Richard A. Flavell, Ph.D., D.Sc., FRS (Yale Univ.)

Richard A. Flavell, Ph.D., D.Sc., FRS (Yale Univ.)

Butler Seminar Series

Event Date/Location

February 22, 2017 - 12:00 pm
Thomas Laboratory 003

Speaker

  • Photo of Dr. Richard Flavell

    Dr. Richard A. Flavell

    Sterling Professor of Immunobiology
    Howard Hughes Medical Institute Investigator
    Yale School of Medicine

    Dr. Richard Flavell is Sterling Professor of Immunobiology at Yale University School of Medicine, and an Investigator of the Howard Hughes Medical Institute. He received his B.Sc. (Honors) in 1967 and Ph.D. in 1970 in biochemistry from the University of Hull, England, and performed postdoctoral work in Amsterdam (1970-72) with Piet Borst and in Zurich (1972-73) with Charles Weissmann. Before accepting his current position in 1988, Dr. Flavell was first Assistant Professor (equivalent) at the University of Amsterdam (1974-79); then Head of the Laboratory of Gene Structure and Expression at the National Institute for Medical Research, Mill Hill, London (1979-82); and subsequently President and Chief Scientific Officer of Biogen Research Corporation, Cambridge, Massachusetts (1982-88). Dr. Flavell is a fellow of the Royal Society, a member of  EMBO, the National Academy of Sciences as well as the National Academy of Medicine. Dr. Flavell served as the founding Chairman of Yale’s Department of Immunobiology for 28 years, stepping down in early 2016.

    Dr. Flavell is co-discoverer of introns in cellular genes: he showed DNA methylation correlates inversely with, and prevents, gene expression. He was the first to develop reverse genetics as a postdoc and in his own lab continued in this field throughout his career; he is a pioneer and sophisticated practitioner in the use of this approach in vivo to study function. Dr. Flavell’s laboratory studies the molecular and cellular basis of the immune response, particularly as it applies to autoimmune and auto inflammatory diseases. He has published more than 1000 peer reviewed papers and is one of the world’s most cited immunologists.

Topic

Innate Immune Sensing of Genomic Integrity

Genomic instability is a hallmark of cancer, and policing this is therefore essential to life. For this and many other reasons, extensive DNA repair mechanisms are encoded in our genome. All of these require sensing of DNA damage as a prerequisite for action. 

Acute exposure to ionizing radiation induces massive cell death and severe damage to tissues containing actively proliferating cells, including bone marrow and the gastrointestinal tract. However, the cellular and molecular mechanisms underlying this pathology remain controversial. We found that mice deficient in the double-strand DNA (dsDNA) sensor AIM2 are protected from irradiation-induced death. AIM2 mediates caspase-1-dependent death in response to dsDNA breaks caused by ionizing radiation and chemotherapeutic agents. Mechanistically, we found that AIM2 senses radiation-induced DNA damage in the nucleus to mediate inflammasome activation and cell death. Thus AIM2 is a sensor of genomic integrity.

Audience

Free and open to the university community and the public.

Host

Alex Ploss, Department of Molecular Biology