Melanie A. Felmlee, PhD
William K. Chan, PharmD, PhD
Receiving a National Institutes of Health (NIH) grant provides more than funding; the grant enhances and elevates the research. Two NIH grant-funded research projects are currently underway at the Thomas J. Long School of Pharmacy.
Melanie A. Felmlee, PhD, assistant professor of pharmaceutics and medicinal chemistry, received a four-year $1.15 million grant from the NIH Support of Competitive Research (SCORE) Program for her project “GHB Toxicokinetics: Role of sex hormone dependent monocarboxylate transporter regulation and potential for altered overdose risk in transgender men and women.” This SCORE Research Advancement Award is co-funded by the National Institute of General Medical Sciences and the National Institute on Drug Abuse.
William K. Chan, PharmD, PhD, professor and chair of the Department of Pharmaceutics and Medicinal Chemistry, received a $382,000 NIH R15 grant for the proposal “Investigating the molecular mechanisms in controlling the aryl hydrocarbon receptor protein levels.”
NIH grants expand possibilities and allow for creativity. “We are able to design and perform experiments that are optimal to test our hypothesis based on their suitability instead of availability,” said doctor of philosophy student Yujie Yang ’20, one of Dr. Chan’s research assistants. Fellow PhD student Michael Ng ’20, who assists with Dr. Felmlee’s research, agreed. “The grant offers our lab a tremendous boost in our continued mission of studying drug transporters and health outcomes,” Ng said.
Dr. Felmlee’s research focuses on the differences in the way males and females process GHB, or gamma-hydroxybutyrate. Her research on GHB suggests females are protected from toxicity, compared to males, because of the hormones estrogen and progesterone. Her team will study specific proteins that transport GHB across cell membranes and their regulation by sex hormone therapy.
Pharmaceutical and Chemical Sciences Program graduate student Hao “Wendy” Wei ’23 has been very involved with Dr. Felmlee’s research. Wei said the NIH grant represents years of dedicated, persistent research and is built upon the team’s prior findings. “It is the promising results we got in the previous project that led to further studies we are currentlyfocusing on,” Wei said.
Only limited data is available today regarding the effect of hormones on toxicity. “What my graduate research assistants and I have found is females at certain times in their reproductive cycle are more protected from GHB toxicity and they were able to remove the drug faster,” Dr. Felmlee said. “The transporters are the key to figuring out why there are the differences associated with the sex hormones.”
Dr. Chan and his research team are interested in the regulatory mechanisms that control the aryl hydrocarbon receptor (AHR) protein levels in human cells. In 2014, Dr. Chan received a $367,000 NIH grant; his current NIH grant allows him to continue his research on AHR. “The function of the aryl hydrocarbon receptor is essential in response to environmental pollutants and normal cellular processes,” he said.
At Pacific, students have the opportunity to work alongside faculty members on cutting-edge research. Recent graduate Kyra Gong ’20, PharmD assisted with research in Dr. Chan’s lab starting as a pre-pharmacy student. In addition to technical skills, she gained experience collaborating with an interprofessional team. “Instead of always having a correct answer in front of me, I have been trained to think creatively and critically in order to figure out a solution,” Dr. Gong said. “I carry these skills with me today and onward as I become a practicing pharmacist.”
“We hope that by understanding better how this protein is regulated in cells, we can provide more possibilities on targeting this protein and curing diseases.”
Both research initiatives have the potential for broader application. The monocarboxylate transporters Dr. Felmlee and her team study are involved in targeted therapeutic strategies for oncology, fertility studies and immune suppression. “We hope one day our studies can act as a foundation for future drug transporter research in clinically understudied or underserved populations,” said Ng.
The aryl hydrocarbon receptor is involved in cancer, autoimmune diseases, lung diseases and diabetes. A greater understanding of AHR protein levels can contribute to future drug development. “We hope that by better understanding how this protein is regulated in cells, we can provide more possibilities on targeting this protein and curing diseases,” Yang said.
By Anne Marie H. Bergthold