneic. Tumors contain cooperating groups of cells, each with different mutations that are important for the growth, persistence, and metastasis of the cancer. The heterogeneity of tumors can also lead to a relapse after targeted therapy for single mutations, which makes the development of a high-throughput high-sensitivity mutation assay a priority for human health.

Dr. McKinzie is developing new methods for quantifying gene mutations that are involved in cancer formation by leveraging massively parallel sequencing to provide quantitative data for many gene mutations from each of many samples simultaneously. These methods require implementation of error-corrected sequencing methods that begin with proper handling of the sample, library preparation, and proper processing of the data that is produced from the sequencing run. Dr. McKinzie’s laboratory is focused on developing molecular biology and bioinformatics methods to produce highly accurate quantitation of cancer-causing mutations to greatly improve human-cancer risk assessment from various preclinical models.

Professional Societies/National and International Groups

Environmental Mutagenesis and Genomics Society
Member
2012 – Present 

Midsouth Computational Biology and Bioinformatics Society
Member
2016 – Present

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Select Publications

Publication titles are linked to text abstracts on PubMed.

Whole Genome Sequencing of Mouse Lymphoma L5178Y-3.7.2C (TK+/-) Reveals Millions of Mutations and Genetic Markers.disclaimer icon
McKinzie PB and Revollo JR.
Journal/Mutat Res Genet Toxicol Environ Mutagen. 2017; 814:1-6
 

Whole Genome and Normalized Mrna Sequencing Reveal Genetic Status of TK6, WTK1, and NH32 Human B-Lymphoblastoid Cell Lines.
Revollo J, Petibone DM, McKinzie P, Knox B, Morris SM, Ning B, Dobrovolsky VN.
Journal/Mutat Res Genet Toxicol Environ Mutagen. 2016; 795:60-9
 

Accumulation of K-ras Codon 12 Mutations in the F344 Rat Distal Colon Following Azoxymethane Exposure.
McKinzie P, Parsons B.
 

Oncomutations as Biomarkers of Cancer Risk.
Parsons B, Myers M, Meng F, Wang Y, McKinzie P.
Journal/Environ Mol Mutagen. 2010; 51:836-50.
 

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, Parsons B.
Journal/Mutagenesis. 2006; 21:391-7.
 

Allele-Specific Competitive Blocker-PCR Detection of Rare Base Substitution.
Parsons B, McKinzie P, Heflich R.
Journal/Methods Mol Biol. 2005; 291:235-45.
 

Detection of Rare K-ras Codon 12 Mutations Using Allele-Specific Competitive Blocker PCR.
McKinzie P, Parsons B.
Journal/Mutat Res. 2002; 517:209-20.
 

Prospects for Applying Genotypic Selection of Somatic Oncomutation to Chemical Risk Assessment.
McKinzie P, Delongchamp R, Heflich R, Parsons B.
Journal/Mutat Res. 2001; 489:47-78.
 

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Lab Member

Michelle Bishop
Support Scientist
(870) 543-7391
NCTRResearch@fda.hhs.gov  

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Contact Information
Page McKinzie
(870) 543-7391
Expertise
Approach