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

The End

cmuelle1@gmu.edu