Receptor Tyrosine Kinases Receptor Associated Tyrosine ... · Receptor Tyrosine Kinases Receptor...
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Claudius Mueller, PhD
Transcript of Receptor Tyrosine Kinases Receptor Associated Tyrosine ... · Receptor Tyrosine Kinases Receptor...
ClaudiusMueller, PhD
Hormone therapy
Immunotherapy
Angiogenesis inhibitors
Monoclonal antibodies
Apoptosis inducers
Signal transduction inhibitors
a
b
c
d
a
b
c
d
Signal Transduction
Kinase
Phosphatase
IRS-1
Sos Ras
GDP
GTP
Raf-1
MEK
ERK
ERK
Elk1
Grb2
β
α
PTK
β
α
PTK
(Oda, 2005)Oda, EMBO (2005)
Signal Transduction
(Oda, 2005)Oda, EMBO (2005)
Signal Transduction
Hmm…
Signal Transduction Inhibitor A
Signal Transduction Inhibitor B
Precision Medicine
How do we get from here to there?
How did we get from here to there?
How did we get from here to there?
When did you last see this at your doctor’s office?
Rosalia Lombardo († 1920) Ötzi († 3000 BC)
Preservation matters!
Human Uterus after excision, sitting at room temperature(Espina, 2009)
Protein phosphorylation fluctuates
Paraffin
Block
Diagnostic
Morphology
Equivalent to
Formalin
Immuno-
histochemistry
Equivalent to
Formalin
Extractable
Protein Yield
Equivalent to
Snap-Frozen
Phospho-
proteins
Equivalent to
Snap-Frozen
TheraLin – patented new fixative
Rela
tive M
ean
In
ten
sit
y (
+/-
SE
M)
Fixed phosphoproteins comparable
to snap-frozen mouse liver samples
(Mueller, PlosONE, 2011)
(Mueller, PlosONE, 2011)
Tissue morphology preserved
Being picky is not always bad…
Not all cells in this colon tissue are
tumor cells…
Laser capture microdissection
before after
cap lysis
Laser capture microdissection
Study Setup
Miss-classification of brain cancer patients
Collective “Intelligence”
Smooth Muscle Relaxation
Phosphodiesterase
Smooth Muscle Relaxation
• “UK-92,480” – a phosphodiesterase inhibitor
• Developed for treatment of hypertension.
• In a subsequent human toleration study as a possible drug for angina, some very strange side-effects were noted...
Smooth Muscle Relaxation
Personalized Medicine…
www.wikipedia.com
