On Monday, March 11, Margaret Kielian, Ph.D., will be presented the 13th annual Marshall S. Horwitz, M.D., Faculty Prize for Research Excellence in Robbins Auditorium at 4:00 p.m. The annual prize was established in memory of Marshall S. Horwitz, M.D., for his contributions to research and medical education at Einstein. Dr. Kielian, who is professor of cell biology and holds the Samuel H. Golding Chair in Microbiology, will present a lecture on her research titled “How Viruses Infect a Cell: Structure, Function, and Inhibition of Virus Membrane Fusion Proteins.” A reception will follow.
Margaret Kielian, Ph.D.Dr. Kielian studies enveloped viruses—viruses surrounded by lipid membranes containing viral proteins. They include the disease-causing, mosquito-borne alphaviruses such as Chikungunya virus and flaviviruses such as dengue, Zika, and West Nile. Together, these pathogens infect millions of people each year, and no vaccines or therapies exist to counter them. Dr. Kielian investigates how these enveloped viruses enter host cells, replicate, and then exit to infect other cells. Molecular studies of the entry and exit mechanisms required by these viruses can lead to targeted antiviral therapies and improved vaccine strategies.
Enveloped viruses infect cells by fusing their membranes with the membranes of host cells. Fusion is mediated by specialized membrane fusion proteins on the surface of the virus. Dr. Kielian and her lab have characterized the structurally related fusion proteins of alphaviruses and flaviviruses and the mechanism by which they mediate fusion. They developed methods to produce and purify the “postfusion” conformation of the alphavirus fusion protein and defined its structure in collaboration with the crystallographer Dr. Félix Rey of the Institut Pasteur. They then reconstituted the formation of this postfusion form on membranes in vitro and used this system to dissect the steps in the conformational change. Using the protein structure as a guide, they were able to generate critical domains of the fusion protein, thereby creating the first dominant-negative inhibitors of alphavirus and flavivirus fusion and infection. In addition to their importance to understanding virus entry, these studies have also provided important insights into structurally-related membrane fusion proteins of eukaryotic cells.
Dr. Kielian and colleagues recently discovered a new pathway by which alphavirus-infected cells transmit the virus to other cells during infection. Alphavirus infection drastically alters a host cell’s cytoskeleton—the proteins that support cells and help maintain their shape. The infected cell sends out long, thin extensions that make stable contacts with uninfected neighboring cells, enabling the virus to be efficiently transmitted from one cell to another. This mode of viral transmission may not only shield some copies of the virus from host antibodies but may also help to explain why symptoms of alphavirus infection can persist for so long.
Dr. Kielian has served on many NIH review panels including as a permanent member of the Experimental Virology study section. She has also served as a member of the Burroughs Wellcome Fund Pathogenesis of Infectious Disease Advisory Committee and as a reviewer for funding agencies including the Howard Hughes Medical Institute, the National Science Foundation, and the Human Frontier Science Program. She currently serves on the editorial boards of the Journal of Virology and Cell Host and Microbe, and is co-editor of the serial Advances in Virus Research.
Dr. Kielian’s honors include the Pew Scholar award, the American Cancer Society Junior Faculty Research award, the Hirschl/Weill-Caulier Career Scientist Award, and appointment as a fellow of the American Association for the Advancement of Science. She has organized major virology conferences and has lectured at seminars and symposia around the world. Dr. Kielian has been a mentor to numerous graduate and MSTP students, postdoctoral fellows, visiting scientists, and research technicians. She was the Director of the Cellular and Molecular Biology and Genetics Training Program for 12 years.
Dr. Kielian received her undergraduate degree in microbiology from the University of Nebraska and her Ph.D. degree in cell biology from The Rockefeller University working with Dr. Zanvil Cohn. She did her postdoctoral research in virology at the Yale University School of Medicine working with Dr. Ari Helenius. She then joined Einstein as an assistant professor of cell biology and is now a full professor with tenure and holds the Samuel H. Golding Chair in Microbiology.
Posted on: Wednesday, March 06, 2019