(ATHENS, Ohio – Jan. 29, 2015) When Felicia Nowak, M.D., Ph.D.,
first discovered Porf-2, a previously unknown gene, she knew she had
found an important puzzle piece to understanding the developing
brain. What she would later learn is that the gene may also be
pivotal in the development of novel approaches to treat tumor
growth, neurodegenerative diseases and diabetes complications.
Twenty years ago while creating a cDNA library of a rat’s
hypothalamus, she isolated the gene she called Pre-Optic Regulatory
Factor 2. Since then, Nowak, an associate professor of molecular
endocrinology at the Ohio University Heritage College of Osteopathic
Medicine, and her students have been experimenting with the gene to
better understand how it functions.
Nowak found that Porf-2, which has now been sequenced in human
and mouse genomes, plays a critical role in a form of programmed
cell death known as apoptosis, sometimes called cellular suicide. In
our bodies, cells routinely undergo a cycle of growth and death,
when old or broken cells die and new cells are created to take their
place. Apoptosis is the body’s way of removing aged or unnecessary
“Basically, the cell is programmed to self-destruct,” said Nowak.
“It is a very important part of normal development and a very
important part of maintaining a healthy organ. So, if a cell
decides, ‘hmmm … I don’t feel too good; I’m gonna check out,’ that
leaves room for another healthy cell to take over that space. This
goes on all the time.”
Apoptosis is a self-regulating, complex chemical process set into
motion by numerous factors. Within the body are forces that promote
cell death as well as forces that tell cells to live. The most
dominant voice determines the outcome. Sometimes, the cell renewal
function stops working correctly. In the case of cancer, cells split
wildly out of control and tumors form. For other diseases, cells die
but aren’t replaced with healthy new cells. Scientists like Nowak
are looking for ways to control the process when it malfunctions.
Nowak has been investigating Porf-2 to see if it also has a role
in cell proliferation. Studies strongly suggest that the answer is
yes. Porf-2 not only promotes apoptosis; it also slows down the cell
cycle that drives the formation of new cells. Porf-2 appears to act
like a switch that activates or inactivates enzymes (GTPases) that
regulate cell replication, differentiation and death. What she found
is of profound importance to those studying malignancies of the
central nervous system as well as those in the burgeoning field of
regenerative medicine. Her discovery has sparked interest among a
number of scientists, several of whom have requested her Porf-2
antibodies for their own labs.
recently published book chapter in the multi-volume series “Stem
Cells and Cancer Stem Cells: Therapeutic Applications in Disease and
Injury,” Nowak reviews the work that has been done to date on
Porf-2. In the chapter, Nowak highlights how promising the discovery
of Porf-2 could be in the treatment of many diseases.
“Research like that being done by Dr. Nowak strengthens our
ability to advance the practice of evidence-based medicine and may
radically alter how some diseases will be treated in the future,”
said Heritage College Executive Dean Kenneth H. Johnson, D.O.
“The possibilities from a health standpoint are enormous,” said
Nowak. “If you could control Porf-2, then theoretically you could
stop or slow down the loss of neurons in a specific area. The
pro-apoptotic and anti-proliferative functions of Porf-2 make it a
candidate to play a role in cancer treatment and tumor suppression.
The power of this approach is that specific targeting can be done to
decrease the risks.”
Porf-2 may also play a role in diabetes. Nowak found that insulin
decreases the levels of Porf-2. “This makes sense, as insulin not
only lowers blood sugar by promoting the uptake and metabolism of
glucose by cells in our bodies; it also acts as a very powerful
growth factor,” said Nowak. “In diabetes, when insulin is absent or
ineffective, the pro-apoptotic Porf-2 would be expected to
increase.” Nowak’s lab has shown this to happen in the kidneys of
untreated diabetic rats.
Nowak hasn’t finished her investigation of Porf-2. She is
currently seeking funding from the National Institutes of Health to
continue her work. Nowak’s next step will be to engineer a Porf-2
“knock-out” mouse. By examining an animal without Porf-2 expression,
she will be able to better understand its function in growth and
Nowak’s research has been funded by the Diabetes Institute at
Ohio University and the Ohio University Neuroscience Program.