Boris-Lawrie, Kathleen

Dr. Boris-Lawrie

Kathleen Boris-Lawrie, PhD

Executive Director, Life Sciences Network
Active Member, Center for Retrovirus Research, Center for RNA Biology, Comprehensive Cancer Center 

Department of Veterinary Biosciences
The Ohio State University
350 Veterinary Medical Academic Building
1900 Coffey Road
Columbus, Ohio 43210
Ph: (614) 292-1392
Ph: (614) 292-8703 (lab)
Fx: (614) 292-6473
boris-lawrie [dot] 1 [at] osu [dot] edu

Education, research training and experience

  • BS in Microbiology; MA in Microbiology, Southern Illinois Univ, Carbondale, IL; Morey Academic Fellow; Graduate Research Fellow
  • PhD in Molecular Genetics, George Washington Univ, Washington D.C.; Hoffman LaRoche Predoctoral fellow;
  • National Institutes of Health Student Research Training Predoctoral Fellow, Laboratory of Molecular Virology, National Cancer Institute, Bethesda, MD
  • Molecular Virology post-doctoral T32 fellow, McArdle Laboratory for Cancer Research, Univ of Wisconsin Medical School, Madison, WI;
  • Research Biologist I, Drug Discovery Group, Lederle Laboratories, American Cyanamid Company, Pearl River, NY
  • Research Biologist II, Antibiotic Genetics Group, Corporate Molecular Biology, Abbott Laboratories, Abbott Park, IL
  • Assistant Professor, Department of Veterinary Biosciences; Department of Molecular Virology, Immunology & Medical Genetics, Ohio State University, Columbus, OH
  • Associate Professor, Departments of Veterinary Biosciences and Molecular Virology, Immunology & Medical Genetics, Ohio State University, Columbus, OH
  • Professor, Department of Veterinary Biosciences; Department of Molecular Virology, Immunology & Medical Genetics, Ohio State University, Columbus, OH

Research Summary

                Our lab team is creative and ambitious. Our thinking is multidisciplinary and hypothesis-based.  Our attitude is collaborative.  In a nutshell, we collect genomic and proteomic data from mammalian cells, and employ genetic, cell biological, biochemical and biophysical strategies to research our hypotheses.  Our purpose is to uncover fundamental concepts governing the biology of cells and viruses in health and disease.  We hope to translate our findings therapeutically to eliminate virally-infected lymphocytes and pre-cancerous cells.

Present collaborators

International: Cestmir Altaner, Slovak Academy of Sciences; Alan Cochrane, University of Toronto, Canada

National Institutes for Health Structural Biology Center for RNA: Leslie Parent, University of Michigan; Xiao Heng, University of Missouri; Mike Summers, Univ Maryland, Baltimore County; Paul Bienasiaz, Rockefeller University

Ohio State University: Jesse Kwiek, Beth Lee, Michael Freitas, College of Medicine; Karin Musier-Forsyth, College of Arts and Sciences; Robert M. Lee, College of Pharmacy

Research Keywords 

Infectious disease; gene expression; etroviruses; post-transcriptional control; translation control; cis-acting RNA elements; RNA binding proteins; RNA helicase; ribonucleoprotein particles (RNPs)

Research Overview

Considering the fundamental discoveries made in studies of retroviruses, an obvious pattern emerges:  Retroviruses open windows to see how cells work.  Beyond discovery, studies at the virus-host interface expose new strategies for diminishing the severity of infections and proliferation of transformed cells.

The genetic basis of cancer, the fundamental principles of DNA transcription and mRNA biogenesis, genetic engineering of vectors for gene transfer; and host-pathogen adaptation in human and animal species, especially since HIV-AIDS, are a few of the lessons learned from molecular retrovirology.

Because retroviruses are dependent on cellular machineries to replicate their small RNA genome, and since their DNA copy assimilates into the chromosomes of any infected cell and all of their biological needs are provided by host cellular machinery, retroviruses provide a fascinating microcosm of cell biology.   

Our laboratory is dedicated to discovering the RNA regulatory mechanisms necessary for retroviruses to co-opt cellular gene expression machineries.  The cell’s posttranscriptional machineries, plus retroviral and cellular nucleic acid substrates, are the raw materials for our investigations.  Genetic tools and genomic, biochemical and biophysical approaches define commonalities between RNA features and have defined specific RNA binding proteins both cells and viruses use to adjust the functional activity of one RNA to meet multiple purposes.  We now know dynamic changes in viruses’ RNPs enable a single RNA sequence to encode mRNA template for translation or storage and viral genome packaged and released in viral particles or cellular vesicles. 

By comparative analysis, we have unveiled stealth ribonucleoprotein complexes that viruses adapt to support their own proliferation.  Functionally, these RNPs are usurped from a cell-protective role to a virus-promoting role.  We are successfully defining which cognate features in cellular RNAs are recapitulated in viral RNAs, and which regulatory interactions are responsible for physiological control of gene expression.  Necessarily, the broadened impact of our research stretches to how defects in mRNA regulatory pathways contribute to cancer and infectious disease.  

Biosketch

An overarching theme of our research is the interface of cellular post-transcriptional mechanisms with retroviruses that cause cancer and AIDS.  

Discovery is where this story begins, of a unique translation activation mechanism that is reserved for retroviruses and a select cohort of cellular mRNAs. By combining genetic and RNA structural analysis with proteomics and biophysical approaches, we discovered a class of cognate RNA elements that tightly regulate whether or not an mRNA is successful as template for protein synthesis.   

Our research elucidated basic amino acid residues in the RNA binding protein intercalate RNA secondary structure at the 5’ end of the transcript, tethering catalytic activity that was triggered by ATP binding.  Like a knife loosening a complicated knot, physical change to the ribonucleoprotein complex yielded a less complex structure that became engaged with scanning ribosomes.  Simply observed by collection at the bottom a sucrose gradient, the RNP is heavy polysomes, capture by mRNA template of many ribosomes.

Historically, a longstanding issue in virology is how a viral RNA genome of 9000 bases proves sufficient to generate a multi-component virion and genomic RNP, with capacity for infection and spread in animal and human populations. The answers have been debated since the 1970’s, and the solution lays in the RNA structures we have shown are magnets to nucleate RNP components responsible for protein synthesis.  

Milestones

Lessons learned by study at the retrovirus-host interface

  • Patented retroviral structural gene vectors
  • Discovered translation control mechanism conferred by retroviruses
  • Elucidated the cellular effector protein and cognate cis-acting responsive elements in the 5’ UTR
  • Solved the secondary structure of the cognate viral RNA element and cellular paralog
  • Defined the molecular basis is DHX9/RNA helicase tethered to cognate viral and cellular mRNAs
  • Quantified DICER suppresses synthesis of HIV-1 virion proteins
  • Defined HIV-1 antagonizes DICER activity and requires the arginine-rich RNA binding domain in Tat
  • Revealed HIV-1 downregulates host protein synthesis due to activating eIF4E inhibitory binding protein
  • Characterized Vpr is necessary and sufficient for downregulation of host translation
  • Discovered the retention of nuclear cap-binding protein provides HIV-1 resistance to eIF4E inhibition
  • Distinguished distinct components of HIV-1 RNPs for protein synthesis and virion biogenesis
  • Revealed unique capacity for reinitiation of translation by the translation RNP of human retroviruses
  • Defined specific nuclear interactions that distinguish a viral RNP for virion biogenesis

By usurping the cell’s gene expression machineries, retroviruses produce a dozen gene products from a single RNA.  Distinctions in the viral RNPs are expected to reveal selectivity to pulling its Achilles’ heel.

Professional Activites

National service and honors (selection of recent)

  • Co-organizer, Retroviruses 2015, Cold Spring Harbor Laboratory, NY, 2015
  • Co-organizer, Workshop on viral models of cellular RNA biology, Syria, VA, 2009 and 2013
  • International Committee on the Taxonomy of Viruses, Retroviruses, 2012 - present
  • Co-organizer, UCI-sponsored West Coast Retrovirus Meeting, October, Palm Springs, CA, 2012
  • Executive Director, Life Sciences Network, Ohio State University, 2011-present
  • Elected Fellow, American Association for Microbiology, 2011
  • Chair, Council for Graduate Studies, Graduate program in Comparative & Veterinary Medicine, 2010-2012
  • State-of-the-Art lecture, American Society for Virology, 28th Annual Meeting at the University of British Columbia, Vancouver, B.C., Canada, 2009
  • Reviewer, NIH Director’s New Innovator Award study sections, 2008-2010
  • David White Endowed Professorship, College of Veterinary Medicine, Ohio State University, 2008-present
  • Permanent Member, NIH Virology B study section, 2007-2011
  • Ad hoc NIH study sections and site visits 2004, 2006, 2007, 2012, 2013, 2014
  • Elected Fellow, American Association for the Advancement of Science, 2007

Ohio State University memberships, present

  • Joint appointment, Department of Molecular Virology, Immunology & Medical Genetics, College of Medicine
  • Active graduate faculty mentor
    • Comparative and Veterinary Medicine graduate program
    • Molecular, Cellular & Developmental Biology interdisciplinary graduate program
    • Biomedical Sciences graduate program
    • Molecular Genetics graduate program
  • Comprehensive Cancer Center, Arthur G. James Cancer Hospital and Richard J. Solove Research Institute
  • Center for Microbial Interface Biology
  • Davis Heart and Lung Institute
  • Center for Retrovirus Research
  • Center for RNA Biology

Administrative service, selected

  • Elected, Executive Committee, College of Veterinary Medicine, 2014-2017
  • Chair, Council for Graduate Studies, Comparative and Veterinary Medicine, 2010-2012, member 2012-2015
  • Chair, Veterinary Biosciences Faculty Advisory Committee, 2006-2010
  • Elected, Veterinary Biosciences Faculty Advisory Committee, 2004-2010
  • Elected, College of Veterinary Medicine Honors and Awards Committee, 2004-2008
  • Appointed, University Research Committee, 2004-2007
  • Elected, University Graduate Research Council, 2001-2007
  • Appointed, University Curriculum Committee, 2001-2003
  • Appointed, Molecular Cellular Developmental Biology Graduate Studies Committee, 1998-2001
  • Elected, Veterinary Biosciences Graduate Studies Committee, 1997-2008, 2009-present

Contributions to didactic education

  • Veterinary Biosciences/Molecular Genetics/Molecular Biochemistry 7880.07, Advanced post-transcriptional control of genes
  • Integrated Biomedical Graduate Program, College of Medicine, Gene regulation core
  • Veterinary Biosciences/Medical Microbiology & Immunology, Viral pathogenesis
  • Veterinary Medicine 540, Cell biology
  • Veterinary Medicine 618, Hemic-Lymphatic
  • Veterinary Biosciences /Pathology 640, Fundamentals of oncology

People in the Lab

 

Post-PhD Trainees

 

Term

Present position

Rick Laguna, PhD

Molecular biology of viral oncogenesis

August 2104 - present

Research Associate 2

 

Gatikrushna Singh, PhD

Dynamic role of viral and cellular proteins in nucleation of HIV-1 RNPs

 

December 2013 - present

Postdoctoral Researcher

Ioana Boeras, PhD

RNA helicase A in HIV-1 RNA translation and packaging

 

June 2012 - present

Postdoctoral Researcher

Amy Hayes, PhD

2008 - 2011

Environmental Health Specialist, Ohio Department of Health, OH

 

Deepali Singh, PhD

2007 -2010

Assistant Professor, Gautam Buddha University, Greater NOIDA, India

 

J. Marcela Hernandez, PhD

2006 - 2010

STEM Diversity Director, College of Arts and Sciences, Ohio State University, OH

 

Tiffiney Hartman, PhD

2003 - 2005

Research Assistant Professor, Fox Chase Cancer Research Institute , PA

 

Andrew Dangel, PhD

2000 - 2002

Research Scientist, Ohio State University Eminent Scholar in Microbiology, Dr. R. Tabita, OH

Graduate Student Mentorship: Primary Advisor

Name, degree

Program

Term

Fellowship or Position

Sarah Fritz, PhD Candidate
Biomedical Sciences

July 2011 - present

Presidential Fellow 2010-2011

Biomedical Sciences Fellow 2011-2013

 

Jonathon Picking MS
Ohio State Biochemistry

2010 - 2012

Howard Hughes Medical Institute Med into Grad Fellow, 2010-2011; Center for RNA Biology Fellow 2011-2012

Amit Sharma, PhD
Molecular Genetics

2007 – 2012

 

Postdoctoral fellow, Fred Hutchinson Cancer Research Institute, Seattle, WA

Wei Jing, MS

Molecular, Cellular, Developmental Biology

2008 -2010

College of Veterinary Medicine, Barber Fellow

Arnaz Ranji, PhD
Molecular Genetics

 

2005 - 2011

Postdoctoral fellow, Northwestern University, Chicago, IL

Shuiming Qian, PhD
Molecular, Cellular, Developmental Biology

2003 - 2009

Assistant Scientist, Univ Wisconsin, Madison, WI

Cheryl Bolinger, PhD
Molecular, Cellular, Developmental Biology

2003 - 2008

Senior DNA/RNA MOD Engineer

Intrexon Corporation, Gaithersburg, MD

Nicole Placek, MS

Molecular, Cellular, Developmental Biology

2002-2006

Science writer/editor, Columbus, OH

Radhakrishna Sura, DVM, MS

Veterinary Biosciences

2002-2004

Veterinary Pathology Specialist, Dow USA

Alper Yilmaz, PhD
Molecular, Cellular, Developmental Biology

2000 – 2007

Assistant Professor, Yildiz Technical University, Istanbul, Turkey

Tiffiney Roberts, PhD
Molecular, Cellular, Developmental Biology

1998 - 2003

Research Assistant Professor, Fox Chase Cancer Research Institute, PA

Stacey Hull, PhD
Molecular, Cellular, Developmental Biology

1997 - 2002

Associate Faculty, Mira Costa College, San Diego, CA

Melinda Butsch, PhD, MPH
Ohio State Biochemistry

1997 - 2002

Assistant Professor, University of Cincinnati Medical School, OH

 

Lab Members who are and have been research interns and staff

  • Alison Mason, present
  • Greeshma Allareddy, present
  • Joey McGill
  • Stephanie Petyna
  • Jennifer Knippenberg
  • Justin Bale
  • Erin Pigott
  • Faith Barbur
  • Emily Vojt
  • Dave Meleason, DVM
  • Kathyrn Chen, MD
  • Jermaine Cornell Byers
  • Jennifer Simpson
  • Jeong Ha, MD
  • Amber McCreary
  • Sae Bom Lee
  • Jennifer Frey, PhD
  • Jessica Kerney
  • Matt Resnick, DVM
  • Katy Beachy, DVM
  • Yalai Wang