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| | About Ueli Suter |
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Ueli Suter is Professor for Cell Biology at the
Institute of Cell Biology in the Department of Biology of
the ETH Zürich.
Ueli Suter studied Biology II at the Biocenter of the
University of Basel where he also earned his Ph.D. in
1988, working on the Molecular Mechanisms of
Allergies in connection with an industrial dissertation
in the research laboratories of Ciba-Geigy (now
NOVARTIS). Following a brief period at the University
of Montreal in 1989, he moved to Stanford University
Medical School where he became interested in
Molecular and Cellular Neurobiology, in particular in
Neurotrophin Signaling and Processing. In 1993, he
was appointed to the ETH Zürich.
The current focus of the research of Ueli Suter
concerns the fundamental principles of Neuron-Glia
Interactions during the development, differentiation,
maintenance and regeneration of the nervous system,
with a particular emphasis on neurodegenerative
diseases, most notably Neuropathies and Multiple
Sclerosis. His research interests extend further into
Stem Cell Biology and modern methods in Mouse
Genetics.
For publications, see: http://publicationslist.org/ueli.suter
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PROJECT 1: Develop a line of cells which
mimic Schwann cells to use in a high throughput
screen (HTS) to identify treatments for
CMT1A
Principal Investigator: Professor Ueli
Suter, Institute of Cell Biology, ETH Zurich,
Switzerland
The CMTA has begun funding Professor Ueli Suter, who will develop the cells to be
used in the HTS. Professor Suter is uniquely qualified
to perform these experiments. It was he who
first "discovered" PMP22 in 1992 and it is because of
his investigations that we know that over-expression of
PMP22 causes CMT1A. He has great experience in
the cell biology of PMP22 and has extensively studied
PMP22 expression by culturing Schwann cells in
tissue culture wells, a technique that is necessary for
high through-put screening.
Schwann cells are notoriously difficult to grow in
tissue culture in part because they change the amount
of PMP22 and other proteins they make over time. In
addition, it is difficult to measure how much PMP22
protein Schwann cells make without performing labor
and time consuming protein measurements, which
are also a problem for HTS, which requires rapid
measurements to screen high numbers of candidate
medicines.
Therefore, in Project 1, Professor Suter will utilize
a more stable line of cells that are known as "MSC 80"
cells, which were created from Schwann cells by
Professor Anne Baron van Evercooren in France. He
will utilize genetic engineering to cause the MSC80
cells to turn on a protein called luciferase whenever
they would normally turn on PMP22.
Luciferase is the protein used by fireflies to glow;
therefore the cells will emit light every time PMP22 is
expressed The more PMP22 the MSC80 cells
express, the brighter they will glow. This will allow the
robots in the HTS tests described below to simply
measure brightness as a measure of PMP22
levels.
It is essential to generate these cells for the
success of the HTS strategy, but this is not a simple
challenge. It will take 1-2 years to create these MSC80-
luciferase cells to the point that they can be effectively
used in the HTS.
Once the cells have been generated, they will be
used in the HTS facility housed at the NIH Chemical
Genomics Center under the direction of Dr. Jim
Inglese. Using a robotic computerized system, Dr.
Inglese and his colleagues will be able to rapidly test
hundreds of thousands of candidate medications to
determine if they reduce luciferase levels (brightness)
in the MSC80 cells.
Those compounds that reduce luciferase will be
considered to be candidate medications that can
reduce PMP22 levels and they will be submitted for
additional testing in laboratory models of CMT1A.
Those medications that are also successful in
laboratory models will then be considered for clinical
trials in patients with CMT1A.
We are very excited about these projects and hope
to have multiple candidate medications in clinical
trials within the next 3-5 years.
To learn more about the CMTA STAR, please click here.
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