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 cells.
"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.
In a recently published book chapterr 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 development.
Nowak's research has been funded by the Diabetes Institute at Ohio University and the Ohio University Neuroscience Program.