Download Document

NOD 2007-1
•
Capitalizing on what drives biomedical science and scientists?
– Curiosity
– Competition (fame and fortune?)
– Desire to solve a health problem or a disease
•
The approaches
– Fundamental or basic science
– Disease-oriented research
– Translational research
•
Sticking points
– Interdisciplinary training
– Communication between basic and clinical scientists
Philosophy and Goals for the course-2
•
To initiate thinking re: disease mechanisms
•
“ready observer” concept
•
Consider mechanisms across disease boundaries
•
Exposure to a few diseases and clinical material
What it is and is not-3
• It is
– An overview
– A sampler
– A way of thinking about disease mechanisms
• It is not
–
–
–
–
Spoon-fed learning
Comprehensive
An aid for you in writing the first paragraph of a grant
A promotional spot for translational research
Logistics-4
•
Course meeting times
•
“Overviews”, ToolBoxes” and “Clinical Demonstrations”
•
Visiting lecturers/lunches
•
Reading assignments and Website materials
•
Extras
– Movies
– Clinical rounds the last week
•
Assessments and Participation
– Open format
– I want to know if you will not be present
– Special issues around presentations/clinical demonstrations
The “By-Disease” Approach
•
Common for textbooks and courses on this topic
•
Examples
– Gilman textbook - 97 chapters
– NINDS website - 600 listings not counting NIMH, NIDA etc
•
Useful for clinical diagnosis and as reference material
•
Less useful for discovery science as virtually all mechanisms and
themes cross disease boundaries
The theme approach to Neurobiology of Disease-6
1. Cell injury
energy metabolism
mitochondria
oxidative injury
free radicals and metals
2. Cell death
programmed cell death
apoptosis
necrosis
cell cycle proteins, growth control
signaling cascades
3. Protein folding and misfolding
chaperones
aggregation
ubiquitin/proteosome system
The theme approach to Neurobiology of Disease-7
4. Cell signaling and cell-cell interactions
kinases, phosphatases
cell adhesion
neuronal-glial interactions
trophic interactions
5. Development and synaptogenesis
neurogenesis, cell fate determination
migration and lamination
synaptogenesis and synaptic targeting
synaptic dysfunction
circuitry abnormalities
6. Neuroplasticity
adaptive and maladaptive
membrane excitability
reward mechanisms
addiction
HPA-stress axis
The theme approach to Neurobiology of Disease-8
7. Regeneration and repair mechanisms
normal and maladaptive
autoimmune – T,B cell immunity
inflammatory – cytokines, microglia
8. Single genes and disease
single gene disorders, e.g.channelopathies
gene discovery strategies
9. Multigenic disease
genetic susceptibility
transcriptional regulation
gene discovery strategies
animal models and humans
10. Toxins and environmental influences
movement disorders
neurodegeneration
mechanisms of neurotoxins
epigenetics
This year’s themes-9
•
Intro week
– Thematic approach, Bench-Bedside, Clinical Trials
•
Genes and Disease
– This year’s clinical example: Epilepsy
•
Maladaptive plasticity
– This year’s clinical example: Addiction
•
Regeneration and Repair
– This year’s clinical example: MS
•
Neurodegeneration
– This year’s clinical example: Parkinson’s Disease
•
Student Presentations/Clinical Rounds