This project brings together five groups, at Boston Children’sHospital (Harrison), The Ragon Institute of MGH, MIT and Harvard (Schmidt), The Duke Vaccine Institute (DHVI) (Moody, Sempowski), the Duke University School of Medicine Department of Immunology (Kelsoe, Kuraoka), and Boston University (Kepler). We also have an on-going collaboration with Georgiou and co-workers at the University of Texas, Austin), to capitalize on their powerful technology for analyzing the human serum antibody repertoire; they will continue to collaborate as part of this renewal.
PI of the P01 and PI of Project 3 and Core A.
Dr. Harrison is Giovanni Armenise-Harvard Professor of Basic Biomedical Sciences at Harvard Medical School and Children's Hospital, Boston, and Investigator in the Howard Hughes Medical Institute. He is also Head of the Laboratory of Molecular Medicine at Children's Hospital. He is a leading expert on the structure of viruses and viral proteins, as studied at high resolution by x-ray crystallography and (recently) by cryoEM. He has worked on the surface glycoproteins of flaviviruses, herpesviruses, coronaviruses, and HIV/SIV, as well as on influenza-virus, HA mediated fusion mechanisms. He has led this project during the past five years.
M. ANTHONY MOODY
PI of Project 1
Dr. Moody is Associate Professor of Pediatrics at Duke and has been an active member of the current P01, taking on the role of Project 1 lead during the final year of the grant. Dr. Moody is an expert in the use of flow cytometry for sorting and analysis of cells. He developed the flow cytometric strategies described in this P01 application and continues to develop novel strategies for the isolation of B cells by FACS. He has a background in chemistry and prior work experience in the development of peptide-based vaccines, the creation of novel antigen-specific reagents, production of adjuvants for experimental vaccines, and the analysis of vaccination and infection by monoclonal antibody isolation. His laboratory uses these techniques to study various infectious diseases including HIV-1, syphilis, and influenza.
Dr. Moody is also an experienced clinician in Pediatric Infectious Diseases and he serves as the Chief Medical Officer of DHVI and the Director of the DHVI Repository.
PI of Project 2
Dr. Kelsoe is the James B. Duke Professor of Immunology at Duke University, and a member of the Duke Human Vaccine Institute. He is an expert in the biology and somatic genetics of B lymphocytes and pioneered our current understanding of B-cell hypermutation and affinity-driven selection in germinal centers. He has long standing collaborations with B.F. Haynes to study the role of immunological tolerance in the prevention of robust humoral immunity to HIV-1 and with T.B. Kepler in modeling the population structure and dynamics of B-cell responses. Recent work with T. Nojima, A.G. Schmidt, and S.C. Harrison have focused on the population genetics of humoral responses to influenza HA. The novel cloning methods developed in Kelsoe’s laboratory will be used to illuminate the phenomenon of clonal imprinting characteristic of serial influenza exposures
co-Investigator of Project 2
Dr. Kuraoka is a senior research scientist with an appointment in the Department of Immunology at Duke University. Following his doctoral training at the University of Tokyo, Dr. Kuraoka held postdoctoral positions with two highly regarded experts in B-cell biology, T. Takemori and Y. Takahashi. Subsequently, Kuraoka joined G. Kelsoe’s laboratory at Duke and was instrumental in developing the Nojima culture method for single B-cell cloning and in understanding the role of Aicda expression in B-cell development. He has provided leadership in the extension of the Nojima culture methods to B cells from humans and non-human primates.
AARON G. SCHMIDT
co-PI of Project 3
Dr. Schmidt is an Assistant Professor in the Department of Microbiology at Harvard Medical School, Boston and a Group Leader at the Ragon Institute of MGH, MIT and Harvard, Cambridge. His Ph.D. in Virology at Harvard concerned inhibitors of dengue virus fusion. His postdoctoral work led to several key papers on this project of which he is author, and his leadership and supervisory skills have helped in coordinating the work on Project 3 with that of various collaborators and with the other projects. His expertise extends from biochemistry and structural biology to viral immunology and contemporary methods in protein directed evolution and protein engineering.
A link to The Schmidt Laboratory