David M. Knipe

David Mahan Knipe is the Higgins Professor of

Education

Knipe was educated at

In 1979, Knipe joined the faculty at Harvard Medical School as an assistant professor of Microbiology and Molecular Genetics and established his own lab to study HSV. He showed that HSV replicates its DNA in defined compartments in the infected cell nucleus.^[10][11] They further showed that the viral genome associated with the nuclear lamina for immediate-early transcription. This work revealed that intranuclear proteins are localized to specific sites to carry out their functions, much as cytoplasmic proteins were known to localize to specific sites. This led to new areas of study of intranuclear compartmentalization of DNA virus replication. Knipe's research has shown that host cell DNA repair and recombination proteins are localized to the viral replication compartments and that some of these inhibit viral replication while some are essential for viral replication.^[12] He discovered the molecular basis of herpes simplex virus lytic and latent infection through the definition of epigenetic regulatory mechanisms in which: viral proteins promote euchromatin modifications on viral chromatin and transcription of lytic genes in epithelial cells; and the viral latency-associated transcript promotes heterochromatin modifications on viral chromatin and silencing of lytic genes in neurons.^[13][14][15] He defined the structure of viral chromatin during latent infection of neurons and the mechanisms by which viral DNA is kept silenced during latent infection.^[16][17][18] He has also defined the cellular proteins that recognize herpesviral DNA in the nucleus and initiate innate signaling and restrict viral gene expression and identified viral proteins that block host innate responses.^{[19][20][21][22]} His work has shown that replication-defective viruses can serve as a genital herpes vaccine and as a vaccine vector—one of these genital herpes vaccines, HSV-529, is the leading candidate in phase I clinical trials.^[9][23][24]

Awards and honors

Knipe has received several honors and awards including:

• National Science Foundation pre-doctoral fellowship (1972–1975)
• Jane Coffin Childs Postdoctoral Fellowship (1976–1978)
• Leukemia Society of America (now Leukemia & Lymphoma Society) Special Fellowship (1978–1980)
• Cancer Research Scholar of American Cancer Society, Massachusetts Division (1978–1980)
• Faculty Research Award, American Cancer Society (1984–1989)
• MERIT (Method to Extend Research in Time) Award, National Cancer Institute (1988–1996)
• Election to Fellowship in the American Academy for Microbiology (2009)
• S. Edward Sulkin Visiting Professor, University of Texas Southwestern Medical Center (2013)
• Harvard Medical School, Division of Medical Sciences Distinguished Faculty Award (2017)
• Member of the U. S. National Academy of Sciences (2021)^[25]

Personal life

Knipe is married to Suzanne Knipe; they have two daughters and four grandchildren.

References