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Three Investigators Receive Scientific Tenure

March 2013 - Linkage Newsletter

by Wendy Schneider-Levinson

NIH recently awarded scientific tenure to Mark Little, D.Phil., Radiation Epidemiology Branch, Sharon A. Savage, M.D., Clinical Genetics Branch, and Kai Yu, Ph.D., Biostatistics Branch.

Dr. Little joined DCEG in 2010 as a visiting senior scientist. Over the past two decades, he has specialized in analyzing cancer and cardiovascular disease risks in various irradiated populations and their offspring. Dr. Little has quantified radiation-cancer dose-response relationships at low and very low doses and has examined the likelihood of dose thresholds. His research has focused on breast, thyroid, and other solid cancers and hematopoietic malignancies in populations exposed to environmental, occupational, and medical sources of radiation. With his development of novel statistical methods for modeling these and other cancer risks, he created a disciplinary niche at the intersection of mathematical statistics and radiation biology. He also studied the risk of pediatric leukemia in relation to low-level radiation preconception, in utero, and postnatally among offspring of Japanese atomic bomb survivors and radiation workers. This research found no excess leukemia risk in the offspring of fathers exposed to low or moderate levels of radiation during the preconception period, alleviating public health concern about paternal preconception radiation.

Since joining DCEG, Dr. Little has been the lead statistician in the United Kingdom-NCI study of cancer risk following pediatric computed tomography exposure, and he has led the assessment of thyroid cancer risk in persons exposed in childhood to radiation fallout following the Chernobyl accident. Dr. Little, who came to DCEG from the United Kingdom, studied mathematics at Trinity College, University of Cambridge, and obtained his doctorate in mathematics at New College, University of Oxford.

Dr. Savage joined DCEG as a tenure-track investigator in 2006. In her research, she uses clinical, genetic, molecular, and epidemiologic approaches to understand telomere biology, its relationship to cancer, and the contribution of telomere length and variation in telomere biology genes to disease risk. Telomeres, the specialized nucleoprotein structures present at the ends of chromosomes, are essential for chromosomal stability. Telomeres shorten and eventually die as a natural consequence of aging; however, if cells bypass natural processes and continue to divide despite genomic instability, cancer can develop. Dr. Savage has conducted research into a telomere biology disorder called dyskeratosis congenita (DC), an inherited bone marrow failure syndrome that puts patients at high risk of bone marrow failure, leukemia, squamous cell cancers, pulmonary fibrosis, liver disease, and many other medical problems. Her work in DC led to the discovery of two novel causes of this syndrome: germline mutations in TINF2 and WRAP53.

As a pediatric hematologist/oncologist, Dr. Savage also conducts research into cancers and cancer predisposition syndromes that affect young people. Examples include osteosarcoma, a bone cancer for which she is leading the first international genome-wide association study (GWAS), and Li-Fraumeni syndrome (LFS), a rare, inherited disorder that leads to a higher risk of certain cancers. These cancers occur at younger ages in patients with LFS than in the general population. Dr. Savage initiated a new clinical and genetic study of LFS, and she also has led the development of an LFS international research consortium.

Before joining DCEG, Dr. Savage received her M.D. from the University of Vermont College of Medicine in Burlington, completed residency training in pediatrics at Children’s National Medical Center in Washington, D.C., and completed a fellowship in pediatric hematology/oncology with the NCI Center for Cancer Research Pediatric Oncology Branch and Johns Hopkins University in Baltimore, Maryland.

Dr. Yu joined DCEG in 2005 as a tenure-track investigator. His research addresses a wide variety of statistically and computationally challenging problems that have arisen in design and analysis of modern high-dimensional genetic and molecular epidemiologic studies. Dr. Yu has developed an adaptive design framework for replicating findings from previous genetic studies; methods for population stratification adjustment in GWAS; and improved statistical procedures for detecting susceptibility gene, gene-environment interaction, and pathway effects. He has been the primary statistician in several major studies, including GWAS of pancreatic and upper gastrointestinal cancers, as well as the Vitamin D Pooling Project of Rarer Cancers. In 2009, Dr. Yu received an NIH Merit Award for developing creative statistical methods for genetic epidemiologic studies.

Dr. Yu received a Ph.D. in biostatistics from the University of Pittsburgh in Pennsylvania and completed postdoctoral training in statistical genetics at Stanford University in Palo Alto, California. Before joining DCEG, he worked as a statistical geneticist at a biopharmaceutical company and as a research assistant professor of biostatistics at Washington University in St. Louis, Missouri.

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