BUFFALO, N.Y. -- University at Buffalo researchers have
identified a new mechanism that plays a central role in adult brain
stem cell development and prompts brain stem cells to differentiate
Their discovery, known as Integrative FGFR1 Signaling (INFS),
has fundamentally challenged the prevailing ideas of how signals
are processed in cells during neuronal development.
The INFS mechanism is considered capable of repopulating
degenerated brain areas, raising possibilities for new treatments
for Parkinson's disease, Alzheimer's disease and other
neurodegenerative disorders, and may be a promising anti-cancer
Michal Stachowiak, Ph.D., director of the Molecular and
Structural Neurobiology and Gene Therapy Program at UB, lead the
research team that discovered INFS.
Results of the research appear in a recent issue of Integrative
Biology at http://xlink.rsc.org/?doi=B902617G.
The approach uses gene engineering and nanoparticles for gene
delivery to activate the INFS mechanism directly and promote
neuronal development. The INFS-targeting gene can prompt these stem
cells to differentiate into neurons.
Stachowiak, UB associate professor of pathology and anatomical
sciences in the UB School of Medicine and Biomedical Sciences, said
the research team set out to see if it is possible to generate a
wave of new neurons from stem cells and direct them to the affected
areas using a mouse model.
"In this way, targeting the INFS potentially could be used to
cure certain brain diseases, particularly in the case of a stroke
or injuries that happen as a single episode and are not
continuously attacking the brain," he said.
"This study provides proof of concept for a novel approach to
the treatment of neuronal loss by means of therapeutic gene
transfer. This is a particularly attractive alternative to
viral-mediated gene transfer.
"The health risks associated with using viruses to carry genes
in this type of gene transfer have led to the search for safer
means of gene delivery," noted Stachowiak. "Nanotechnology offers
an unprecedented advantage in enhancing the efficacy of non-viral
Stachowiak and his wife, Ewa K. Stachowiak, Ph.D., research
assistant professor of pathology and anatomical sciences, along
with their postdoctoral fellows and graduate students, have spent
more than 15 years studying the mechanisms controlling natural
neurogenesis, the creation of new neurons.
Brain injuries, stroke and progressive chronic diseases such as
Parkinson's or Alzheimer's disease result in an extensive loss of
neurons, accompanied by functional deterioration in the affected
brain tissue. Such neurodegenerative diseases are a major health
concern, given the rising aging population worldwide.
In addition, neurodevelopmental disorders, such as autism and
schizophrenia, diminish the production of neurons and disrupt the
brain's cellular structure.
"Manipulation of pre-existing adult stem cells to repopulate
diseased areas of the brain holds the key towards the treatment of
these neurodegenerative and, possibly, neurodevelopmental
disorders," said Michal Stachowiak.
"However, after birth, the ability of the brain's stem cells to
form the necessary new neurons normally is greatly diminished, and
the mechanisms controlling natural neurogenesis are not well
The neurogenic potential of targeting INFS was described
initially in cultured stem cells in vitro by the Stachowiak team.
Following these initial studies, together with a team of UB
chemists that included Indrajit Roy, Ph.D., Dhruba Bharali, Ph.D.,
and Paras N. Prasad, Ph.D., Stachowiak's group investigated the use
of organically modified silica nanoparticles as gene delivery
vehicles into the stem cells of the brain in vivo.
Prasad is executive director of the UB Institute for Lasers,
Photonics and Biophotonics and SUNY Distinguished Professor in the
departments of Chemistry, Physics, Electrical Engineering and
Medicine. Roy is an assistant research professor in the institute;
Bharali was a research associate.
Injae Shin, Ph.D., an expert in genetics at Yonsei University,
Seoul, Korea, in an online article on the Chemical Biology Web
site, called the work "exciting." He noted that it has the
potential to treat neurological diseases, but pointed out the need
for further development of gene delivery methods for the treatment
of neuronal loss.
Stachowiak and colleagues currently are working on such
"Targeting the INFS mechanisms by small molecules could
potentially replace the need for gene transfers and create a
classical drug therapy for the neuronal loss," said Ewa Stachowiak.
"Now that we know the mechanism, we can search effectively for the
means to control it."
Additional contributing authors working at the Molecular and
Structural Neurobiology and Gene Therapy Program are Yu-Wei Lee, a
UB graduate student in pathology and anatomical sciences; Mariolina
Capacchietti, a visiting graduate student from Camerino, Italy; and
John M. Aletta, from CH3 Biosystems LLC, an independent
biotechnology startup company with facilities in UB's New York
State Center of Excellence in Bioinformatics and Life Sciences. The
research was supported by a grant from The John R. Oishei
Foundation to Prasad and Michal Stachowiak, and by grants from the
UB Interdisciplinary Research and Creative Activities Fund and New
York Stem Cell Science (NYSTEM) to Stachowiak.
The University at Buffalo is a premier research-intensive
public university, a flagship institution in the State University
of New York system and its largest and most comprehensive campus.
UB's more than 28,000 students pursue their academic interests
through more than 300 undergraduate, graduate and professional
degree programs. Founded in 1846, the University at Buffalo is a
member of the Association of American Universities.