LMP1520 Translational Research in Pathobiology

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LMP1520 Translational Research in Pathobiology

• Peter Dirks
• Program in Developmental and Stem Cell Biology
• Division of Neurosurgery
• Hospital for Sick Children
• University of Toronto
• Peter.dirks_at_sickkids.ca

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Genetic Information
Human disease
Any better than family history alone?
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LMP1520

• Sept 6 Introduction to course by both course
  coordinators
• - Introductory overview of translational research
  (bedside perspective)
• PETER DIRKS
• Sept 13 Introductory overview of translational
  research (bench perspective)
• JEREMYSQUIRE
• Sept 20 - Clinical impact of molecular
  profiling in cancer and other human diseases
• SUE DONE
• Sept 27 - Drug discovery I Cell signaling
  and small molecule inhibitors of disease DWAYNE
  BARBER
• Oct 4 - Drug discovery II Biomarkers and
  clinical trials
• MING TSAO
• Oct 11 - Mid-term exam
• Oct 18- Advanced molecular imaging
• DAVID HEDLEY
• Oct 25 - Stem cell therapies in cancer and
  other human diseases
• PETER DIRKS
• Nov 1 - Regenerative medicine and tissue
  engineering
• MOLLY SHOICHET
• Nov 8 - Bioinformatics and translational
  research
• MICHAEL TAYLOR

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Podcast!
Nature Reviews Cancer September 2007
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Readings

• Identifying and hurdling obstacles to
  translational research. Nature Reviews
  Immunology 777, 2007.
• Nature Reviews Cancer September 2007

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Definition of translational research

• Comes from the explosion in scientific discovery
  and knowledge

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Definition of translational research

• Use of science to improve the quality of life for
  patients
• Relevance of basic research to clinical problems

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Definition of translational research

• Use of science to improve the quality of life for
  patients
• Relevance of basic research to clinical problems
• Integrative research between clinicians and basic
  scientists

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Definition of translational research

• Use of science to improve the quality of life for
  patients
• Relevance of basic research to clinical problems
• Integrative research between clinicians and basic
  scientists
• Research focused on rapid application of basic
  science to patient care

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Definition of translational research

• Practical basic science

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Basic Science
Clinical Research
Translational Research
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Clinical Medicine (Patient Care)
Basic Research (Science)
vs
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Clinical Medicine (Patient Care)
Basic Research (Science)
vs
-different thought processes -different
languages -different cultures -different
goals -different time demands
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Clinical Medicine

• Focus on information
• Expediency, efficiency
• Time constraints
• Fragmentation of time for academic pursuits due
  to patient demands
• Little time left for research thinking
• Patient advocacy
• Ethical issues

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Science

• Quest for understanding normal and abnormal
  function at the organism, organ, cellular,
  molecular levels
• Measured inquiry
• Freedom of thought
• Benefit for human health not immediately obvious
• Career pressures

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Clinical Medicine (Patient Care)
Basic Research (Science)
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Find the relevant questions for science Give
access to patient material
Clinical Medicine (Patient Care)
Basic Research (Science)
Train Clinicians in the scientific method to
achieve valid results
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Whats driving translational research?

• The Public
• Grant Agencies (limited funds)
• Increasing Accountability
• Need to take explosion in new biological
  information and transfer meaning for human health

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Translational Research

• A focus for major institutions in Europe and
  North America
• Eg. Cancer Research Institute, University of
  Cambridge

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What is good translational research?
The Lancet February 2005
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What is good translational research?
PLoS Biology August 2005
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What is good translational research?

• Do genetically engineer models of human disease
  in the mouse accurately reflect the human
  disease?
• Cancer models

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Cancer Models

• Cell lines
• Human tumor xenografts in mice
• Transgenic and knockout mice
• Localize induction by viral injection

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What is good translational research?
September 2007
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What is good translational research?

• Collaborative
• Pure clinicians, clinician scientists, basic
  scientists
• Integration intellectually and physically
• Based on important research question relevant for
  human disease
• Based on the best fundamental research where the
  research model is an accurate reflection of the
  human disease
• Mouse and human tissues studied in parallel
• Basic research is rigorous and reproducible
• Translational research involves modeling in whole
  organisms not just cell lines
• Rigorous evaluation of the preclinical studies in
  animals before testing in humans (biomarkers vs.
  therapy)
• Correct path followed for knowledge transfer
• Ethical at all levels
• Measureable success for patients