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Students in WSU graduate, professional programs contribute to ground-breaking research

SPOKANE, Wash.—Two researchers at Washington State University will be working on a new project aimed to make the drug vigabatrin safer. This is especially important for babies with certain epilepsies, but also if you are a student in WSU’s Doctor of Pharmacy program or looking to pursue a Ph.D. in pharmaceutical sciences.

“The drug vigabatrin remains the one effective therapeutic for the treatment of infantile spasms, a particularly insidious epileptic disorder,” said K. Michael Gibson.

Dr. Jean-Baptiste RoulletDr. K. Michael GibsonDrs. Jean-Baptiste Roullet and Gibson study rare metabolic disorders at the WSU College of Pharmacy. Roullet’s work has predominantly focused on rare disorders of cholesterol metabolism. Gibson has focused on rare disorders of neurotransmitter metabolism, exclusively the inhibitory neurotransmitter Gamma-Amino Butyric acid (GABA).

“We have strongly overlapping areas of investigation and interest,” said Roullet.

Experts in their field

They are both members of the Sterol & Isoprenoid Research (STAIR) Consortium, a national network of researchers dedicated to the investigation of rare or “orphan” genetic disorders.

“In the model of the rare defect of GABA metabolism that we study, we have uncovered new roles for GABA in the control of autophagy and mitophagy, which are essentially recycling processes within the cell that are called upon in times of starvation and/or nutrient deprivation,” Gibson said.

The duo, and other researchers like them, study rare, specific conditions in order to develop targeted therapeutics and to generate translational findings applicable to a larger population.

“In essence, the clinical use of vigabatrin creates a similar situation as we find in our rare genetic diseases of GABA metabolism, namely increased GABA and disrupted autophagy, and this underscores how the study of rare or orphan disorders can have much broader utility,” Gibson said .

Gibson and Roullet just received a $1.58 million grant from the National Eye Institute, part of the National Institutes of Health, and their R01 grant-funded study will run for the next four years at the WSU Health Sciences campus in Spokane.

“Their work could lead to novel insights for disorders such as epilepsy, autism and even addiction. It is truly exciting work,” said John White, Jr., chair of the college’s Department of Pharmacotherapy.

Vigabatrin use can induce irreparable constriction of the visual field when taken regularly beyond about one year. Accordingly, the FDA mandates that bimonthly visual field testing be undertaken for any patient receiving vigabatrin.

Such adverse outcomes of drugs are a major interest to both pharmacists and scientists. A clinical pharmacist must ensure patients and prescribers weigh the benefits of vigabatrin and the risk of visual toxicity of the drug against the irreparable neurologic damage associated with chronic epilepsy in the central nervous system.

“In this context, mitigating this risk with add-on therapeutics, would be an important advance, and an objective actively pursued in this new four-year grant,” Roullet said.

Gibson came to the WSU College of Pharmacy in 2012, and Roullet joined WSU in 2015. Combined, the two scientists have over 70 years of research into rare metabolic disorders under their belts. This is important for prospective graduate students who are looking for experienced faculty mentors to guide them through their Ph.D. studies.

And yes, Gibson and Roullet invite graduate students to consider joining them in research focused on orphan disorders.

How Students Contribute

“Our laboratories, and especially the pioneering work of a previous graduate student and postdoctoral associate, Dr. Kara Vogel, found that drugs which block a specific signaling point in the autophagy pathway could override the effects of GABA on autophagy and mitophagy,” Gibson said. “The identification that GABA, in increased amounts, has an effect in autophagy and mitophagy is a highly significant and novel finding alone.”

Dr. Gibson and Dr. Vogel stand in the research lab at WSU Health Sciences SpokaneVogel completed her Ph.D. in pharmaceutical sciences at WSU in 2014. She published her findings pertinent to vigabatrin in the journal Clinical Pharmacology and Therapeutics.

“Graduate students working in our laboratories could well have a major impact on pharmacotherapy with regard to epilepsy as well as other imbalances in neurotransmitter and steroid metabolism,” Gibson said.

They are also looking for student pharmacists interested in smaller, more targeted research opportunities, or who are participating in the college’s Research Honors Program. Participation in research enables students to see firsthand how to advance knowledge, and enjoy the adventure of discovery.

“Having a research background can help when counseling patients who want to know about specific pathways and how their medications work,” said Darrell Jackson, an associate professor and researcher at the University of Montana and past-speaker in the college’s Preparing For Your Career in Pharmacy seminar series. He spoke to WSU student pharmacists in 2015 on the importance of exposure to research during pharmacy school.

“We previously had a student pharmacist, Tori DeMyer, working on a related project and a current second-year student pharmacist is working on new agents targeting GABA metabolism, in collaboration with Dr. Senthil Natesan,” said Roullet.

Natesan is another pharmacy researcher in Spokane who specializes in computational drug design, pharmacology and medicinal chemistry.

“I cannot think of a more appropriate consideration for the Pharm.D. students than to actively engage in drug discovery, pharmacotherapy and mitigation of drug adverse effects,” Gibson said. “The WSU College of Pharmacy giving consideration to rare diseases within the Pharm.D. curriculum means we are taking steps to prepare our future graduates for the challenges of caring for rare disease patients. With over 7,000 rare diseases affecting more than 30 million individuals in the U.S., this will undoubtedly help the WSU pharmacy program retain its innovative leadership role in training the next generation of pharmacists.”

Providing opportunities for graduate and professional students to contribute in impactful ways to ground-breaking research is part of the college’s mission to develop outstanding health care professionals and scientists through collaborative research and scholarship. It is an example of how WSU provides a transformative student experience and prepares practice-ready graduates who will lead tomorrow’s health care solutions.

More information on the WSU College of Pharmacy degree programs and research can be found online at pharmacy.wsu.edu.

[Lori J. Maricle] 7/31/17]





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