Engineers Receive $2 Million NIH Grant To
Develop New Toxicology Tests
Jonathan Dordick |
Chemicals in pharmaceutical drugs can obviously save lives.
But as more and stronger chemicals have been introduced, our
basic knowledge of the broader health impact of all these
chemicals has not kept up with the rapid pace of innovation.
There is exceptionally little information on how chemicals in
our drugs and also in the environment around us, including on
the food we eat, impact some of the most important cells in our
body: stem cells. Without basic knowledge and tests on the
impact of chemicals on our stem cells, we may be unwittingly
damaging essential regenerative functions in our body.
Bioengineers at Rensselaer Polytechnic
Institute and the University of
California, Berkeley, have been awarded a more than $2
million grant from the National Institutes of
Health (NIH) to study how chemicals in drugs and our
environment impact our stem cells.
Leading the research effort for Rensselaer is Jonathan Dordick,
director of the Center for Biotechnology and
Interdisciplinary Studies (CBIS) and the Howard P. Isermann
’42 Professor of Chemical and Biological Engineering. Dordick
is co-principal investigator on the grant with David
Schaffer, professor of chemical and biomolecular
engineering and co-director of the Berkeley Stem Cell Center at
the University of California, Berkeley.
The researchers hypothesize that stem cells, which are
essential for the replacement of dead and damaged tissues in
the body, react in fundamentally different ways to chemicals
than other cells in the body. The grant will allow them to
study the impacts of known chemical compounds on adult stem
cells, providing the most substantive information to date on
how many of the chemicals used every day around the world in
drugs, pesticides, and other products impact stem cells. The
work also will seek to develop a new predictive safety
screening tool that manufacturers can use to test the toxicity
of new chemical compounds on stem cells before their drug or
other product reaches the market. The test will be done without
the use of animals and at speeds far faster than current
tests.
“When you look at the toxicity of drugs or other chemicals
in our environment, you want to understand the response that
all the different cells in the body have to that compound,”
Dordick said. “Most current toxicity screens used by
manufacturers focus on a narrow range of cell types. Stem cells
typically have not been included, although there is now a
rapidly growing interest in the pharmaceutical industry in
using such cells. This greatly limits our understanding of what
a new drug or chemical will have on the body. Vast amounts of
money are wasted on the failed development process and, more
importantly, people’s health could be unknowingly put at
risk.”
Dordick notes that this paradigm may be proving a reality in
the case of many cancer drugs.
“Chemotherapy is pretty effective at killing cancer cells,
but it also damages other cell types in the process,” he said.
“In fact, when some of these treatments are complete, the
ability of certain organs to regenerate is compromised, which
may be due to selective damage to such organs’ stem cells. With
this grant, we hope to better understand this to help weigh the
pros and cons of different treatments.”
To perform the research, the team will utilize what is known
as lab-on-a-chip technology. The technology allows for the
swift testing of thousands of different chemicals on the
surface of one simple, small chip. The chip used in the work is
similar in appearance to a traditional glass microscope slide.
Its specialized surface includes hundreds of microscale spots
of stem cell cultures. Different chemicals can then be added to
each of these culture spots. The stem cells will then be
analyzed for their reaction. In this manner, hundreds of
different chemicals, including drugs and drug combinations, can
be tested on a single chip. The technology also eliminates the
need for animals in the toxicology testing. The stem cells used
in the study are human adult neural stem cells and adult
mesenchymal stem cells (which are grown in our connective
tissue). The work will provide a baseline of fundamental
knowledge on how stem cells are impacted by the chemicals
around us.
The ultimate goal of the research is to develop a
high-throughput and inexpensive system that manufacturers can
use to quickly screen thousands of chemicals for their effects
on stem cells, according to Dordick.
“One of the goals would be that we would add a stem cell
screening component to the safety testing of a pharmaceutical
candidate or to the assessment of the health effect of a
chemical in the environment, say on our food,” he said. “This
would give us a much broader understanding of how the human
body will respond to these chemical compounds.”
The work is an extension of Dordick’s previous work
conducted in a long-standing collaboration with Douglas
Clark, the Warren and Katharine Schlinger Distinguished
Professor and Chair, Department of Chemical and Biomolecular
Engineering at the University of California, Berkeley. He is
co-investigator in the current project, to develop inexpensive
high-throughput toxicology tests and reduce the use of animals
in such testing. Information on their previous research can be
found here.
The grant is over a four-year period. Dordick, Schaffer, and
Clark will be joined in the research by Robert Linhardt,
Ann and John H. Broadbent Jr. ’59 Senior Constellation
Professor of Biocatalysis and Metabolic Engineering at
Rensselaer.
