Hunting the mystery of hepatitis C
June 11--It would be going too far to say Cara Pager is fond of the hepatitis C virus.
But the University at Albany researcher is certainly fascinated by HCV. When she talks about how the virus takes up residence in a cell, maneuvers its way into new quarters or morphs to evade the body's immune response, she smiles and her eyes light up with intellectual curiosity.
"Viruses are absolutely amazing," she said. "How they manipulate cells is awe-inspiring."
But make no mistake. Pager's preoccupation with HCV is like that of a police detective trying to get inside the mind of a criminal. She wants to understand it better so she can predict its moves and stop it in its tracks.
Pager, who came to UAlbany in September, is the lead investigator on a project at the school's RNA Institute that seeks to understand the relationship between HCV and a protein known as RCK, which the virus may need to survive or reproduce. In healthy cells, RCK is important in regulating RNA, or ribonucleic acid, which carries genetic information.
Understanding the connection between HCV and RCK may provide the key to treating or even preventing hepatitis C, which affects 3.2 million Americans and can cause cirrhosis or liver cancer, according to the U.S. Centers for Disease Control and Prevention. The promise of Pager's research has been recognized by the American Association for the Study of Liver Diseases and the American Liver Foundation, which awarded her a three-year, $225,000 Liver Scholars Award.
The hepatitis C virus seems to require RCK for some purpose, possibly to grow. In a healthy cell, RCK can be found in various places. But if hepatitis C is present, RCK is sure to be right there with it, in the fat globules the virus uses like scaffolding to support its development, Pager said. She and her team are trying to answer: Why is the virus taking this specific protein to its own building sites inside the cell?
"We don't know how the virus is doing this and we don't know why the virus is doing this," Pager said.
Finding the answers could lead to new therapies to combat HCV. Because RCK is essential to healthy RNA growth, it's not as simple as looking for a way to knock the protein out, Pager said. But if HCV needs RCK, then blocking their hookup could prevent the virus from growing. Or it could be, once RCK's function is understood better, people would do fine without it for a short time, in order to thwart the virus.
Dr. Peter Ells of Albany Medical Center, a mentor to Pager, said the research may answer mysteries that have troubled doctors for decades. Most people who get hepatitis C end up with a chronic condition that is not easily treated, he said.
"It may unlock the answer as to why, when you get infected with this, we can't cure it," Ells said of Pager's research.
New treatments for hepatitis C are much needed, Ells said. Patients react to current drug treatments much the same way they respond to chemotherapy, although the medications work differently, he said. Patients must take the drugs for six months to a year, they can get side effects like anorexia and depression, and in the end, the drugs don't always work.
"It can be tough therapy," Ells said.
In her lab, Pager works with three assistants. The simplest kind of work they do is to watch cells to see how HCV functions, looking through microscopes with a substance that makes the virus fluoresce.
They also work with RCK a bit, adding agents to make the protein overactive or underactive, and then watch to see how that affects HCV. One question the researchers are looking into is how RCK reacts with HCV RNA, which is essential to the virus' replication. The virus consists of one strand of genes, Pager explained. When it duplicates, it makes a template, or mold of that strand. Does it need RCK to make that duplication work somehow?
One technique researchers use is to lay the innards of a cell infected with HCV onto a synthetic membrane with an opposite charge to the virus. Then researchers isolate parts of the virus RNA, and introduce one of the RCK proteins they have cloned for this purpose.
Because hepatitis C is transmitted through blood, Pager said that as long as she doesn't cut herself, she has virtually no risk of infection. Sharp implements are kept out of work space, which she keeps immaculately neat.
"It's a great virus to work with," Pager said.
She and her team conduct their research at the UAlbany RNA Institute, where officials will dedicate a 15,000-square-foot expansion Tuesday. Pager said in other academic settings, she'd likely work in the microbiology department. But she was drawn to the possibility of being around some 60 other scientists working on RNA research.
"I'm no longer just thinking about the virus, I'm thinking about the RNA. It's a much broader perspective," she said. "The primary reason I'm so excited about being here is it challenges me to think about things differently and use technology that I might not normally be exposed to."
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