Member SpotlightsRNAi Applications in Lung Developmental Biology Heber Nielsen, M.D. A Science Advisory Board Member Since 2001 Heber Nielsen, M.D. is a Professor of Pediatrics, Tufts Medical Center and Tufts University School of Medicine, US. Nielsen received his undergraduate degree from Whitman College in 1971 (Physics major), and his M.D. from the University of Utah School of Medicine in 1975, with membership in the Senior Honors in Pediatrics program. He later obtained a research fellowship in the Division of Neonatology at the University of Utah School of Medicine (1975-1976), a pediatric residency at the Massachusetts General Hospital (1976-1978), and completed his fellowship in Neonatal/Perinatal Medicine with the Joint Program in Neonatology at the Brigham and Woman’s Hospital in Boston (1978-1981). While an Assistant Professor of Pediatrics and of Ob/Gyn at the University of Texas Southwestern Medical School (1981-1986), Nielsen developed his independent research program in lung developmental cell biology. He returned to Boston in 1986 as an Associate Professor of Pediatrics,Tufts Medical Center and Tufts University School of Medicine (Division of Newborn Medicine). (He was later promoted to Professor of Pediatrics). This year he became a member of the Cell and Molecular Developmental Biology Graduate Studies Program at the Tufts Sackler School of Graduate Education. In addition to this teaching responsibilities, Nielsen has served as a mentor to aspiring physicians and graduate students. Nielsen is a member of the American Pediatric Society, Society for Pediatric Research, Perinatal Research Society, American Thoracic Society, and the American Society for Cell Biology. He has received the “Best Research Abstract Award” from the American Academy of Pediatrics and from the Massachusetts Thoracic Society, and has been listed in the Best Physicians directory. He currently serves on the Council of the Eastern Society for Pediatric Research and the New England Perinatal Society. Nielsen has been a permanent member on two National Institutes of Health (NIH) study sections and has been an invited grant reviewer for the Wellcome Foundation (Great Britain) and the Science Foundation Ireland, in addition to numerous visiting professor invitations to organizations in the US, Mexico, Canada, and Germany. In this Member Spotlight, Nielsen discusses RNAi applications with The Science Advisory Board. Describe your current research interests. I am the senior investigator in the Lung Developmental Cell Biology laboratories at Tufts Medical Center. I have long-standing funding from the NIH as well as several foundations. My current research focuses on the mechanisms of ErbB receptor regulation of late gestation fetal lung development, with particular emphasis on the Epidermal Growth Factor receptor and on the ErbB4 receptor. I grew up with the desire to have a career in scientific research. During college this goal became focused on biomedical studies, and during medical school I developed a passion for caring for and studying babies, especially those born prematurely. Because the major cause of illness in premature babies is lung disease (based on lung immaturity at premature birth) it seemed natural to focus on the cell biology of lung development. Has your career developed as expected? Originally I expected my career to develop along the lines of organ physiology, instead of cell and molecular biology. But I quickly learned during training that the questions and problems which I found most interesting and intriguing were cell biology and molecular biology-based. My current career path very rapidly developed early in my fellowship training. I continue to be fascinated with the questions on how cell fate and differentiation are regulated at the molecular level in the developing lung. I hope to be able to mark out clear biological signaling pathways that control alveolar differentiation in the developing lung. I believe that such knowledge will have a major impact on developing new therapeutic strategies to treat lung diseases caused by premature birth. Describe how RNAi methods are applicable to your research, and what particular pieces of equipment are utilized? One problem of our research is that ErbB receptor knockout animals show embryonic lethality before the progression of lung development, so alternative methods of evaluating specific functions of the ErbB receptors in lung development are needed. siRNA technology provides an important tool for studying specific functions of ErbB receptors. We have also found siRNA technology to be highly useful in studying the importance of other regulatory genes in the process of lung morphogenesis. We are now beginning projects to identify the developmental function of microRNA’s in lung development. The biology of siRNA action is based on the mechanisms through which microRNA regulates gene function, so the use of siRNA as a tool and the study of microRNA function represent cooperative areas of study. What type of cell culture or organism is used? What are your target genes? We mostly use primary cultures of fetal lung type II alveolar epithelial cells and fetal lung fibroblasts. There are few cell lines appropriate for type II cell studies, and none of these are fetal cells, so we rarely use cell lines. Primary fetal lung cell cultures have proven to be robust in maintaining their developmental phenotype over several days in culture. Much of our current work targets the ErbB4 receptor. We are also beginning work to target proteins that process the ErbB4 receptor, including the tumor necrosis factor alpha conversion enzyme and gamma secretase. In a separate area of study we are targeting extra cellular matrix proteins such as tenascin. For this work we use cultures of whole embryonic lung. Although RNAi is a relatively new technology, the field quickly became dominated by Intellectual Property (IP) rights. Please comment on this process, and at what stage does your role at Tufts Medical Center and Tufts University School of Medicine contribute to the establishment of IP? IP rights have so far not played a large role in our studies, as we do not as yet envision RNAi as a potential therapeutic tool. I believe that the largest impact will be seen if the use of RNAi technology allows us to identify important pathways to target for therapy in premature infants. What segment of biotechnology do you believe has been affected the most by RNAi? I believe that the emerging use of RNAi as a tool for drug target discovery has been most affected. What future therapeutic areas will receive the greatest impact of RNAi? I feel that the cancer therapy field will receive the greatest impact of RNAi. This belief is based on the significant prevalence of cancer and its impact on health. To discuss RNAi and other topics with fellow Science Advisory Board members, please visit our community forum. Weblinks Heber Nielsen, M.D. Faculty Page at Tufts Sackler School of Graduate Biomedical Sciences Publications Chetty A, Manzo N, Waxman A, Nielsen HC. Modulation of insulin-like growth factor binding protein -2 and -3 in hyperoxic injury in developing rat lung. Pediatric Research 2005; 58:222-228. Chetty A, Cao G-J, Nielsen HC. Insulin-like growth factor-1 signalling mechanisms, type I collagen and alpha smooth muscle actin in human fetal lung fibroblasts. Pediatric Research 2006; 60:389-394. Dammann CEL, Nassimi N, Liu W, Nielsen HC. Dexamethasone interacts with ErbB signaling in fetal mouse lung surfactant synthesis. European Respiratory Journal 2006; 28:1117-1123. Zscheppang K, Korenbaum E, Bueter W, Ramadurai S, Nielsen HC, Dammann CEL. ErbB4 receptor dimerization, localization and co-localization in mouse lung type II epithelial cells. Pediatric Pulmonology 2006; 41:1204-1212. Volpe MV, Rallabandi S, Pham LD, Nielsen HC. Hoxb-5 down regulation alters Tenascin-C and FGF10 expression patterns in pseudoglandular period fetal mouse lung. Frontiers in Bioscience 2007; 12:860-873. Villanueva D, Wang K, Nielsen HC, Ramadurai SM. Expression and activation of specific protein kinase C isoforms during development of fibroblast-type II cell communication. Experimental Lung Research 2007; 33:185-196. Liu W, Zscheppang K, Murray S, Nielsen HC, Dammann CEL. The ErbB4 receptor in fetal rat lung fibroblasts and type II cells. Biochimica et Biophysica Acta 2007; 1772:737-747. Zscheppang K, Liu W, Volpe MV, Nielsen HC, Dammann CEL. ErbB4 regulates fetal surfactant phospholipid synthesis in primary fetal rat type II cells. Am J Physiol (Lung Cell Mol Physiol) 2007; 293:429-435. ### << Previous [ View All Member Spotlights ] |
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