Amanda Armijo, a postdoctoral fellow at MIT Professor John Essigmann’s group in the Department of Biological Engineering and Dr. James Fox’s group in the Division of Comparative Medicine, is studying the genotoxic signatures caused by environmental contaminants and how these mutations result in development of liver cancer. Specifically, her research focuses on the mutational patterns induced by the probable human carcinogen, N-nitrosodimethylamine (NDMA). NDMA is key contaminant of the Superfund site in Wilmington, MA, which for many years has contaminated the drinking water from several municipal wells. As part of the MIT Superfund Research Program, Amanda is utilizing a high-fidelity duplex consensus sequencing (DS) method to reveal early onset genetic signatures of environmental toxicant-driven human diseases that occur later in life. Identifying these mutational processes can inform strategies for Superfund site remediation as well as clinical genetic disease early-detection, intervention and prevention.
These experiments are being performed in transgenic C57Bl/6 mice that contain a reporter gene to enable a mutational assessment and high-fidelity sequencing of the changes in the DNA triplets in the reporter gene region. To accomplish this, the transgenic mice are treated with a carcinogenic regimen of NDMA and then liver DNA is analyzed 10 weeks post-exposure (prior to development of cancerous lesions) with DS to produce high resolution mutational spectra (HRMS). DS is a highly accurate method to identify rare, unique mutations present in a heterogenous genetic milieu. Mutational spectra patterns will also be identified in lesions that have fully developed into pathological cancer induced by NDMA. Gene-environment interactions that define inter-individual variations in sensitivity to NDMA will be identified using mutational patterns.
Amanda received her Bachelor’s degree in Microbiology, Immunology, and Molecular Genetics from UCLA. After working as a laboratory technician, she entered graduate school at UCLA in the department of Molecular and Medical Pharmacology where her work focused on the link between nucleotide metabolism and DNA replication stress responses. Her graduate work subsequently led to the preclinical development of a panel of small molecule inhibitors of deoxycytidine kinase as an anti-cancer therapeutic. Amanda successfully defended her dissertation and next attended Cornell University’s College of Veterinary Medicine, receiving a Doctor of Veterinary Medicine degree. Following completion of her DVM, Amanda completed an internship in Laboratory Animal Surgery and Medicine at Tufts University. She is happy to have found a program at MIT that combines her interests in both caring for laboratory animals and in performing important research that can positively impact human health. In her spare time, she enjoys sports, volunteering for spay/neuter clinics, cooking, and spending time with her family.
