Faculty Profile: Paul M. Knopf, PhD

Paul M. Knopf
Paul M. Knopf, PhD
Charles A. and Helen B. Stuart Professor Emeritus of Medical Science
Molecular Microbiology & Immunology
Work: +1 401-863-1607
Prof. Knopf's career interest has been in protein biosynthesis, initially in general but primarily in immunoglobulins and their role as antibodies in humoral immune reponses. Since joining the Brown faculty, he has studied protective antibody responses to worm and protozoan parasitic infections (vaccine development against schistosomiasis and malaria), responses to antigens in the brain (autoimmunity), and most recently the role of complement C3d in the induction of the T-dependent antibody response.

Biography

As an immunologist, I am intrigued by how the immune system responds to challenges. I first took an interest in biology as an undergraduate majoring in physics at MIT. After going on to receive a doctorate in biophysics from MIT, I completed post-doctoral training at the Medical Research Council Laboratory for Molecular Biology in England, and the Salk Institute. I came to Brown in 1972.

Institutions

Bu

Research Description

Professor Knopf received his B.Sc. (Physics) in 1958 at MIT and continued at MIT for his Ph.D. (Biophysics) in 1962 under the mentorship of Dr. Howard Dintzis in the laboratory of Dr. Alex Rich. After a 2-year NIH-sponsored postdoctoral fellowship appointment at the MRC Laboratory of Molecular Biology, Cambridge, England, in the research group of Dr. Francis Crick (who was honored with the Nobel Prize in 1962), Dr. Knopf spent 8 years (1964-1972) at The Salk Institute for Biological Studies, working as a postdoctoral fellow in the laboratory of Dr. Edwin Lennox and being 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. Professor Knopf ascended the academic ladder, earning tenure in 1975, full Professor in 1978, and being named in 1992 as 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 Prof. Knopf was honored as "Teacher of the Year" (Life Sciences, Brown University) for his teaching undergraduate courses in Immunology. He currently holds the title of C.A. & H.B. Stuart Emeritus Professor of Medical Science.

Among his research awards, he has received an Alexander von Humboldt Foundation travel grant to conduct research at Max-Planck-Institute fur Molekular Genetik, Dr. Fritz Melchers' lab, Berlin, Germany (1969); a Fulbright Fellowship (1978-1979) to conduct research in Dr. Graham F. Mitchell's lab, Melbourne, Australia; and a Fogarty Fellowship (1986-1987) for research in Dr. Diane McLaren's lab, London, England, and Dr. Donato Cioli's lab, Rome, Italy. He maintained continuous grant support from 1966-2001 for his research from NIH-NIAID, 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).

Professor 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; immune privilege in the brain; behavioral changes induced in rats by micro-infusion of antibodies to brain cell proteins. Among his major contributions are:

  1. Co-discovery (and naming) of polyribosomes (or polysomes, for short) as the functional unit in hemoglobin synthesis in rabbit reticulocytes.

  2. Development and first reporting of the reticulocyte lysate cell-free protein synthesizing system plus using exogenous mRNA as the template.

  3. 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 intacellular process leading to secretion and surface localization of IgG.

  4. 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.

  5. 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.

  6. 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.

  7. 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 then exposing such immunized rats to a standard EAE challenge.

  8. Demonstrating that micro-infusion of antibodies behind an intact BBB cross-reactive with brain cell antigens can lead to behavioral changes on locomotive activity.

  9. Investigating the possible role of complement fragment C3d as the source of co-signal 2 in the primary humoral immune response that stimulates naive B cells to multiply and differentiate.

Grants and Awards

1959-1964 Pre-doctoral and Post-doctoral Fellowships (PHS)

1967-1972 Research Career Development Award (PHS)

1969 Alexander von Humboldt Stiftung (Travel Award)
Summer Appt.: Dr. Fritz Melchers, Immunol. Unit.
Max-Planck-Inst. fur Molekular Genetik, Berlin, Germany

1978-1979 Senior Scholar Award (Fullbright-Hays)
Sabbatical Appointment: Dr. Graham F. Mitchell,
Immunoparasit. Unit, The Walter & Eliza Hall Inst.,
Melbourne, Australia

1984 Summer Faculty Award (ASEE/Navy Fellowship)
Summer Appt.: Dr. David Dean, Schistosomiasis
Branch Naval Medical Research Inst., Bethesda, MD

1986-1987 Senior International Fellowship (Fogarty Foundation)
Sabbatical Appt.: Dr. Diane J. McLaren, Division of
Parasitology National Inst. for Medical Research,
Mill Hill, London, England, Visiting Scientist

1987 Laboratrio di Biologia Cellulare, Rome, Italy

1991 Schistosomiasis Research Lab: Dr. David Dean
Naval Medical Research Unit #3, Cairo, Egypt

1992 Charles A. & Helen B. Stuart Professor of Medical
Science

1998 Teacher of the Year (Life Sciences, Brown Univ.)

2001 Visiting Scientist
- Cancer Research Unit: Dr. Robert Hyman, The Salk Institute, La Jolla, CA
- Emory Vaccine Center: Dr. Rafi Ahmed, Emory Univ., Atlanta, GA
- Immunology Dept.: Dr. Jack Hay, Univ. of Toronto, Toronto, Canada

2006 Certificate of Appreciation "Emeritus Award"
acknowledging Contributions to Clinical Teaching

Affiliations

- American Association for Immunology
- American Society of Tropical Medicine and Hygiene
- American Association for the Advancement of Science
- American Society for Microbiology
- New England Association for Parasitology

Funded Research

N/A

Teaching Experience

In over 30 years at Brown University, I have taught courses in several areas and have received an Outstanding Teacher Award. The course for which I am most recognized is Principles of Immunology, which has had several course numbers in its evolution from a 100-level course to its current number Bio53. In addition I have taught Bio 160, Vaccine Development for many years, plus a variety of 200-level advanced immunology courses, mostly immunoparasitology. I was initially the instructor of the Immunology section of the Medical Microbiology course, Bio 158, for the pre-med and PLME medical students (1972-1986).
Other courses in which I have played a major role, before formation of the MMI Dept., were Molecular Biology, Biochemistry, and General Biology.

Selected Publications

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