Kathleen Boris-Lawrie, PhD

Professor, Department of Veterinary and Biomedical Sciences
Kathleen Boris-Lawrie

Contact

Office Address

235F Animal Science Veterinary Medicine Bldg.
1988 Fitch Avenue
St. Paul, MN 55108
United States

Lab Address

215 Animal Science Veterinary Medicine Bldg.
1988 Fitch Avenue
St. Paul, MN 55108
United States

Titles

Professor, Department of Veterinary and Biomedical Sciences
Faculty, Microbiology, Immunology and Cancer Biology (MICaB) Ph.D. Graduate Program

Education

  • Postdoctoral Fellowship, Molecular Virology, University of Wisconsin School of Medicine
  • PhD, Molecular Genetics, George Washington School of Medicine
  • Predoctoral Fellowship, Lab of Molecular Virology, National Cancer Institute
  • MS and BA, Microbiology, Southern Illinois University

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Biography

Expertise

Retroviruses that cause cancer and AIDS, RNA biology, Host-pathogen interface in health and disease

Awards & recognition

  • Appointed, Director’s Recombinant DNA Advisory Committee, National Institutes of Health (2016-2020)
  • Elected Fellow, American Association for Microbiology, 2011
  • Elected Fellow, Association for the Advancement of Science, 2007
  • Permanent Member, Virology B study section, (2002-2006)

Research summary/interests

By engineering novel viral vectors, we generated unique chimeric structural gene vector systems that were patented and shown to induce efficacious vaccination against bovine leukemia virus infection. By examining properties of the vector RNAs, we uncovered post-transcriptional control elements (PCE) that are conserved in a variety of retroviruses and selected cellular genes, including proto-oncogene junD. Taking a proteomic approach enabled our identification of the PCE effector proteins and the molecular basis for PCE activity requiring DHX9, an RNA helicase. Results of genetics and biochemical approaches demonstrated the PCE-DHX9 interaction recruits retroviral mRNA to polysomes; and this finding is recapitulated in junD and a circumscribed cohort of cellular mRNAs. The evidence posits evolutionary conservation of the PCE RNA regulator at the 5’ terminus of selected RNAs, and convergent adaptation of DHX9 by retroviruses. Site directed mutagenesis and RNA structure mapping enabled us to define the structural context of PCE and the amino acids in DHX9 necessary to form the PCE-DHX9 complex.

A hallmark of infection and other physiologic stresses is downregulation of the cell’s protein synthesis machinery, thus limiting cell growth and triggering innate inflammatory response. We identified for the first-time that HIV-induced cell cycle arrest downregulates cellular translation, and the molecular basis is inhibition of eIF4E activity. Hence, we investigated how HIV and other viruses overt this stress response and characterized novel 4E-independent ribosome scanning, providing cap-dependent synthesis of selected polypeptides. Using computational approaches, we have predicted cognate RNAs and 3-D structural models that are revealing a second level genetic code in the tertiary structure of selected viruses and cellular growth control genes. Our innovative approaches are revealing new appreciation for how cells activate synthesis of polypeptides to recover from stress and molecular mechanisms used by some viruses to overwhelm the innate antiviral response.

Publications

Dr. Boris-Lawrie, Publications