The Shields laboratory pursues basic science discovery that improve clinical medicine. Our lab is composed of faculty, postdoctoral fellows, graduate and other students and staff with diverse training in medicine, tumor biology, epidemiology, biostatistics, and bioinformatics and toxicology. We conduct molecular epidemiology studies from the laboratory to the community. Our laboratory is especially suited for the physician-scientist in training, the postdoctoral researcher and students interested in the causes of cancer, developing tests to determine who is at greatest risk, and developing prevention strategies. Our research focuses on breast cancer and tobacco use.
The Shields Lab began in 1990 at the National Institute of Health when Dr. Shields was a senior clinical investigator and section chief with the National Cancer Institute. The lab moved to Georgetown University in 2000 when Dr. Shields and his research group expanded his studies while he also served as professor of medicine and oncology, vice-chair for the Department of Oncology, associate director for cancer control and population sciences, and deputy director of the Lombardi Comprehensive Cancer Center. In 2011, Shields’ research group moved from Georgetown University to Ohio State where Dr. Shields became deputy director of The Ohio State University Comprehensive Cancer Center. Dr. Theodore Brasky (assistant professor) was recruited to join this group in 2013 upon completing his epidemiology postdoctoral fellowship under Dr. Emily White at the Fred Hutchinson Cancer Center.
Dr. Shields' research focuses on gene-environment interactions for breast and lung cancer risk, with an emphasis on toxicology and carcinogenesis. The laboratory component of his research develops new biomarkers of cancer risk related to diet and lifestyle.
In breast cancer research, Dr. Shields has received funding from several foundation and federal government sources, e.g., Avon Foundation, Komen Foundation, National Cancer Institute (R01) and Department of Defense (Idea Awards and Center of Excellence). A major initiative led by Dr. Shields was a Breast Cancer Center of Excellence, initially funded by the Department of Defense. This was a multi-investigator and multidisciplinary approach to understanding the roles that alcohol drinking and nutrition play in breast cancer, as a model for the causes of cancer. At Georgetown, the Shields lab established a study of healthy women with no history of breast cancer who were undergoing reduction mammoplasty. The researchers studied the effects in the breast of nutrition, alcohol drinking and other lifestyle factors using various biomarkers such as nutrients, hormone like adipokines and IGFs, and markers of differentiation and proliferation. Building upon their finding for the presence of p16 hypermethylation in the breast tissue of 31 percent of women with no history of breast cancer, the Shields Lab found that the risk for p16 hypermethylation increased for women with lower breast folate, higher alcohol drinking and a single nucleotide polymorphism (SNP) in the methylenetetrahydrofolate dehydrogenase 1 gene. Having p16 tumor-promoter methylation was associated with reduced protein expression, indicating a biological consequence to the hypermethylation. Separately, the Shields Lab has been assessing the relationship of blood to breast tissue hormone levels as a way to assess the validity of epidemiology studies that use blood levels for risk prediction. For insulin growth factor 1 and insulin growth factor binding protein-3, there was no relation, and only modest correlations for leptin and adiponectin, which were better for normal-weight women rather than obese women. The lab did, however, find that BMI and race were predictive of leptin levels, while oral contraceptive use and smoking were predictive of adiponectin levels. They also found that a SNP in the LEP gene (A19G) affected the ratio of breast leptin to adiponectin. At Ohio State, the lab is collaborating with Drs. Soledad Fernandez (Department of Medicine), Gustavo Leone (Department of Molecular Genetics) and Kun Huang (Department of Biomedical Informatics) on this study. This work is also being expanded to identify global changes in methylation, gene and microRNA expression using the Genomics Shared Resource. The group has identified microRNAs that are altered depending on various breast cancer risk factors. Lastly, a new study of women undergoing reduction mammoplasty and women with breast cancer is being conducted in conjunction with Drs. Lisa Yee (Department of Surgery) and Michael Miller (Department of Plastic Surgery).
The Shields group has continued collaborations with Dr. Jo Freudenheim at the University of Buffalo and the Roswell Park Cancer Institute, Dr. Christine Ambrosone at Roswell Park Cancer Institute, and Dr. Catalin Marian at the University of Medicine and Pharmacy of Timisoara in the above studies showing that genome-wide methylation status differs by race and breast tumor type. The Shields lab also has been continuing our longstanding collaboration for a population-based case-control study of breast cancer that has yielded over 40 publications discovering the causes of breast cancer and those with increased risk due to lifestyle and other causes, including genetics. They are continuing studies of the Western New York Exposures and Breast Cancer Study, and they recently have shown that increased nausea and vomiting during pregnancy decreases breast cancer risk, that a SNP in BRCA1 increases the risk of triple-negative breast cancer, and that life-time physical activity improves breast cancer survival.
In tobacco research, the Shields group has been studying DNA damage, DNA repair and other effects of tobacco smoke in humans, showing the relationship of genetics to DNA damage and identifying genes relating to nicotine dependence and tobacco use. They also have studied the toxic effects of smoke in the laboratory and how this affects smokers. Most recently, Dr. Shields and the research group has been studying the effects of smoking on metabolomics and changes in gene expression. A major initiative that was led by Dr. Shields’ was a multi-institutional NCI contract for the development of methods to study new tobacco products. These efforts standardized methods to study tobacco exposure and effect, led to numerous comprehensive publications reviewing best practices for studying tobacco and identifying research gaps, developed a framework for studying tobacco products in support of the Food and Drug Administration, and conducted several human studies (clinical trials and cross-sectional studies) to establish a biorepository for the development and validation of new biomarkers of cancer risk.
At Ohio State, he and Dr. Mary Ellen Wewers (College of Public Health) co-lead a Tobacco Center of Regulatory Science – a five- year, 18 million dollar co-lead grant from the National Cancer Institute. This grant established the OSU Center of Excellence in Regulatory Tobacco Science (OSU-CERTS), which is one of 14 Centers of Regulatory Science (TCORS) established as part of an NIH/FDA collaboration designed to generate research regarding the regulation of tobacco products, to protect public health and to train the next generation of tobacco regulatory scientists. Along with serving as co-PI of the grant, Dr. Shields is directors of four projects of OSU-CERTS. His project, closely linked with another project directed by Dr. Amy Ferketich (College of Public Health), focuses on the dual use of cigarette smoking and smokeless tobacco among adolescent males in Ohio. Researchers hope to understand tobacco use, the way these affect how quickly adolescents and young adults develop addictions, what their toxic exposures are, and the genetics that make them more susceptible to addiction. Information from this large study will help FDA decision-making about what restrictions, if any, to place on the marketing of tobacco products in the context of youth initiation and dual use. It will also assist with the regulation of tobacco marketing and promotion, with the decision to target health-related communications to adolescents susceptible to dual use, with the development of product standards related to exposures and flavorings, and with the development of better tests to identify tobacco related health risks.
Theodore Brasky, PhD, Assistant Professor
Alek Erdel, Clinical Research Assistant
Sahar Kamel, Clinical Research Assistant
Quentin Nickerson, Research Assistant
Sarah Reisinger, MPH, MCHES, Program Director
Min-Ae Song, PhD, Postdoc
Carmine Sonzone, PhD Student
Daniel Weng, PhD, Research Scientist
Kevin Ying, Graduate Research Assistant