Colleagues: Recently Tenured
NIHAL ALTAN-BONNET PH.D., NHLBI
Senior Investigator and Head, Laboratory of Host-Pathogen Dynamics, National Heart, Lung, and Blood Institute
Education: Hunter College, City University of New York, New York (B.A. in biology and chemistry); The Rockefeller University, New York (Ph.D. in cellular biophysics)
Training: Postdoctoral research fellow, NICHD’s Cell Biology and Metabolism Branch
Before coming to NIH: Assistant Professor, Federated Department of Biological Sciences, Rutgers University (Newark, N.J.)
Came to NIH: In 1999–2005 for training; returned in 2013 as a Stadtman investigator in NHLBI
Selected professional activities: Serving on NIH and NSF study sections; mentoring K–12 and college students; serving as reviewer for scientific journals and on editorial boards
Outside interests: Taking road trips with family (for example, to national parks); discovering roadside diners; hiking; swimming; reading
Research interests: By combining cutting-edge imaging technologies with lipidomic and proteomic approaches, my lab has discovered novel replication and transmission mechanisms that are surprisingly shared by many different human, animal, and plant viruses. Focusing on shared attributes among viruses has led to a deeper understanding of what it means to be a virus. Our investigations have revealed that although there are many significant differences among viruses—in genomes, capsid structures, and replication mechanisms—surprisingly there are also many common critical features of their lifecycles that enhance their infectivity. For example, we have found that many viruses exploit certain lipid-enriched membranes, such as phosphatidylinositol-4-phosphate and cholesterol, to dock and assemble their enzymes, which in turn we have shown leads to greater efficiency in replicating their genomes. More recently we have discovered that many different viruses transport themselves to the next host as populations inside vesicles, rather than as individuals. We showed that this ability enhances their genetic diversity and transmission efficiency. Discovering these and other common viral attributes we believe will not only provide insight into the virus-host interface but will also provide opportunities for novel types of panviral therapeutic interventions.
SONJA M. BEST, PH.D., NIAID
Senior Investigator and Chief, Innate Immunity and Pathogenesis Section, Laboratory of Virology, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases
Education: University of Adelaide, Adelaide, SA, Australia (B.S. with majors in immunology and microbiology, second major in zoology); Australian National University, Canberra, Australia (Ph.D. in biochemistry and molecular biology)
Training: IRTA visiting fellow and later a research fellow in NIAID’s Laboratory of Persistent Viral Diseases
Came to NIH: In 1999 for training; in 2007 became a staff scientist; in 2009 became a tenure-track investigator
Selected professional activities: Editorial board member, Journal of Biological Chemistry, Journal of Virology, and Journal of Interferon and Cytokine Research; board of reviewing editors, Science Translational Medicine; invented monoclonal antibody specific for the extracellular domain of human protein interferon-alpha and -beta receptor subunit 1
Outside interests: Hiking with the dog; entertaining friends; pencil drawing and sketching; traveling
Research interests: The world has witnessed several major emerging viral diseases in the past 20 years, including West Nile virus, Zika virus, and Ebola virus. I am interested in understanding the mechanisms underpinning early immune activation after infection with RNA viruses and how emerging viruses evade these early responses to cause disease. The innate immune response is rapidly engaged after virus infection and functions to limit virus replication and mobilize adaptive immune responses, in large part through the production of type I interferons (IFN). The molecular interactions between this critical IFN response and the infecting virus (specifically, the ability of the virus to antagonize the response) can determine host tropism and the potential of a virus to emerge from an animal source into humans. These viral evasion strategies are not always functional in mice and can be a significant limitation in developing animal models of disease for testing of vaccines and other countermeasures.
We are using the insight from these virus-host interactions to develop better mouse models of disease by engineering mice with targeted gene deletions or gene knock-ins in key molecules involved in innate signaling and virus restriction. Our current virus models include emerging flaviviruses (such as Zika virus and tick-borne encephalitis virus) and filoviruses (Ebola virus). Specific topics currently being explored in the laboratory include the mechanisms used by these viruses to modulate host innate immunity, the role of novel IFN-stimulated genes in host-specific resistance to virus infection, and the importance of macrophage and dendritic-cell function to antiviral innate and adaptive immune responses. Understanding key events at this virus-host interface will help us to understand virus emergence, and engineering better mouse models will facilitate design of vaccines and therapeutics.
MELISSA C. FRIESEN, PH.D., NCI-DCEG
Senior Investigator, Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute
Education: University of British Columbia, Vancouver, B.C., Canada (B.Sc. in chemistry); School of Occupational and Environmental Health, University of British Columbia, Vancouver (M.Sc. and Ph.D.)
Training: Research fellow, Population Health Learning Observatory (Vancouver); research fellow, Centre for Occupational and Environmental Health, Monash University (Melbourne, Australia); postdoctoral research fellow, Environmental Health Sciences, University of California at Berkeley, (Berkeley, Calif.)
Came to NIH: In 2009
Selected professional activities: Member of editorial review board of the Journal of Occupational and Environmental Hygiene; member of the international advisory board of the Annals of Occupational Hygiene
Outside interests: Traveling; bicycling
Research interests: I am developing quantitative-assessment strategies and tools to accurately calculate lifetime occupational exposures to various substances among men and women. These exposure estimates are used to identify causes of increased cancer risk. By using more-refined and more-proximal exposure measures, I have identified and quantified exposure-response relationships for several exposure-disease associations that have not previously been published: straight metalworking fluid and bladder cancer; lead and meningioma; pentachlorophenol (organochlorine compound used as a pesticide and a disinfectant) and non-Hodgkin lymphoma; and wood dust and hospitalization for chronic lung diseases.
To improve the transparency and efficiency of exposure-assessment efforts in case-control studies of cancer, I developed a framework to apply exposure decision rules that link occupational information from study subjects to estimates of occupational exposure. I used this approach to evaluate occupational exposure to metalworking fluids and the risk of bladder cancer. I demonstrated for the first time that quantitative estimates from population-based studies are comparable to the high-quality assessment efforts in industry-based studies. Both methods yield similar and consistent exposure-response associations.
I have extended the use of statistical models—to predict historical exposure—commonly used in industry-based studies to population-based studies. For example, I have developed a framework to combine subjective ratings of exposure from job-exposure matrices and exposure measurements to better discriminate between time and job differences in exposure levels in population-based studies. I have also extended the use of meta-regression models to determinants of exposure concentrations from occupational and environmental exposure scenarios reported in the published literature.
I have also created exposure-assessment tools by efficiently transforming participants’ verbatim responses in occupational questionnaires into usable data. I led the development of an algorithm to automatically code job descriptions into standardized occupation classification codes (https://soccer.nci.nih.gov). I also generated keyword-based approaches to use the verbatim responses to systematically extract variables representing exposure scenarios that can be used in decision rules and to assign more-detailed questionnaires to subsets of study participants.
I have found that the accuracy of exposure-assessment tools may differ by sex. By pooling occupational responses from three studies, I found gender differences in the prevalence and frequency of work tasks. In addition, there are several factors that may explain why women’s physiologic responses to exposure may be different from men’s including hormonal influences and physiologic differences that can influence internal exposure dose. Failure to at least consider gender differences may result in biased estimates of risk.
GRETCHEN L. GIERACH, M.P.H., PH.D., NCI-DCEG
Senior Investigator, Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute
Education: Pennsylvania State University, University Park, Pa. (B.S. in behavioral health); University of Pittsburgh Graduate School of Public Health, Pittsburgh (M.P.H. and Ph.D. in epidemiology)
Training: Cancer Prevention Fellow, Cancer Prevention Fellowship Program, Office of Preventive Oncology, NCI
Came to NIH: In 2006 for training; in 2010 appointed as a tenure-track investigator
Selected professional activities: Chair of NCI-DCEG’s Breast Cancer Working Group; co-chair of NCI-DCEG’s Hormone Laboratory Advisory Committee
Outside interests: Enjoys spending time with her husband, two sons, and yellow Labrador retriever; cooking; traveling
Research interests: I conduct integrative molecular epidemiologic research aimed at advancing our understanding of breast-cancer etiology and progression. My research program focuses on breast density and hormones, two of the strongest risk factors for sporadic breast cancer among women.
My work on breast density uses a range of technologies and approaches to improve the measurement of density, delineate risk factors for elevated density, and understand mechanisms that mediate its relationship to breast-cancer risk and progression. I lead the BREAST Stamp Project [https://dcegpreview.cancer.gov/research/cancer-types/breast-cancer/radiology-evaluation-study-tissues-stamp-project], which aims to characterize the radiologic, histologic, and molecular features of dense breast tissue and to understand how the microenvironment of dense breasts promotes neoplastic transformation of the breast epithelium. I am also investigating whether standardized microscopic (terminal duct lobular involution) and macroscopic (mammographic breast density) measures of breast-tissue architecture could represent clinically useful intermediate endpoints of risk in a nested case-control study of 1,000 women diagnosed with benign breast disease, among whom 500 subsequently developed breast cancer. Findings from these efforts could improve risk-assessment strategies for the increasing number of women undergoing breast biopsies after a mammogram.
In light of growing evidence indicating that reductions in mammographic density, specifically among tamoxifen users, may predict reduced risk of breast-cancer development and progression, my colleagues and I are integrating serial measures of mammographic breast density into a cohort study of patients with invasive breast cancer diagnosed within a general community health-care plan. In the Ultrasound Study of Tamoxifen [https://dceg.cancer.gov/research/cancer-types/breast-cancer/ultrasound-study-tamoxifen], we are using novel 3-D whole-breast ultrasound-tomography methods to assess changes in breast sound speed, a surrogate for volumetric breast density, within the first year of clinically indicated tamoxifen use. These studies may provide support for future investigations evaluating change in mammographic density as a “biosensor” of factors that increase or decrease breast-cancer risk.
To study hormonal carcinogenesis, I conduct epidemiologic studies to evaluate the influence of endogenous and exogenous hormones on both radiologic and histologic measures of breast-tissue composition and risk. The ultimate goal of my research is to facilitate the development of improved strategies for risk stratification, prevention, early detection, and treatment by better understanding breast carcinogenesis and the basic mechanisms underlying established risk factors.
HONG XU, PH.D., NHLBI
Senior Investigator, Laboratory of Molecular Genetics, National Heart, Lung, and Blood Institute
Education: Nankai University, Tianjin, China (B.S. in biology]; Peking University, Beijing, China (M.S. in molecular biology); Johns Hopkins University School of Medicine, Baltimore (Ph.D. in genetics]
Training: Postdoctoral fellow, Department of Biochemistry and Biophysics, University of California, San Francisco (San Francisco); Research area was genetics and developmental biology
Came to NIH: In 2010
Outside interests: Hiking; working in the yard
Research interests: My research focuses on several of the most important but unresolved issues related to our second genome—our mitochondrial DNA (mtDNA)—which is transmitted through the maternal lineage. Mutations in mtDNA are associated with many inherited and age-related disorders including neurodegeneration, muscular atrophy, and diabetes. My colleagues and I want to understand how a mother can provide healthy mitochondria, without harmful mtDNA mutations, to her children.
I previously developed a genetic approach to select for inheritable mtDNA mutations in fruit flies of the genus Drosophila, which paved the way for studying mtDNA genetics and modeling human mtDNA diseases. My lab reported that the ectopic expression of an alternative repository enzyme can fully rescue a lethal mtDNA mutation, suggesting a potential therapy for currently incurable mtDNA diseases.
We also discovered that the selective proliferation of healthy mitochondria containing wild-type mtDNA would increase the proportion of the wild-type genome in oocytes. The greater number of healthy mitochondria would outcompete the unhealthy mitochondria and consequently limit the transmission of deleterious mtDNA variants to the next generation. Our model of selective inheritance explains the strong purifying selection observed in animal studies and challenges the existing dogma known as bottleneck inheritance as an effective way to weed out the mtDNA mutations.
We also revealed a translational boost on the mitochondrial outer membrane that promotes the synthesis of nuclear-encoded mitochondrial proteins. This boost supports the prodigious mtDNA replication during oogenesis and explains how a single nuclear genome within a germ cell can support the biogenesis of millions of mitochondria to power the early embryonic development. We are now combining our new techniques in mtDNA genetics with powerful manipulations of the nuclear genome in Drosophila to investigate the cellular processes that regulate mitochondrial genome organization, segregation, and expression. We are exploring how these regulations affect mtDNA inheritance. We are also undertaking a high-risk endeavor to develop new methods for mtDNA transformation. This process would help to generate cell and animal models of human mtDNA diseases and facilitate the development of effective therapies.
This page was last updated on Friday, April 8, 2022