College of Pharmacy

A deeper look at College of Pharmacy faculty - Stories from the departments' newsletter BEAVERx. 

Department of Pharmaceutical Sciences 
Department of Pharmacy Practice

Department of Pharmaceutical Sciences

'Master regulator' of skin formation discovered 

EUREKALERT 

CORVALLIS, Ore. Researchers at Oregon State University have found one gene in the human body that appears to be a master regulator for skin development, in research that could help address everything from skin diseases such as eczema or psoriasis to the wrinkling of skin as people age.

Inadequate or loss of expression of this gene, called CTIP2, may play a role in some skin disorders, scientists believe, and understanding the mechanisms of gene action could provide a solution to them.

"We found that CTIP2 is a transcriptional factor that helps control different levels of skin development, including the final phase of a protective barrier formation," said Arup Indra, an OSU assistant professor of pharmacy. "It also seems particularly important in lipid biosynthesis, which is relevant not only to certain skin diseases but also wrinkling and premature skin aging."

The findings of this research, done in collaboration with Mark Leid, OSU professor of pharmacy, were recently published in the Journal of Investigative Dermatology. This work is supported by the National Institutes of Health, which has provided $1.5 million for its continuation.

Skin is actually the largest organ in the human body, and has important functions in protecting people from infection, toxins, microbes and solar radiation. But it's not static skin cells are constantly dying and being replaced by new cells, to the extent that human skin actually renews its surface layers every three to four weeks. Wrinkles, in fact, are a reflection of slower skin regeneration that occurs naturally with aging.

Major advances have been made in recent years in understanding how skin develops in space and time, and in recent breakthroughs scientists learned how to re-program adult skin cells into embryonic stem cells.

"When you think about therapies for skin disease or to address the effects of skin aging, basically you're trying to find ways to modulate the genetic network within cells and make sure they are doing their job," Indra said. "We now believe that CTIP2 might be the regulator that can do that. The next step will be to find ways to affect its expression."

One of the ways that some ancient botanical extracts or other compounds may accomplish their job in helping to rejuvenate skin, Indra said, is by stimulating gene expression. A more complete understanding of skin genetics might allow that process to be done more scientifically, effectively and permanently.

### Editor's Note: A digital image at this URL shows skin from a laboratory mouse that lacks the CTIP2 gene and therefore has incomplete skin development in the bottom image, lacking a protective barrier: http://oregonstate.edu/dept/ncs/photos/CTIP2.JPG 

Gene could allow lab-grown teeth
Story from British Broadcasting Company

Scientists believe they have found a way to grow teeth in the laboratory, a discovery that could put an end to fillings and dentures.
The US team from Oregon have located the gene responsible for the growth of enamel, the hard outer layer of teeth which cannot grow back naturally.
Other scientists are already growing the inner parts of teeth in animals - but they have no hard enamel coatings.
The Proceedings of the National Academy of Sciences work may plug this gap.
Experiments in mice have shown that the gene, a “transcription factor” called Ctip2, has several functions involving immune responses and the development of skin and nerves.
The work at Oregon State University made the link with enamel by studying mice bred to lack Ctip2.
Lead researcher Dr Chrissa Kioussi said: “It’s not unusual for a gene to have multiple functions, but before this we didn’t know what regulated the production of tooth enamel.”
The scientists found that Ctip2 was crucial for the enamel-producing cells, called ameloblasts, to form and work properly.
Dr Kioussi said: “This is the first transcription factor ever found to control the formation and maturation of ameloblasts, which are the cells that secrete enamel.”
Controlling the gene in conjunction with stem-cell technology could make the artificial creation of functional teeth a real possibility.
Alternatively, the knowledge could be used to strengthen existing enamel and repair damaged enamel, cutting decay and the need for fillings.
Dr Kioussi said: “A lot of work would still be needed to bring this to human applications, but it should work. It could be really cool, a whole new approach to dental health.”
Paul Sharpe, an expert on tooth development at the Dental Institute at King’s College London, said: “If you could find some way of growing ameloblasts that make enamel, you could find a way to repair teeth.
“Any gene like this is worth understanding. The more we learn about it the more we can use the information to make biological models of tooth repair.
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Anti-Cancer Compound Found in Beer 

At the Linus Pauling Institute (LPI) and several OSU colleges, some groundbreaking work is being done on the promise of xanthohumol as an anti-cancer compound. Xanthohumol is a flavonoid found
primarily in hops—the main ingredient in beer.
“Xanthohumol is one of the more significant compounds for cancer chemoprevention we have ever studied,” said Fred Stevens, assistant professor of medicinal chemistry and a principal investigator in LPI. “The published literature and research on its properties are just exploding.”
Don’t get your hopes up—drinking beer doesn’t prevent cancer. Levels of this compound in beer are probably too low to have any major health value. But as a possible food supplement, or in foods designed to increase its level, xanthohumol is of considerable interest for everything from preventing prostate or colon cancer to hormone replacement therapy for women.
And don’t look for a “health beer” any time soon. OSU studies of xanthohumol are just beginning.

See the article in the BEAVERx.
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Department of Pharmacy Practice

The pill is less effective in the obese

LA Times, July 14, 2009 By Thomas H. Maugh II
Obese women starting to take the birth control pill should also use an alternative method of contraception for at least 10 days, and perhaps for as long as 20 days because it takes that long for effective levels of the drug to build up in the blood, Oregon researchers reported today. In women of normal weight, such a buildup only requires about five days, they found.

Epidemiological research has suggested that the pill does not work as well in obese women -- those with a body mass index (BMI) higher than 30. For a woman 5 foot, 6 inches tall, that is a weight greater than 190 pounds. Some experts had thought the problem was that the hormones in the pill were selectively deposited in fat cells and didn’t get into the blood stream, but pharmacologist Ganesh Cherala of Oregon State University and his colleagues reported in the journal Contraception that that is not the case. Instead, it simply takes longer for the drug to build up in the blood stream.

The researchers studied 20 women, ages 18 to 35, all healthy and seeking contraception. Ten were of normal weight and 10 had a BMI above 30. The women stayed in the clinic for 48 hours at the beginning and end of the birth control cycle and blood levels of reproductive hormones were measured during those periods and twice per week on an outpatient basis.

They found that the drugs took an average of about five days to achieve their maximum levels in the women of normal weight, but an average of 10 days in the heavier women. Some took even longer -- one woman took more than 20 days. The situation can be further complicated, the team noted, because many physicians prescribe lower-than-normal doses of the pill to obese women in an effort to reduce their risk of developing venous thrombosis -- blood clots in their legs and elsewhere that can increase the risk of heart attack and stroke.

Dr. Alison Edelman of the Oregon Health and Science University, senior author of the study, cautioned that the team did not study enough women to make definitive clinical recommendations, “other than choosing a contraceptive option that works better for both normal weight women and obese women, like an intrauterine device.”

Source: http://latimesblogs.latimes.com/booster_shots/2009/07/the-pill-is-less-e...

Senior Instructor, Ann Zweber, in a One on One - Story from Terra

“Ann gives me a lot of confidence. She makes me feel I can do whatever I want to do,” George says. “I want to be like her when I’m a pharmacist.”

The mentor Ann Zweber, senior instructor, College of Pharmacy

The student Channa George, second-year pharmacy student from Ten Sleep, Wyoming

Making a difference Take your prescription to the Bi-Mart pharmacy on 9th Street in Corvallis, and you might find Zweber and George working side by side. Zweber works in the pharmacy part time to “maintain my practice and credibility with students,” she says. George is completing an internship as part of the pharmacy program.

George says working with Zweber gives her a role model for how to care for patients, “how she talks to them, listens to them and helps them.” The internship experience also shows how pharmacists are becoming more involved with patients and more responsible for the outcomes of medications.

“Ann gives me a lot of confidence. She makes me feel I can do whatever I want to do,” George says. “I want to be like her when I’m a pharmacist.”

Mental Health Lifeline

Before coming to OSU in 2006, Stacy Ramirez spent 20 years in community pharmacy in a variety of roles, primarily in management and pharmacy operations. Today, in addition to teaching, she works with residents of a mental treatment facility in Corvallis, including Mike Christensen, lower left. (Photos: Karl Maasdam)

The most important visitors to Stacy Ramirez’s office walk around her desk and sit in a chair next to her. As they talk, Ramirez catches subtle clues about her visitors’ emotions, whether or not they are taking their pills or maybe hearing voices again. “I can tell by their eyes if there’s something going on that I need to ask them about,” she says.
Ramirez is a clinical assistant professor in the College of Pharmacy. In addition to teaching classes on pharmacy management and operations, she meets daily with a dozen or more residents at Mid Valley Housing Plus, a residential support facility in Corvallis for people with mental illness. She shares an office with Mid Valley case manager Sam Ortiz where she answers residents’ questions, administers medications—some by court order, others on request—and serves as a liaison with physicians.
No longer focused only on dispensing prescriptions, pharmacists increasingly serve as consultants and sometimes lifelines for people with chronic illness—diabetes, high blood pressure, schizophrenia. The hope is that as specialists in drug effectiveness and interactions, pharmacists can help stabilize lives and reduce hospital visits. For people with mental illness, that includes staying out of jails and homeless shelters.
In collaboration with OSU faculty members Ann Zweber in Pharmacy and Ray Tricker in the Department of Public Health, Ramirez will evaluate the consequences of her work at Mid Valley, documenting impacts on patient quality of life, interactions with police and visits to the emergency room. Just getting started, the research could have broad implications for developing an innovative role for pharmacists in the health care system.
“I have a patient that I see once a week,” says Ramirez, how serves on boards of directors at Mid Valley and the Oregon state Pharmacy Association. “He let me know that he was hearing voices, and the voices were telling him not to take his medications, not to listen to me anymore. So I got a hold of his physician, made some adjustments to his medications, called and checked on him to make sure he was taking them, to see if the voices had come back. He’s doing much better now.
“How that’s hard to quantify. What did that do? Did it save him a hospital trip? Maybe,” she adds.
As a mental health specialist, Tricker served on the Governor of Oregon’s Task Force on Mental Health in Oregon. In 2006, he invited Ramirez to work at Mid Valley. The nonprofit organization now accommodates about 65 clients. Two to three new requests for services—a warm apartment, transportation, counseling, case management (known in mental health circles as an Assertive Community Treatment model)—arrive weekly, says Tricker, who is also on Mid Valley’s board and has worked with the nonprofit organization for more than a decade.
At OSU, he offers students in his public health courses the chance to work with Mid Valley residents. Students gain valuable field experience, assisting residents with everything from shopping to a regular exercise program known as Walking Warriors.
“The goal is to find ways to create conditions that prevent people from relapsing,” Tricker says.
In her meetings with Mid Valley residents, Ramirez sees the need daily. “These patients have multiple psychiatric issues,” she says. “They know that unless they see someone every day, their chances of staying on their medication are not as good.”

See the article in the BEAVERx.