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DCEG Gains Two New Earl Stadtman Investigators

by Victoria A. Fisher, M.P.H.

Lisa Mirabello, Ph.D., M.S., and Steven C. Moore, Ph.D., M.P.H., have been selected as NIH Earl Stadtman Investigators. Named after a noted biochemist at the National Heart, Lung, and Blood Institute, the Stadtman program is a trans-NIH recruitment initiative designed to attract the most talented early career scientists to NIH.

Dr. Mirabello joined DCEG in 2007 as a postdoctoral fellow in the Clinical Genetics Branch (CGB) and became a research fellow in 2010. Dr. Mirabello is interested in understanding the contribution of genomic and epigenomic alterations to cancer etiology. She has received a number of awards for her work in this area, including a DCEG Fellowship Achievement Award as well as DCEG and NIH Fellowship Awards for Research Excellence.

Dr. Mirabello’s childhood dream was to become a veterinarian, but her priorities changed once she worked in an animal clinic after studying animal science at Cornell University. “I became more interested in understanding why the animals were sick, what caused the underlying disease,” she said. “That’s what steered me to get a master’s in experimental pathology and ultimately a Ph.D. in infectious disease and population genetics.”

During her doctoral work at the State University of New York in Albany, School of Public Health, Dr. Mirabello studied mosquito population genetics to understand the epidemiology of malaria in humans. “That work inspired my interest in public health,” she said. “It eventually led me to think about cancer epidemiology and ways that I could apply my unique background in population genetics to understand why people get cancer. That’s when I met Dr. Savage and realized that DCEG was a perfect fit.”

As a tenure-track investigator in the Genetic Epidemiology Branch, Dr. Mirabello is focused on three major areas of study: osteosarcoma, Diamond-Blackfan anemia (DBA), and human papillomavirus (HPV) methylation and genomics.

Dr. Mirabello, Sharon A. Savage, M.D., Chief of CGB, and colleagues are using genome-wide association studies and exome sequencing to better understand the genetic etiology of osteosarcoma, a rare bone cancer. In addition, Dr. Mirabello is examining how genetic variation affects patient outcomes, such as metastasis, survival, and response to chemotherapy. “The end goal is to find something that could be a novel marker of disease or clinical outcome,” she explained.

Dr. Mirabello became interested in DBA, a cancer predisposition syndrome, through her work on osteosarcoma. DBA patients have a high incidence of osteosarcoma, and she has been leading the hunt for new disease-causing mutations.

In addition, Dr. Mirabello is collaborating with Mark Schiffman, M.D., M.P.H., Nicolas Wentzensen, M.D., Ph.D., M.S., and colleagues on HPV methylation and genomics. This research is aimed at understanding the unique, highly carcinogenic nature of HPV type 16 and identifying markers to distinguish the common benign from the rare carcinogenic infections. They have initiated new projects to study the genome-wide genetic variation and methylation of the carcinogenic HPV types, starting with HPV 16.

“We are currently working on the largest study to compare all the carcinogenic HPV types, and variants within types, to try to pin down which genetic variants are linked to carcinogenicity,” she said.

Dr. Moore, also selected as an NIH Earl Stadtman Investigator, joined the Nutritional Epidemiology Branch (NEB) in 2005 through the Yale-NCI Cooperative Graduate Training Program in Cancer Epidemiology and became a research fellow in 2009. His research focuses on the role of physical activity and obesity in the development of cancer. Dr. Moore has received a number of awards for his work in this area, including a DCEG Fellowship Achievement Award and the Karen Hornbostel Memorial Award from the American College of Sports Medicine.

An avid runner since the age of 15, Dr. Moore credits this health-oriented passion and his experience working at the AIDS Division in the Connecticut Department of Public Health for inspiring his initial interest in public health. “There was a community health side to that job, but there was also a focus on data that I found very intriguing,” he said.

Dr. Moore went on to receive his M.P.H. and Ph.D. in cancer epidemiology from the Yale School of Public Health, where he discovered the emerging field of energy balance. He also developed an early interest in studying the molecular and mechanistic mediators of cancer.

As a tenure-track investigator in NEB, Dr. Moore studies the role of obesity-related factors on cancer risk, including waist circumference, sedentary behavior, and physical activity. With Charles E. Matthews, Ph.D., and other collaborators, he is exploring these questions in large population-based studies.

“Right now, we’re working on the largest study to date of physical activity and cancer using pooled data from the NCI Cohort Consortium,” he said. “This study is unique in that it’s the first Cohort Consortium study to examine a single exposure across all individual cancer types. By providing definitive data on physical activity and cancer risk, this study could help to inform or refine public health guidelines for physical activity.”

Dr. Moore is also a pioneer in the field of metabolomics, which applies novel high-throughput technology to analyze small-molecule metabolites in biospecimens like blood or urine as a way to understand how molecular pathways may influence cancer risk. In studying the metabolomics of energy balance, Dr. Moore, Joshua Sampson, Ph.D., Rashmi Sinha, Ph.D., Deputy Chief of NEB, and colleagues have been instrumental in uncovering biomarkers for body mass index and diet.

“As a group, we were some of the very first people to examine how metabolomics can help predict future cancer,” Dr. Moore said. “It’s been exciting to see this collaboration come together.”

As DCEG investigators, Drs. Mirabello and Moore enjoy the independence and intellectual freedom of academic research. Their motivation stems from a passion for discovery and a desire to make a lasting impact on the field of public health.

“I hope that one day my discoveries may be translated into tools to improve cancer screening or management, and ultimately improve human health,” Dr. Mirabello said. “That is my goal.”

“The most exciting thing for me is finding something new,” Dr. Moore said, “finding something that nobody has ever seen before. And sometimes making observations that in one light are not striking but in another light—when you think about them again—are a big deal.”

Back to the Spring 2014 issue of Linkage