by Victoria A. Fisher, M.P.H.
In September 2014, Stephen J. Chanock, M.D., DCEG Director, announced the appointment of Shahinaz Gadalla, M.D., Ph.D., and Britton Trabert, Ph.D., M.S., 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. Gadalla investigates the role of genetic factors in cancer etiology and explores factors that may modify disease risk among individuals at high risk of developing cancer. She has received numerous awards for her work, including a DCEG Intramural Research Award and an NCI Director’s Intramural Innovation Award.
As a child growing up in Egypt, Dr. Gadalla’s goal was to become a physician in order to help people. However, once she started practicing medicine, she realized something was missing.
“It wasn’t enough for me to treat patients, to see them come and go,” she said. “I wanted to participate in producing what’s delivered to patients by exploring the science leading to better clinical care.”
Dr. Gadalla was offered a scholarship to attend the University of Maryland, Baltimore where she earned her master’s and Ph.D. degrees in epidemiology. After completing her doctoral research project under the mentorship of DCEG investigator James J. Goedert, M.D., she set her sights on the field of clinical epidemiology.
“I started my fellowship in DCEG with the desire to study outcomes after hematopoietic stem cell transplantation,” Dr. Gadalla said. “The moment I met with Sharon Savage, I realized that the Clinical Genetics Branch was a perfect match.”
As a fellow and later as a staff scientist, Dr. Gadalla focused on the role of telomere biology in outcomes after hematopoietic stem cell transplantation, starting with patients who received transplantation for dyskeratosis congenita, an inherited bone marrow failure and cancer susceptibility telomere biology disorder. She also utilized her training and interest in translational science to follow up on clinical observations from neurologists at the University of Rochester regarding cancer occurrence among their patients with myotonic dystrophy— a multi-system genetic disorder and the most common form of adult-onset muscular dystrophy.
Dr. Gadalla, Mark H. Greene, M.D., and other collaborators investigated patient cancer rates in the Swedish and Danish registry data and in 2011 reported elevated risks for a number of cancers, suggesting myotonic dystrophy as a new cancer susceptibility syndrome (Cancer risk among patients with myotonic muscular dystrophyJAMA, 2011).
“I got hooked on myotonic dystrophy research; it’s the questions that drive me,” Dr. Gadalla said. “We are now expanding, reaching out to find other large databases to re-confirm our observation. We are also pursuing new ideas to identify factors that predispose myotonic dystrophy patients to particular cancers.”
As a tenure-track investigator, Dr. Gadalla investigates the molecular and environmental drivers of myotonic dystrophy-associated carcinogenesis, and applies these insights into improving patient clinical care. “We are working closely with the myotonic dystrophy scientific and patient communities in the hope that we can together build more understanding,” she said.
In addition, Dr. Gadalla is continuing her research on telomere biology, leveraging lessons learned from dyskeratosis congenita to understand phenotypic variability in the wide spectrum of telomere biology disorders. She is leading studies to understand how telomere length may contribute to outcomes for patients who receive hematopoietic stem cell transplantation.
“I’m looking forward to building resources and expanding to new collaborators,” she said. “I’m a big believer in team science. It’s not an easy task, but when you work with rare diseases, it’s the way to go.”
Dr. Trabert concentrates her research on the role of exogenous and endogenous hormones in cancer etiology, and the relationship between chronic inflammation and risk of gynecologic cancers. She has received numerous awards for her work, including the NCI Director’s Intramural Innovation Award and NIH Fellows Award for Research Excellence.
Dr. Trabert first discovered the field of epidemiology during an undergraduate course on insects and health. “I thought the class and public health in general was fascinating, so my dad put me in touch with a family friend who studied birth defects at the Centers for Disease Control and Prevention (CDC),” she said. “That led me to pursue a master’s in epidemiology at Emory University, which was right next door to the CDC.”
While at Emory, Dr. Trabert became interested in sexually transmitted infections and associated morbidities. She went on to obtain another master’s degree in biostatistics from the University of Michigan, and ultimately a Ph.D. in epidemiology from the University of Washington.
Dr. Trabert was introduced to DCEG after presenting an abstract at the NIH National Graduate Student Research Conference. During that trip, she met Louise A. Brinton, Ph.D., M.P.H., Chief of the Hormonal and Reproductive Epidemiology Branch (HREB), Katherine A. McGlynn, Ph.D., M.P.H., Deputy Chief of HREB, and Nicolas Wentzensen, M.D., Ph.D., and realized that the Branch was a great fit for her career goals.
“I decided to pursue postdoctoral training with DCEG because I wanted to expand the breadth of my research in reproductive health to include cancer as an endpoint,” Dr. Trabert said.
As a fellow in HREB, Dr. Trabert evaluated the influence of pre- and post-natal risk factors on testicular cancer with Dr. McGlynn and expanded her research interests to include ovarian and endometrial cancers with Drs. Brinton and Wentzensen. Using the NIH-AARP Diet and Health Study, Dr. Trabert provided the strongest evidence to date that the use of estrogen plus progestin mitigates the increased risk of endometrial cancer observed with estrogen-only menopausal hormone therapy (MHT) (Is estrogen plus progestin menopausal hormone therapy safe with respect to endometrial cancer risk?Int J Cancer, 2013).
Dr. Trabert has been a key player in the development of two novel hormone assays with colleagues at the Frederick National Laboratory for Cancer Research. These assays measure androgens and androgen metabolites, and progesterone and progesterone metabolites.
“We know from research on MHT that progesterone reduces the risk of endometrial cancer, but increases the risk of breast cancer,” she said. “Combined with the existing capacity to measure estrogens and estrogen metabolites, these assays will help advance our understanding of the hormonal etiology of cancers in both men and women.”
In addition, Dr. Trabert is attempting to clarify how chronic inflammation is linked to ovarian and endometrial cancer risk. With Dr. Wentzensen and other colleagues, she recently published a study showing that women who take low dose daily aspirin, a non-steroidal anti-inflammatory drug, may reduce their risk of ovarian cancer (Aspirin, nonaspirin nonsteroidal anti-inflammatory drug, and acetaminophen use and risk of invasive epithelial ovarian cancer: a pooled analysis in the Ovarian Cancer Association Consortium.JNCI, 2014). They are currently working to replicate this significant finding in the Ovarian Cancer Cohort Consortium.
Dr. Trabert is also studying the long-term effects of fertility treatment, in particular whether ovulation-inducing drugs or specific in vitro fertilization procedures, which may result in ovarian trauma and inflammation, are associated with increased ovarian cancer risk. “This area of study is especially important, given the growing number of women seeking fertility treatment,” she said.
As Dr. Trabert continues in her career as a tenure-track investigator, she is motivated to better understand how reproductive health relates to cancer risk, and specifically risk for ovarian cancer. “I hope to find important etiologic clues that will inform ovarian cancer prevention, early detection, and treatment, all of which are critically needed for this disease,” she said.