Located in the heart of the University Hospital’s Cancer
Center, Prof. Sean Morrison’s laboratory is unassuming at
first glance. But among the multitude of computers resting on beige
counters, graduate students and a lone caged mouse, Morrison and
his colleagues have made some significant advances in the
burgeoning field of stem cell research.
- Beth Dykstra
- Morrison
Morrison, a professor of cell and developmental biology, was
recognized for his work earlier this month, when he was flown to
Washington to receive the Presidential Early Career Award for
Scientists and Engineers, presented in a White House ceremony.
The award acknowledges outstanding work by scientists and
engineers starting out their research careers. In Morrison’s
case, the work that led to the award was completed under his first
five-year grant from the National Institutes of Health.
Morrison was happy to receive the award and the recognition that
comes with it.
“It’s nice to get the positive feedback in science,
because oftentimes you work for years and years trying to
accomplish something and along the way, when you’re doing the
work, it’s often hard to tell how impressed people will be
with the end results,” he said.
Omer Yilmaz, a Rackham student working in Morrison’s lab,
shares his sentiment and believes that Morrison is well deserving
of the award.
“All of the projects in the lab are at the cusp of
providing critical insight into the biology of stem cells. Sean,
despite his unrelenting schedule, is always eager to discuss data
and go over experimental details. He never lets any detail escape
his attention,” Yilmaz said.
Some of Morrison’s more prominent work has dealt with the
relationship of stem cells — self-renewing cells which can
give rise to all other kinds of cells in the tissue in which they
are present — and Hirschsprung’s disease, a potentially
fatal birth defect. The disease, which affects one in 4,500
newborns, leads to problems in the enteric nervous system —
the group of neurons that controls the function of the large
intestine.
Previous research had discovered that mutations in two genes
cause Hirschsprung’s. Researchers observed that these
mutations disrupted the signaling pathways corresponding to the
genes, leading to an undeveloped enteric nervous system.
But the specific mechanism through which mutation led to the
disease remained a mystery, until Morrison and his team uncovered
the answer by looking at the source of the enteric nervous system:
stem cells. Using mouse and rat subjects, Morrison found that the
mutations affected the development of the enteric nervous system at
its earliest phase. By stopping the migration of the stem cells
into the lower intestine, the mutation halted the system’s
development.
This discovery opened up the possibility of using stem cells to
treat Hirschsprung’s disease in humans.
“All this raises the question of whether we could treat
human Hirschsprung’s disease by transplanting normal stem
cells into the (lower intestine) of affected babies,” where
they could develop into the missing enteric nervous system,
Morrison said.
However, before any testing on human subjects can be done,
extensive studies must take place using animal specimens. Morrison
and his team are working on transplanting stem cells into the guts
of mice and rats that lack the genes responsible for stem cell
migration. So far, the results are promising.
“We were able to get the stem cells to graft and they did
make neurons,” Morrison said of the transplant. “Now
the question is whether they formed enough neurons. That’s
the next step.”
Currently, Morrison and his lab are continuing their focus on
stem cells by building upon their previous research.
First, they are studying stem cell aging and its affect on the
human aging process.
“As you age, you lose the capacity to repair your tissues
and you increase the chance of getting cancer. We think that may
result from age-related changes in stem cells,” Morrison
said.
Morrison and his team are also looking at the problem of
organogenesis, or how the body makes tissues.
“The problem is, how do you go from a small number of
undifferentiated cells — stem cells — to a complex
three-dimensional organ with different kinds of cells in different
places? We’re interested in how much of the information
required for this is pre-programmed into the stem cells — to
what extent stem cells might have a blueprint when they start the
process of making a tissue,” he said.
Finally, Morrison is looking at the process of stem cell
self-renewal, a subject he has studied extensively. Last year,
Morrison discovered a gene responsible for the self-renewal of stem
cells. His previous work on this subject also contributed greatly
to his receiving the Early Career Award. Now he is looking at
different genes to determine their contribution to the cells’
self-renewal.
Morrison is excited about the future of stem cell research and
the increase in activity it will most likely bring.
“There’s a lot of interest and excitement about the
potential stem cell research has,” he said. “There have
been a tremendous number of new investigators coming into the field
because the questions are so interesting and a lot of people want
to work on them.”