Colleagues: Recently Tenured

DAPHNE W. BELL, PH.D., NHGRI

Senior Investigator, Cancer Genetics and Comparative Genomics Branch, National Human Genome Research Institute

Education: Queen’s University, Belfast, Northern Ireland (B.S. in zoology and genetics; Ph.D. in biology and biochemistry)
Training: Postdoctoral training at Fox Chase Cancer Center (Philadelphia)
Before coming to NIH: Assistant professor of medicine, Harvard Medical School and Massachusetts General Hospital (Boston)
Came to NIH: In 2006
Selected professional activities: Member, Uterine Task Force of the NCI Gynecologic Cancer Steering Committee; associate editor-in-chief, Journal of Genomics
Outside interests: Enjoying the outdoors, swimming, photography, and art
Web site: https://irp.nih.gov/pi/daphne-bell

Research interests: My team studies uterine cancer, the seventh leading cause of cancer death among women in the United States, according to the American Cancer Society. Most uterine cancers arise from the inner lining of the uterus, or endometrium, and are called endometrial cancers.

Most human cancers, including endometrial cancers, are caused by the lifetime acquisition of genetic mutations known as driver mutations. During the past 20 years, it has become clear that the proteins made by some driver mutations can be turned off by cancer drugs that target the mutated protein. The tumor cells die while the normal cells remain unharmed. Therefore, detecting mutations that are present in human tumors, but absent in normal cells, is the first step toward identifying genetic targets that may be exploited clinically.

Although most endometrial cancers are associated with high cure rates, certain endometrial cancers—including the less-common serous endometrial cancers that typically arise in postmenopausal women—are clinically aggressive and associated with poor outcomes. My laboratory seeks to identify driver mutations that cause these aggressive cancers and, where appropriate, to determine their clinical relevance. We have found novel, high-frequency somatic mutations in phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3-kinase) in endometrial tumors; previously unrecognized cohorts of patients may benefit from therapies that target the PI3-kinase pathway.

Recently, we reported one of the first whole-exome sequencing studies of serous endometrial carcinomas: We discovered frequent mutations in genes that regulate chromatin remodeling and ubiquitin-mediated protein degradation, thus implicating these genes as likely drivers of serous endometrial cancer. In ongoing research we are assessing how mutations in these genes affect protein function, and we are expanding our search for additional genomic alterations that drive clinically aggressive endometrial tumors.

MICHELE K. EVANS, M.D., NIA

Senior Investigator, Laboratory of Epidemiology and Population Science; Deputy Scientific Director, NIA

Education: Barnard College of Columbia University, New York (A.B. in biology); Rutgers University, The Robert Wood Johnson Medical School, Piscataway, N.J. (M.D.)
Training: Residency in internal medicine at Emory University School of Medicine (Atlanta); fellowship training in medical oncology at NCI
Selected professional activities: Editorial Board, New England of Journal of Medicine; chair, External Advisory Board for the Lazarex-MGH Cancer Care Equity Program, Massachusetts General Hospital (Boston)
Outside interests: Girl Scout leader; Montgomery County Swim League referee and Stroke and Turn official; gardening
Web site: https://irp.nih.gov/pi/michele-evans

Research interests: I conduct interdisciplinary clinical and basic-science research that examines the underlying cause of health disparities—specifically the disproportionate incidence, morbidity, and mortality of age-related disease—among minority and low socioeconomic status (SES) Americans. My work dissects the interaction of race, SES, culture, behavior, environmental exposure, biologic vulnerabilities, genetics, social environment, health-care access, and quality of health care.

By pursuing related hypotheses at the bench and in the field, my work provides a two-way bridge between basic science and clinical epidemiological research. The ultimate goal of this approach is to transform scientific discoveries arising from laboratory, clinical, or population studies into clinical applications to reduce the incidence, morbidity, and mortality of age-associated diseases with particular interest in cancer and health disparities.

A major element of my work has been the development of the “Healthy Aging in Neighborhoods of Diversity across the Life Span Study” (HANDLS). HANDLS is a longitudinal, epidemiologic study of health disparities among socioeconomically diverse African-Americans and whites who reside in Baltimore. We designed HANDLS to disentangle the effects of race and SES on risk factors for morbidity and mortality; examine the incidence and progression of preclinical disease; and follow, over time, the development and persistence of health disparities, health status, and health risks. Data from this research are also used to investigate the mechanisms or biologic and molecular pathways that influence health and longevity trajectories of individuals.

The study, currently in its fourth longitudinal wave, examines the following domains: cognitive function, nutrition, neighborhood environment, anthropometry (human body measurements), renal function, cardiovascular health, physical performance, health services, molecular markers, genomic markers, and psychology. For more information about HANDLS, go to http://handls.nih.gov; to watch a video, go to https://www.youtube.com/user/NIAsHANDLS.

MARK GILBERT, M.D., NCI-CCR and NINDS

Senior Investigator and Chief, Neuro-Oncology Branch, National Cancer Institute-Center for Cancer Research and National Institute of Neurological Disorders and Stroke

Education: Johns Hopkins University, Baltimore (B.A. in human biology; M.D.)
Training: Residencies in internal medicine and neurology and fellowship training in neurology and neuro-oncology at Johns Hopkins
Before coming to NIH: Professor and deputy department chair, Department of Neuro-Oncology, Division of Cancer Medicine, University of Texas M.D. Anderson Cancer Center (Houston)
Came to NIH: In November 2014
Selected professional activities: Co-chair, Brain Tumor Committee, Radiation Therapy Oncology Group (Philadelphia); founder and leader of the Collaborative Ependymoma Research Network (CERN); founder and leader of the Brain Tumor Trials Collaborative (BTTC)
Outside interests: Hiking; rock climbing; mountaineering

Research interests: At M.D. Anderson, I developed and led large-scale, comprehensive, hypothesis-based clinical trials focused on finding treatments for malignant brain tumors. I led a clinical trial on the efficacy of the angiogenesis-inhibitor bevacizumab as a therapeutic for patients with newly diagnosed glioblastoma, the most common and lethal form of brain cancer. Although other studies had shown bevacizumab to have positive results in treating the disease, ours—the first randomized, double-blind study with the drug—demonstrated that it failed to increase overall survival or statistically significant progression-free survival. We established a new benchmark by successfully incorporating both real-time tumor analysis and patient-outcomes measures, including symptom burden, neurocognitive testing, and health-related quality of life.

At NIH, I am leading the Neuro-Oncology Branch, a collaboration between the National Cancer Institute (NCI) and National Institute of Neurological Disorders and Stroke (NINDS). We are working to develop new therapies for patients with primary brain and spinal-cord tumors. My vision is to build a highly collaborative, robust translational research program centered on finding treatments for central-nervous-system tumors; basic research observations will be rapidly translated into preclinical testing and then hypothesis-based clinical research trials, including important correlative studies.

Our areas of clinical research include exploring genetic changes in brain tumors to better understand how these cancers develop and become resistant to treatment; determining the impact of these tumors on the immune system by carrying out clinical trials designed to stimulate patients’ immune systems to help destroy the cancer; investigating the metabolism of cancer cells; and examining the impact of disease and treatment on cognitive function, symptoms, and quality of life.

In addition, we are using NCI’s and NINDS’s advanced-imaging technologies to develop new ways to image brain tumors so we can determine tumor activity, better define tumor location, and see whether therapeutic drugs are getting to—and working against—the cancers.

IVAN OVCHARENKO, PH.D., NLM-NCBI

Senior Investigator, Computational Biology Branch, National Center for Biotechnology Information, National Library of Medicine

Education: Novosibirsk State University, Novosibirsk, Russia (M.S. in physics; Ph.D. in physics and mathematics)
Training: Postdoctoral research at University of California at Berkeley (Berkeley, Calif.) and Lawrence Berkeley National Laboratory (Berkeley Hills, Calif.)
Before coming to NIH: Principal investigator, Lawrence Livermore National Laboratory (Livermore, Calif.)
Came to NIH: In 2007
Selected professional activities: Associate editor, Bioinformatics and BMC Bioinformatics
Outside interests: Hiking; skiing
Web site: https://irp.nih.gov/pi/ivan-ovcharenko

Research interests: My group’s current research focuses on deciphering the semantics and studying the evolution of the gene regulatory code in eukaryotes.

With less than two percent of the human genome having been sequenced, the search for noncoding functional DNA is an unsophisticated treasure hunt. We currently lack a fundamental understanding of the genomic language that governs the temporal and spatial dynamics of gene-expression regulation that is native to every living cell. In an effort to bridge the gap between genome sequencing and sequencing-data interpretation, we are developing pattern-recognition methods to functionally characterize noncoding DNA.

Understanding the gene regulatory landscape of the human genome will pave the way for studies of population variation in noncoding functional elements and promote the identification of disease-causing mutations residing outside of genes. Because mutations in gene-regulatory regions might be linked to an increased susceptibility to disease—not necessarily resulting in the disease itself—our research has a potential for mapping key regulatory elements in the vicinity of disease-associated genes. Computationally defined datasets of human regulatory elements tailored to specific common diseases (including heart disease, obesity, diabetes, and cancer) will facilitate the discovery of novel disease-susceptibility measurement methods that expressly target these elements.

To infer the function of noncoding genes, we use a variety of techniques—comparative genomics, Bayesian statistics, multiple sequence alignments, libraries of transcription-factor binding sites, microarray gene-expression data, sequence-pattern recognition techniques, dynamic programming, population genetics, and transgenic-animal experimentation (the latter through collaborations)—and the analysis of sequence data and evolutionary trends. Our research relies on collaborative studies with several research and clinical groups within the NIH and other research universities and institutions.

XIAOHONG (ROSE) YANG, PH.D., M.P.H., NCI-DCEG

Senior Investigator, Division of Cancer Epidemiology and Genetics, National Cancer Institute

Education: Beijing Normal University, Beijing (B.S. in biology; M.S. in cell biology); Lombardi Cancer Center, Georgetown University, Washington, D.C. (Ph.D. in physiology); Johns Hopkins Bloomberg School of Public Health, Baltimore (M.P.H. in epidemiology)
Training: NCI-DCEG
Came to NIH: In 2000 for training; became tenure-track investigator in 2006
Selected professional activities: Editorial board for Cancer Epidemiology, Biomarkers and Prevention; adjunct associate professor at the Chinese University of Hong Kong (Hong Kong)
Outside interests: Walking; playing tennis
Web site: https://irp.nih.gov/pi/rose-yang

Research interests: In my research, I combine statistical genetic analyses and cutting-edge genomic technologies to identify susceptibility genes for familial cancers including chordoma and cutaneous malignant melanoma/dysplastic nevi syndrome. I am also assessing the etiologic heterogeneity of breast cancer by integrating breast-cancer risk factors with genomic alterations in tumors.

My group spent more than 10 years searching for the genes implicated in familial chordoma, a rare type of bone tumor. In 2009, we identified the duplication of a specific gene as a major susceptibility factor for the cancer. To make this critical discovery, we used new technology—high-resolution array-based comparative genomic hybridization—that complemented our traditional gene-mapping strategy.

Recently, we used an exome-sequencing approach to identify a rare inherited mutation in a gene involved in maintaining telomere stability in melanoma-prone families, further supporting a role for abnormal telomeres in the development of melanoma. Finding genes in high-risk families may reveal important pathways involved in carcinogenesis in the general population.

In my investigation of the etiologic heterogeneity of breast cancer, I used tissue microarray to characterize the molecular signature of tumors and integrated tumor-profiling analyses to identify risk factors for specific cancer subtypes. I am leading breast-cancer studies in mainland China, Hong Kong, and Malaysia to identify distinct molecular alterations in tumors and adjacent normal tissues among Asian women and to examine the associations of these molecular changes with genetic and environmental risk factors, breast-tissue composition and density, and breast-cancer subtypes. Identifying unique exposure-subtype relationships in understudied populations will fill a critical knowledge gap concerning the observed racial heterogeneity of breast cancer and improve the risk stratification.