Horizon eBook - 9

Innovations in Cell-Based Screening * Phenotypic Screens Rise in Popularity

The company's new lab has been working in
parallel with Schlegel's labs for the past six months.
Research on the platform has also been underway
at the NIH and the National Institute of Allergy and
Infectious Diseases, using breast and lung cancer
tumor cells.
Serendipity played a part in developing the
technology, Pollok says. While working with
epithelial cells, Dr. Schlegel noticed that they grew
in colonies, characterized them, and saw that they
took on some of the properties of stem cells without
the kinetic effects often found in some stem cells.
Researchers have reported using the platform and
being able to grow cultures from as few as four cells.
At this point, emphasizes Pollok, the most
exciting application is going on with airway epithelial
cells: "You expand out from biopsies, and when you
take the cells out of the CR media, they redifferentiate,
become polarized and even have beating cilia,
showing that you can take normal cells, grow them,
and put back redifferentiated cells that go back to
their initial state." The platform only works with

| GENengnews.com

epithelial cells, he says.
The CR platform also ensures verifiable
biopsies for cultures. "You tend to get both tumor
and normal cells in biopsies, and both will proliferate,
until normal cell growth can outpace that of cancer
cells," Pollok explains. "Then you need to separate
out normal from tumor cells, or detect them based
on biomarkers. We are using flow cytometry to do
this, determine the functional differences and the
pathway activated in tumors, and then use reporter
The CR platform is faster and less expensive to
use than traditional methods, according to Pollok,
and Propagenix is working not only with airway
epithelial but pancreatic islet cells. Applications
would include culturing for phenotypic screening,
but also personalized tumor chemotyping and,
potentially, cell therapy.
"In theory, the platform could allow one to take
patient-delivered material, grow it out, genetically
engineer it, then use gene editing to correct
problems, and transplant the corrected cells back

in," suggests Pollok. "Partners are looking into to
how they might do just that." At present, the
company seeks discovery research collaborations
with pharma and biopharma companies.
Another basic challenge for phenotypic screening
is developing cell systems relevant to humans in
surrogate creatures. Dr. Vogt and his team at the
University of Pittsburgh have been working with
zebrafish phenotypic screening to develop a
quantitative systems pharmacology approach
that could enable the discovery of new treatments
for acute kidney injury.
The problem with these injuries, he says, is that
they result in the formation of scar tissue, and effects
are often advanced by the time a patient seeks
treatment. Dr. Vogt's team found the zebrafish's
kidney regeneration offered a good model.
They developed a phenotypic platform for
automated imaging of transgenic zebrafish embryos.
Taking advantage of Lim1 homeobox protein Lhx2,
the system uses enhanced green fluorescence protein
EGFP-tagged marker to trace the impact of drugs.


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