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  • Center for International Health Research

  • Paul Knopf, PhD

    • Senior researcher for the Center for International Health Research
    • Stuart emeritus professor of medical science at Brown Medical School
      Brown profile

    Paul Knopf, PhD, received both a degree and a PhD in biophysics from MIT.

    Knopf was awarded a two-year National Institutes of Health (NIH)-sponsored postdoctoral fellowship appointment at the MRC Laboratory of Molecular Biology in Cambridge, England, in the research group of Francis Crick, PhD, (who was honored with the Nobel Prize in 1962).

    After his fellowship, Knopf spent eight years at the Salk Institute (TSI) for Biological Studies. While there, he worked as a postdoctoral fellow in the laboratory of Edwin Lennox, PhD, and was promoted to special research associate in charge of the membrane research group. At TSI he received support from NIH-NIAID (R01 grant and a prestigious Career Development Award).

    In 1972, he joined the faculty of Brown University as an associate professor of medical science in the division of biology and medicine. Knopf ascended the academic ladder, earning tenure in 1975 and full professorship in 1978. In 1992, he was named the first Charles A. and Helen B. Stuart Professor of Medical Science. He was the first chairman of the newly created department of molecular microbiology and immunology in 1994 and served until 1997. In 1998, Knopf was honored as Teacher of the Year for his teaching of undergraduate courses in immunology.

    Knopf's research awards include an Alexander von Humboldt Foundation travel grant to conduct research at Max-Planck-Institute fur Molekular Genetik, a Fulbright Fellowship to conduct research in Melbourne and a Fogarty Fellowship for research in London and Rome.

    He maintained continuous grant support from 1966 to 2001 for his research, from NIH-National Institute of Allergy and Infectious Disease, Rockefeller Foundation, E. M. Clark Foundation, World Health Organization, NIH-NS, Multiple Sclerosis Society, American Cancer Society, and The Brain Tumor Society; plus local grants from the Rhode Island Foundation and Brown University (Solomon Award).

    Knopf has conducted basic science research in protein biosynthesis (hemoglobin and immunoglobulin, IgG); surface expression and secretion of IgG; development of humoral immunity to infection by the parasitic worm, Schistosoma mansoni; blocks in schistosome development in nonpermissive hosts and immune privilege in the brain; behavioral changes induced in rats by micro-infusion of antibodies to brain cell proteins. The following are examples of his major contributions:

    • Co-discovery (and naming) of polyribosomes as the functional unit in hemoglobin synthesis in rabbit reticulocytes
    • Development and first reporting of the reticulocyte lysate cell-free protein synthesizing system plus using exogenous mRNA as the template
    • Contributing to the understanding of IgG biosynthesis by demonstrating that the variable and constant region segments of the molecule are not synthesized on separate templates despite being encoded in separate genetic loci on the same chromosome, requiring a process for uniting the genetic information; and delineating the intracellular process leading to secretion and surface localization of IgG
    • Demonstrating that an excess of schistosomula (migrating larval schistosomes) are trapped in the lungs of previously infected rats, and not the skin (as proposed in the then existing reinfection paradigm of immunity), by using a passive immunization protocol on different days post reinfection, later confirmed by a radiolabelled worm migration assay
    • Identification of candidate vaccine antigens and cloning of a schistosome gene by differential screening using antisera from resistant and nonresistant rat strains of the same species
    • Demonstrating that protein antigens introduced into the rat brain lateral ventricle (by micro-infusion via an indwelling cannula after healing of the BBB (blood-brain barrier)) induce a strong humoral immune response, mainly through stimulation of cervical lymph nodes that received antigen exiting the brain by existing fluid drainage along channels leading to cranial nerves

    These and related studies on survival or rejection of a brain tumor allograph redefined immune privilege as induction of a Th2 response-dominance that muted/suppressed Th1-induced cell-mediated (CTL) anti-tumor responses; similar immunosuppressive responses were demonstrated using the rat EAE model and and then exposing such immunized rats to a standard EAE challenge, demonstrating that micro-infusion of antibodies behind an intact BBB cross-reactive with brain cell antigens can lead to behavioral changes on locomotive activity.